Long-term Continuous Exposure Research Articles

A Noninvasive Quantitative Method for Evaluating Intestinal Exposure to Microplastics Based on the Excretion and Metabolism Patterns of Microplastics and Their Additives.

Microplastics (MPs) pose potential health risks to the intestinal tract and gut microbiota, a topic that has garnered significant attention. However, the absence of quantitative assessment methods for human gut MP exposure impedes related health risk assessments. Here, we performed long-term continuous exposure experiments on mice using MPs that mimic actual human exposure characteristics. The daily excretion of fecal MPs and the concentrations of phthalates (PAEs) and their metabolites (mPAEs) in serum and urine were detected. The cumulative excretion rate of fecal MPs remains stable at about 93%. A significant linear correlation was observed between MP exposure and concentration of mPAEs in urine for both low MP (LMP; 150 μg of MPs/d) (R2 = 0.90) and high MP (HMP; 360 μg of MPs/d) groups (R2 = 0.97). Moreover, a strong correlation was found between daily PAEs exposure and total MP-associated PAEs exposure in both LMP (R2 = 0.77) and HMP (R2 = 0.88) groups. Based on these findings, we established a noninvasive model and evaluated multiple MP exposure parameters in the human gut across 6 continents, 30 countries, and 133 individuals. This study offers novel insights for the quantitative assessment of in vivo MP exposure and provides technical support for assessing the health risks of MPs.

Lipid profile of blood serum of chickens under conditions of long-term exposure to extremely low frequency variable pulsed electromagnetic field

It has been proven that electromagnetic fields (EMF) of various intensities have various effects on living organisms – from a therapeutic effect to the appearance of various functional disorders. The purpose of this study was to investigate the pattern of long-term continuous exposure of poultry with extremely low frequency variable pulsed electromagnetic field (ELF-PEMF) of weak intensity on indicators of lipid metabolism in chickens. 150–day-old Tetra X breed chickens were irradiated with ELF-PEMF at a frequency of 8 Hz for about 30 minutes for 174 days. The irradiation regime of experimental groups 1 and 2 was continuous, and in groups 3 and 4 it was alternated with weekly breaks. In 1 experimental group, poultry was fed according to the basic diet with a protein content increased by 10–15 %, and in 2 – with a protein content reduced by 10–15 %. In the control group of non-irradiated poultry, the protein content in the diet corresponded to generally accepted norms. The results of the experiment proved that the irradiation regimes of ELF-PEMF selected by us have an effect on lipid metabolism in the body of Tetra X breed chickens. On the 112th day of the experiment, regardless of the used regimes of irradiation of chickens with ELF-PEMF and the protein level in the diet, in the blood serum of the experimental groups, compared to the control, an increase in the level of free triacylglycerols by 1.56–2.76 times was found; cholesterol level – by 1.04–1.39 times; of high-density lipoproteins (HDL) – by 1.24–1.84 times and the reduction of atherogenic index – by 1.41–1.73 times, which is predicted to have a positive effect on their health and productive qualities. Meanwhile, during longer exposure of chickens to ELF-PEMF, the level of triacylglycerols in the blood serum of experimental groups of chickens did not differ significantly from the indicators of non-irradiated poultry (control group). In general, by selecting different modes of irradiation with ELF-PEMF with different supply of protein in the rations, it is possible to influence the indicators of lipid metabolism of Tetra X breed chickens.

Comparison of the real-world safety of two different long-acting methylphenidate formulations (Medikinet® MR and Concerta®) - a Danish nationwide register-based cohort study.

Medikinet® MR and Concerta® are long-acting methylphenidate formulations used for the treatment of pediatric and adult attention-deficit/hyperactivity disorder (ADHD). The two formulations have shown comparable safety profiles in two head-to-head randomized controlled trials. However, real-world studies comparing the safety profiles of these products are not available. This study aimed to compare the real-world safety of Medikinet® MR and Concerta® using register data. This population-based cohort study was conducted based on data from Danish registries. The study included patients with continuous long-term (i.e., ≥12 months) exposure to either Medikinet® MR or Concerta® between 1995 and 2018. Outcomes included several selected adverse events of interest. A sensitivity analysis was performed, excluding patients exposed to Concerta® generics. For each outcome, Fisher's exact test was performed to compare the number of cases between the two groups. Odds ratios (ORs) and 95% confidence intervals were estimated using logistic regression models with patients exposed to Concerta® as the reference group. The study population included 1249 patients exposed to Medikinet® MR and 2455 patients exposed to Concerta®. No cases of cerebral arteritis or priapism were identified in either cohort. ORs for sudden death and anorexia could not be calculated due to the absence of cases in the Medikinet® MR cohort. For the remaining outcomes, no statistically significant difference in risk was found between Medikinet® MR-exposed and Concerta®-exposed patients. The sensitivity analysis produced results consistent with those obtained in the main analysis. The results of this population-based cohort study indicate that Medikinet® MR and Concerta® have comparable real-world safety profiles.

Ethylene inhibits photosynthesis via temporally distinct responses in tomato plants.

Ethylene is a volatile plant hormone that regulates many developmental processes and responses toward (a)biotic stress. Studies have shown that high levels of ethylene repress vegetative growth in many important crops, including tomato (Solanum lycopersicum), possibly by inhibiting photosynthesis. We investigated the temporal effects of ethylene on young tomato plants using an automated ethylene gassing system to monitor the physiological, biochemical, and molecular responses through time course RNA-seq of a photosynthetically active source leaf. We found that ethylene evokes a dose-dependent inhibition of photosynthesis, which can be characterized by 3 temporally distinct phases. The earliest ethylene responses that marked the first phase and occurred a few hours after the start of the treatment were leaf epinasty and a decline in stomatal conductance, which led to lower light perception and CO2 uptake, respectively, resulting in a rapid decline of soluble sugar levels (glucose, fructose). The second phase of the ethylene effect was marked by low carbohydrate availability, which modulated plant energy metabolism to adapt by using alternative substrates (lipids and proteins) to fuel the TCA cycle. Long-term continuous exposure to ethylene led to the third phase, characterized by starch and chlorophyll breakdown, which further inhibited photosynthesis, leading to premature leaf senescence. To reveal early (3 h) ethylene-dependent regulators of photosynthesis, we performed a ChIP-seq experiment using anti-ETHYLENE INSENSITIVE 3-like 1 (EIL1) antibodies and found several candidate transcriptional regulators. Collectively, our study revealed a temporal sequence of events that led to the inhibition of photosynthesis by ethylene and identified potential transcriptional regulators responsible for this regulation.

Residue dynamics of a contact and a systemic fungicide in pollen, nectar, and other plant matrices of courgette (Cucurbita pepo L.)

Pollen and nectar can be contaminated with a range of pesticides, including insecticides, fungicides, and herbicides. Since these matrices are important food sources for pollