Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Estudiar y trabajar como factores de riesgo en estudiantes de enfermería, Universidad Nacional Formosa, 2022 / Study and work as risk factors in nursing students, National University of Formosa,2022

Objetivo: Correlacionar la variable principal sostén del hogar con las variables género, edad, horas de trabajo, horas de sueño y factores de riesgo cardiovascular (índice de masa corporal, hipertensión arterial, dislipemia y diabetes mellitus), en estudiantes de 3º, 4 y 5º año de la Licenciatura en Enfermería, Universidad Nacional de Formosa. Metodología: estudio descriptivo, correlacional, transversal realizado en 214 estudiantes, durante el año 2022, utilizándose un cuestionario on-line autoadministrado, estructurado y medición de peso y talla. Resultados: el 76% fueron mujeres; 64%, principal fueron principal sostén del hogar, 57% refirió dormir menos de 6 horas al día, 15 % trabaja más de 41 horas semanales; 67% tuvo respuestas no saludables a la variable estrés, para la variable actividad física este valor ascendió a 71% y el 53,8% presentó exceso de peso. Se encontró asociación significativa entre ser el principal sostén del hogar con exceso de peso, trabajar 41 horas o más semanalmente, dormir menos de 6 horas al día y con la presencia de 3 o más factores de riesgo cardiovascular. Conclusiones: Las condiciones de vida que afrontan los estudiantes que de manera simultánea estudian, trabajan y son principal sostén del hogar pueden generar estrés, el cual es un factor de riesgo para las enfermedades cardiovasculares[AU]

Objetive: to correlate the main variable of primary income earner or primary breadwinner with gender, age, working hours, sleep hours, and cardiovascular disease risk factors (body mass index, hypertension, dyslipidemia, and diabetes mellitus) in 3rd, 4th, and 5th-year nursing students at the Nursing Program at the National University of Formosa. Methodology: The study was a descriptive, correlational, cross-sectional, conducted with 214 students during 2022 using a self-administered structured online questionnaire and measurement of weight and height. Results: 76% were women, 64% were the main breadwinner, 57% reported sleeping less than 6 hours a day, 15% working more than 41 hours per week; 67% had unhealthy responses to the stress variable, this value rose to 71% for the physical activity variable, and 53.8% were overweight. A significant association was found between the main variable of primary breadwinner and being overweight, working 41 or more hours weekly, and the presence of 3 or more cardiovascular risk factors. Conclusions: The living conditions faced by students who simultaneously study and work, and being the main breadwinner in the household can generate stress, which is a risk factor for cardiovascular diseases[AU]

Objetivo:: correlacionar a variável principal de sustento econômico do lar com as variáveis gênero, idade, horas de trabalho, horas de sono e fatores de risco cardiovascular (índice de massa corporal,hipertensão arterial, dislipidemia e diabetes mellitus) em estudantes do 3º, 4º e 5º ano do curso de graduação em Enfermagem, Universidade Nacional de Formosa. Metodologia: O estudo foi descritivo, correlacional e transversal, realizado em 214 estudantes durante o ano de 2022. Foi utilizado um questionário online autoadministrado e estruturado, e a medição de peso e altura dos estudantes foi realizada. Resultados: 76% dos estudantes eram mulheres; 64% eram o principal sustento econômico do lar; 57% relataram dormir menos de 6 horas por dia, 15% responderam que trabalham mais de 41 horas por semana; em relação aos fatores de risco cardiovascular, 67% tiveram respostas não saudáveis para a variável estresse, para a variável atividade física esse valor aumentou para 71% e 53,8% apresentaram excesso de peso. Foi encontrada uma associação significativa entre a variável principal de sustento econômico do lar com as variáveis excesso de peso, trabalhar 41 horas ou mais por semana, dormir menos de 6 horas al día e a presença de 3 ou mais fatores de risco cardiovascular. Conclusões: As condições de vida enfrentadas pelos estudantes que simultaneamente estudam, trabalham e são o principal sustento do lar podem gerar estresse, que é um fator de risco para doenças cardiovasculares[AU]

Social media uses amongst adolescents: motives, minority stress and eudaimonic well-being / Uso de redes sociales en adolescentes: motivación, estrés de minorías y bienestar eudaimónico

Introduction: The scientific evidence regarding the effects of online social media use on the well-being of adolescents is mixed. In gen-eral, passive uses (receiving, viewing content without interacting) and more screen time are related to lower well-being when compared with active uses (direct interactions and interpersonal exchanges). Objectives:This study ex-amines the types and motives for social media usage amongst adolescents, differentiating them by gender identity and sexual orientation, as well as its effects on eudaimonic well-being and minority stress. Method: A cross-sectional study was conducted with 1259 adolescents, aged 14 to 19 (M= 16.19; SD= 1.08), analysing the Scale of Motives for Using Social Net-working Sites, eudaimonic well-being, the Sexual Minority Adolescent Stress Inventory, screen time and profile type. Results:The results found that longer use time is related to finding partners, social connection and friendships; that gay and bisexual (GB) adolescents perceive more distal stressors online;and that females have higher levels of well-being. Discus-sion: The public profiles of GB males increase self-expression, although minority stress can be related to discrimination, rejection or exclusion. Dif-ferentiated socialization may contribute to a higher level of well-being in females, with both active and passive uses positively effecting eudaimonic well-being in adolescents.(AU)

Introduction: The scientific evidence regarding the effects of online social media use on the well-being of adolescents is mixed. In general, passive uses (receiving, viewing content without interacting) and more screen time are related to lower well-being when compared with active uses (direct interactions and interpersonal exchanges). Objectives: This study examines the types and motives for social media usage amongst adolescents, differentiating them by gender identity and sexual orientation, as well as its effects on eudaimonic well-being and minority stress. Method: A cross-sectional study was conducted with 1259 adolescents, aged 14 to 19 (M = 16.19; SD = 1.08), analysing the Scale of Motives for Using Social Networking Sites, eudaimonic well-being, the Sexual Minority Adolescent Stress Inventory, screen time and profile type. Results: The results found that longer use time is related to finding partners, social connection and friendships; that gay and bisexual (GB) adolescents perceive more distal stressors online; and that females have higher levels of well-being. Discussion: The public profiles of GB males increase self-expression, although minority stress can be related to discrimination, rejection or exclusion. Differentiated socialization may contribute to a higher level of well-being in females, with both active and passive uses positively effecting eudaimonic well-being in adolescents.(AU)

Firefighter uncompensable heat stress results in excessive upper body temperatures measured by infrared thermography: Implications for cooling strategies.

This research sought to evaluate the thermal zones of the upper body and firefighter personal protective equipment (PPE) immediately following uncompensable heat stress (0.03 °C increase/min). We hypothesized that the frontal portion of the head and the inside of the firefighter helmet would be the hottest as measured by infrared thermography. This hypothesis was due to previous research demonstrating that the head accounts for ∼8-10% of the body surface area, but it accounts for ∼20% of the overall body heat dissipation during moderate exercise. Twenty participants performed a 21-min graded treadmill exercise protocol (Altered Modified Naughton) in an environmental chamber (35 °C, 50 % humidity) in firefighter PPE. The body areas analyzed were the frontal area of the head, chest, abdomen, arm, neck, upper back, and lower back. The areas of the PPE that were analyzed were the inside of the helmet and the jacket. The hottest areas of the body post-exercise were the frontal area of the head (mean: 37.3 ± 0.4 °C), chest (mean: 37.5 ± 0.3 °C), and upper back (mean: 37.3 ± 0.4 °C). The coldest area of the upper body was the abdomen (mean: 36.1 ± 0.4 °C). The peak temperature of the inside of the helmet increased (p < 0.001) by 9.8 °C from 27.7 ± 1.6 °C to 37.4 ± 0.7 °C, and the inside of the jacket increased (p < 0.001) by 7.3 °C from 29.2 ± 1.7 °C to 36.5 ± 0.4 °C. The results of this study are relevant for cooling strategies for firefighters.

New opportunities for antioxidants in amelioration of neurodegenerative diseases.

This comprehensive review elucidates the critical role of antioxidants to mitigate oxidative stress, a common denominator in an array of neurodegenerative disorders. Oxidative stress-induced damage has been linked to the development of diseases such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. This article examines a wide range of scientific literature and methodically delineates the several methods by which antioxidants exercise their neuroprotective benefits. It also explores into the complex relationship between oxidative stress and neuroinflammation, focusing on how antioxidants can alter signaling pathways and transcription factors to slow neurodegenerative processes. Key antioxidants, such as vitamins C and E, glutathione, and polyphenolic compounds, are tested for their ability to combat reactive oxygen and nitrogen species. The dual character of antioxidants, which operate as both direct free radical scavengers and regulators of cellular redox homeostasis, is investigated in terms of therapeutic potential. Furthermore, the study focuses on new antioxidant-based therapy techniques and their mechanisms including Nrf-2, PCG1α, Thioredoxin etc., which range from dietary interventions to targeted antioxidant molecules. Insights into ongoing clinical studies evaluating antioxidant therapies in neurodegenerative illnesses offer an insight into the translational potential of antioxidant research. Finally, this review summarizes our present understanding of antioxidant processes in neurodegenerative illnesses, providing important possibilities for future study and treatment development.

The circular RNA circSLC16A10 alleviates diabetic retinopathy by improving mitochondrial function via the miR-761-5p/MFN2 axis.

It has been demonstrated that circular RNAs (circRNAs) are associated with the development of diabetic retinopathy (DR). Nevertheless, the function of circSLC16A10 in the development of DR remains unclear. In order to investigate the role of circSLC16A10, we employed cell and animal models of DR. An analysis of a public database revealed that hsa_circSLC16A10 was expressed at lower levels in DR patients than in diabetic patients without DR or healthy controls. Additionally, the level of hsa_circSLC16A10 was lower in high glucose (HG)-exposed ARPE-19 cells and diabetic mice. hsa_circSLC16A10 was observed to be mainly distributed in the cytoplasm. Moreover, overexpression of hsa_circSLC16A10 alleviated HG-induced endoplasmic reticulum stress and cell apoptosis in vitro. Furthermore, overexpression of hsa_circSLC16A10 ameliorated HG-induced mitochondrial dysfunction, as evidenced by improvements in mitochondrial structure and function. hsa_circSLC16A10 acted as a hsa-miR-761-5p sponge to increase MFN2 expression. MFN2 knockdown or hsa-miR-761-5p overexpression partially reversed the protective effect of hsa_circSLC16A10 in vitro. The protective effect of mmu_circSLC16A10 against DR was confirmed in an animal model of DR. These findings indicate that circSLC16A10 may regulate DR progression by improving mitochondrial function via the miR-761-5p/MFN2 axis.

Measurement of cellular MDA content through MTBE-extraction based TBA assay by eliminating cellular interferences.

Malondialdehyde (MDA) has long been served as a crucial indicator for assessing cellular oxidative stress levels. In this study, we introduce a new approach to determine cellular MDA levels based on a methyl tert-butyl ether (MTBE) extraction, aimed at eliminating interferences from cellular components during thiobarbituric acid (TBA) derivatization of MDA. By leveraging the effective MTBE extraction, we identified that the determination of the MDA-TBA adduct formed from the MTBE extraction layer can effectively eliminate the interferences from cellular proteins and metabolites. This method demonstrated acceptable linearity and precision in cellular samples and showed significant differences in H2O2 treated cellular oxidative stress models. The MTBE extraction-based MDA-TBA approach provides a reliable, cost-effective, and feasible method to determine cellular MDA levels using batch microplate reader approach for the assessment of cellular oxidative stress.

Increased plasma levels of neuro-related proteins in patients with stress-related exhaustion: A longitudinal study.

Exhaustion disorder (ED) is a stress-related disorder characterized by physical and mental symptoms of exhaustion. Recent data suggest that pathophysiological processes in the central nervous system are involved in the biological mechanisms underlying ED. The aims of this study were to investigate if plasma levels of neuro-related proteins differ between patients with ED and healthy controls, and, if so, to investigate if these differences persist over time. Using the Olink Neuro Exploratory panel, we quantified the plasma levels of 92 neuro-related proteins in 163 ED patients at the time of diagnosis (baseline), 149 patients at long-term follow-up (7-12 years later, median follow-up time 9 years and 5 months), and 100 healthy controls. We found that the plasma levels of 40 proteins were significantly higher in the ED group at baseline compared with the control group. Out of these, the plasma levels of 36 proteins were significantly lower in the ED group at follow-up compared with the same group at baseline and the plasma levels of four proteins did not significantly differ between the groups. At follow-up, the plasma levels of two proteins were significantly lower in the ED group compared with the control group. These data support the hypothesis that pathophysiological processes in the central nervous system are involved in the biological mechanisms underlying ED.

Substrate stress relaxation regulates neural stem cell fate commitment.

Adult neural stem cells (NSCs) reside in the dentate gyrus of the hippocampus, and their capacity to generate neurons and glia plays a role in learning and memory. In addition, neurodegenerative diseases are known to be caused by a loss of neurons and glial cells, resulting in a need to better understand stem cell fate commitment processes. We previously showed that NSC fate commitment toward a neuronal or glial lineage is strongly influenced by extracellular matrix stiffness, a property of elastic materials. However, tissues in vivo are not purely elastic and have varying degrees of viscous character. Relatively little is known about how the viscoelastic properties of the substrate impact NSC fate commitment. Here, we introduce a polyacrylamide-based cell culture platform that incorporates mismatched DNA oligonucleotide-based cross-links as well as covalent cross-links. This platform allows for tunable viscous stress relaxation properties via variation in the number of mismatched base pairs. We find that NSCs exhibit increased astrocytic differentiation as the degree of stress relaxation is increased. Furthermore, culturing NSCs on increasingly stress-relaxing substrates impacts cytoskeletal dynamics by decreasing intracellular actin flow rates and stimulating cyclic activation of the mechanosensitive protein RhoA. Additionally, inhibition of motor-clutch model components such as myosin II and focal adhesion kinase partially or completely reverts cells to lineage distributions observed on elastic substrates. Collectively, our results introduce a unique system for controlling matrix stress relaxation properties and offer insight into how NSCs integrate viscoelastic cues to direct fate commitment.

Constraining Earth's nonlinear mantle viscosity using plate-boundary resolving global inversions.

Variable viscosity in Earth's mantle exerts a fundamental control on mantle convection and plate tectonics, yet rigorously constraining the underlying parameters has remained a challenge. Inverse methods have not been sufficiently robust to handle the severe viscosity gradients and nonlinearities (arising from dislocation creep and plastic failure) while simultaneously resolving the megathrust and bending slabs globally. Using global plate motions as constraints, we overcome these challenges by combining a scalable nonlinear Stokes solver that resolves the key tectonic features with an adjoint-based Bayesian approach. Assuming plate cooling, variations in the thickness of continental lithosphere, slabs, and broad scale lower mantle structure as well as a constant grain size through the bulk of the upper mantle, a good fit to global plate motions is found with a nonlinear upper mantle stress exponent of 2.43 [Formula: see text] 0.25 (mean [Formula: see text] SD). A relatively low yield stress of 151 [Formula: see text] 19 MPa is required for slabs to bend during subduction and transmit a slab pull that generates asymmetrical subduction. The recovered long-term strength of megathrusts (plate interfaces) varies between different subduction zones, with South America having a larger strength and Vanuatu and Central America having lower values with important implications for the stresses driving megathrust earthquakes.

Passion fruit HD-ZIP genes: Characterization, expression variance, and overexpression PeHB31 enhanced drought tolerance via lignin pathway.

The HD-ZIP (homeodomain-leucine zipper) genes hold significant importance in transcriptional regulation, especially in plant development and responses to abiotic stresses. However, a comprehensive study targeting HD-ZIP family members in passion fruit has been absent. In our current research, 34 HD-ZIP family members (PeHBs) were identified by bioinformatics analysis. Transcriptome analysis revealed that PeHBs exhibited distinct expression patterns when subjected to the four different abiotic stresses, and significant differential expression of PeHBs was also found among the three developmental stages of the fruit and between the purple and yellow genotype passion fruit leaves. An integrated metabolome and transcriptome analysis further revealed that the HD-ZIP III class gene PeHB31 (homologous to ATHB8), was co-upexpressed with lignans in yellow fruit P. edulis (commonly used as a resistance rootstock) when compared to purple fruit P. edulis. The transformation of Arabidopsis and yeast with the PeHB31 gene showed an enhancement in their capacity to withstand drought conditions. Notably, the transgenic Arabidopsis plants exhibited an increase in lignin content within the vascular tissues of their stems. This research lays the groundwork for future studies on the control mechanisms of lignin biosynthesis by HD-ZIP genes (especially HD-ZIP classes III and I) involved in drought tolerance.

Endoplasmic reticulum stress as a target for retinoids in cancer treatment.

Retinoids, natural and synthetic derivatives of vitamin A, have various regulatory activities including controlling cellular proliferation, differentiation, and death. Furthermore, they have been used to treat specific cancers with satisfying results. Nevertheless, retinoids have yet to be converted into effective systemic therapies for the majority of tumor types. Regulation of unfolded protein response signaling, and persistent activation of endoplasmic reticulum stress (ER-stress) are promising treatment methods for cancer. The present article reviews the current understanding of how vitamin A and its derivatives may aid to cause ER-stress-activated apoptosis, as well as therapeutic options for exploiting ER-stress for achieving beneficial goal. The therapeutic use of some retinoids discussed in this article was related to decreased disease recurrence and improved therapeutic outcomes via ER-stress activation and promotion, indicating that retinoids may play an important role in cancer treatment and prevention. More research is needed to expand the use of vitamin A derivatives in cancer therapy, either alone or in combination with unfolded protein response inducers.

Effect of cortical bone thickness on shear stress and force in orthodontic miniscrew-bone interface - A finite element analysis.

Miniscrews are widely used in orthodontics as an anchorage device while aligning teeth. Shear stress in the miniscrew-bone interface is an important factor when the miniscrew makes contact with the bone. The objective of this study was to analyze the shear stress and force in the screw-bone interface for varying Cortical Bone Thickness (CBT) using Finite Element Analysis (FEA). Varying CBT of 1.09 mm (1.09CBT) and 2.66 mm (2.66CBT) with miniscrews of Ø1.2 mm, 10 mm length (T1), Ø1.2 mm, 6 mm length (T2) and Ø1.6 mm, 8 mm length (T3) were analyzed. Six Finite Element (FE) models were developed with cortical, cancellous bone, miniscrews and gingiva as a prism. A deflection of 0.1 mm was applied on the neck of the miniscrews at 0°, +30° and -30° angles. The shear stress and force in the screw-bone interface were assessed. The results showed that the CBT affects the shear stress and force in the screw-bone interface region in addition to the screw dimensions and deflection angulations. T1 screw generated lesser shear stress in 1.09CBTand 2.66CBTcompared to T2 and T3 screws. Higher CBT is preferred for better primary stability in shear aspect. Clinically applied forces of 200 gms to 300 gms to an anchorage device induces shear stress in the miniscrew-bone interface region might cause stress shielding. Thus, clinicians need to consider the effect of varying CBT and the size of the miniscrews for the stability, reduced stress shielding and better anchorage during orthodontic treatment.

IbpAB small heat shock proteins are not host factors for bacteriophage ϕX174 replication.

Bacteriophage ϕX174 is a small icosahedral virus of the Microviridae with a rapid replication cycle. Previously, we found that in ϕX174 infections of Escherichia coli, the most highly upregulated host proteins are two small heat shock proteins, IbpA and IbpB, belonging to the HSP20 family, which is a universally conserved group of stress-induced molecular chaperones that prevent irreversible aggregation of proteins. Heat shock proteins were found to protect against ϕX174 lysis, but IbpA/B have not been studied. In this work, we disrupted the ibpA and ibpB genes and measured the effects on ϕX174 replication. We found that in contrast to other E. coli heat shock proteins, they are not necessary for ϕX174 replication; moreover, their absence has no discernible effect on ϕX174 fecundity. These results suggest IbpA/B upregulation is a response to ϕX174 protein expression but does not play a role in phage replication, and they are not Microviridae host factors.

Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats.

OBJECTIVE: The hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. METHODS: Thirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). RESULTS: α-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. CONCLUSION: Resveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.

Use of Microalgae-Derived Astaxanthin to Improve Cytoprotective Capacity in the Ileum of Heat-Induced Oxidative Stressed Broilers.

The gastrointestinal tract has a pivotal role in nutrient absorption, immune function, and overall homeostasis. The ileum segment of the small intestine plays respective roles in nutrient breakdown and absorption. The purpose of this study was to investigate the impact of heat-induced oxidative stress and the potential mitigating effects of an astaxanthin antioxidant treatment on the ileum of broilers. By comparing the growth performance and gene expression profiles among three groups-thermal neutral, heat stress, and heat stress with astaxanthin-thermal neutral temperature conditions of 21-22 °C and heat stress temperature of 32-35 °C, this research aims to elucidate the role of astaxanthin in supporting homeostasis and cellular protection in the ileum. Results showed both treatments under heat stress experienced reduced growth performance, while the group treated with astaxanthin showed a slightly lesser decline. Results further showed the astaxanthin treatment group significantly upregulated in the cytoprotective gene expression for HSF2, SOD2, GPX3, and TXN, as well as the upregulation of epithelial integrity genes LOX, CLDN1, and MUC2. In conclusion, our experimental findings demonstrate upregulation of cytoprotective and epithelial integrity genes, suggesting astaxanthin may effectively enhance the cellular response to heat stress to mitigate oxidative damage and contribute to cytoprotective capacity.

Transcriptomic and proteomic profiling of bi-partite and tri-partite murine iPSC-derived neurospheroids under steady-state and inflammatory condition.

induced-pluripotent stem cell (iPSC)-derived neurospheroid (NSPH) models are an emerging in vitro toolkit to study the influence of inflammatory triggers on neurodegeneration and repair in a 3D neural environment. In contrast to their human counterpart, the absence of murine iPSC-derived NSPHs for profound characterisation and validation studies is a major experimental research gap, even though they offer the only possibility to truly compare or validate in vitro NSPH responses with in vivo brain responses. To contribute to these developments, we here describe the generation and characterisation of 5-week-old CX3CR1eGFP+/- CCR2RFP+/- murine (m)iPSC-derived bi-partite (neurons + astrocytes) and tri-partite (neurons + astrocytes + microglia) NSPH models that can be subjected to cellular activation following pro-inflammatory stimulation. First, cytokine analysis demonstrates that both bi-partite and tri-partite NSPHs can be triggered to release IL6 and CXCL10 following three days of stimulation with, respectively, TNFα + IL1ß + IFNγ and LPS + IFNγ. Additionally, immunocytochemical analysis for G3BP1 and PABPC1 revealed the development of stress granules in both bi-partite and tri-partite NSPHs after 3 days of stimulation. To further investigate the observed signs of inflammatory response and cellular stress, we performed an untargeted transcriptomic and proteomic analysis of bi- and tri-partite NSPHs under steady-state and inflammatory conditions. Here, using the combined differential gene and protein expression profiles between unstimulated and stimulated NSPHs, Ingenuity Pathway Analysis (IPA) confirms the activation of canonical pathways associated with inflammation and cellular stress in both bi-partite and tri-partite NSPHs. Moreover, our multi-omics analysis suggests a higher level of downstream inflammatory responses, impairment of homeostatic and developmental processes, as well as activation of cell death processes in stimulated tri-partite NSPHs compared to bi-partite NSPHs. Concluding, these results emphasise the advantages of including microglia in NSPH research to study inflammation-induced neurodegeneration in a 3D neural environment.

Increased spontaneous activity and progressive suppression of adult neurogenesis in the hippocampus of rat offspring after maternal exposure to imidacloprid.

Imidacloprid (IMI) is a widely used neonicotinoid insecticide that poses risks for developmental neurotoxicity in mammals. The present study investigated the effects of maternal exposure to IMI on behaviors and adult neurogenesis in the hippocampal dentate gyrus (DG) of rat offspring. Dams were exposed to IMI via diet (83, 250, or 750 ppm in diet) from gestational day 6 until day 21 post-delivery on weaning, and offspring were maintained until adulthood on postnatal day 77. In the neurogenic niche, 750-ppm IMI decreased numbers of late-stage neural progenitor cells (NPCs) and post-mitotic immature granule cells by suppressing NPC proliferation and ERK1/2-FOS-mediated synaptic plasticity of granule cells on weaning. Suppressed reelin signaling might be responsible for the observed reductions of neurogenesis and synaptic plasticity. In adulthood, IMI at ≥ 250 ppm decreased neural stem cells by suppressing their proliferation and increasing apoptosis, and mature granule cells were reduced due to suppressed NPC differentiation. Behavioral tests revealed increased spontaneous activity in adulthood at 750 ppm. IMI decreased hippocampal acetylcholinesterase activity and Chrnb2 transcript levels in the DG on weaning and in adulthood. IMI increased numbers of astrocytes and M1-type microglia in the DG hilus, and upregulated neuroinflammation and oxidative stress-related genes on weaning. In adulthood, IMI increased malondialdehyde level and number of M1-type microglia, and downregulated neuroinflammation and oxidative stress-related genes. These results suggest that IMI persistently affected cholinergic signaling, induced neuroinflammation and oxidative stress during exposure, and increased sensitivity to oxidative stress after exposure in the hippocampus, causing hyperactivity and progressive suppression of neurogenesis in adulthood. The no-observed-adverse-effect level of IMI for offspring behaviors and hippocampal neurogenesis was determined to be 83 ppm (5.5-14.1 mg/kg body weight/day).

Indicators of technostress, their association with burnout and the moderating role of support offers among nurses in German hospitals: a cross-sectional study.

OBJECTIVES: To examine the level of indicators of technostress among nurses with and without a leadership position, the relationship between indicators of technostress and burnout and the moderating role of support offered by employers. The availability of support offers and further needs of nurses were also explored. DESIGN: Cross-sectional online survey. SETTING: Acute care hospitals in Germany. PARTICIPANTS: 303 nurses (73.3% female) who have worked at the hospital for at least 1 year and a minimum of 10 hours per week. PRIMARY AND SECONDARY OUTCOME MEASURES: Indicators of technostress (complexity, overload, usefulness, lack of technical support and unreliability) served as predictors in multiple linear regression analyses to examine their association with the primary outcome burnout. Support of employers was included as a moderator variable. Validated subscales from the Digital Stressors Scale and Copenhagen Burnout Inventory as well as open-ended questions were applied. RESULTS: There were no differences in the level of indicators of technostress found between nurses with and without a leadership position. Techno-overload (ß=0.259, p=0.004) and techno-complexity (ß=0.161, p=0.043) were significantly associated with burnout. Support by the employer moderated the relationship between lack of technical support and burnout significantly (R² change=0.026, F(1,292)=7.41, p=0.007). Support offers such as training, IT service and contact persons on the ward helped nurses to be more confident in the use of information and communication technologies. However, they expressed further needs with regard to these and new offers. CONCLUSIONS: There was an association between two indicators of technostress and burnout. Therefore, particular attention should be paid to supporting nurses in terms of techno-overload and techno-complexity. Furthermore, there is still a need for customised support and further offers from employers in the use of digital technologies.

Effects of a supraphysiological dose of testosterone cypionate on salivary gland function in adult male Wistar rats.

The abusive use of anabolic androgenic steroids has become a serious health problem worldwide, but its effects on oral health are still poorly understood. Therefore, the objective of this study was to evaluate the effects of a supraphysiological dose of testosterone cypionate (TC) on salivary biochemical, histomorphology, immunohistochemistry, and redox state parameters of parotid and submandibular glands. Twenty male Wistar rats, 12 weeks old, were divided into two groups (n=10/group): a control group and TC group, which received a dose of 20 mg/kg, once a week, for 6 weeks. Post treatment, the saliva and glands were collected. A supraphysiological dose of TC increased plasma and salivary testosterone concentrations. Although TC did not alter salivary flow, pH, and buffering capacity, the treatment increased the salivary secretion of total protein and reduced amylase, calcium, phosphate, and potassium. TC reduced the connective tissue area in the parotid gland and acinar area of the submandibular gland, while increasing the granular convoluted tubule area in the submandibular gland. Proliferating cell nuclear antigen was higher in the acinar cells of the submandibular glands from the TC group. Moreover, TC increased concentrations of total oxidant capacity and damaged lipids in both salivary glands, while total antioxidant activity and uric acid were lower in the submandibular gland, and reduced glutathione was higher in both glands. Superoxide dismutase, catalase, and glutathione peroxidase activities were higher in the parotid gland, while only glutathione peroxidase activity was lower in the submandibular gland of the TC group. In conclusion, TC abuse may be a potential factor for dysfunction of the parotid and submandibular glands, becoming a risk factor for the oral and systemic health of users.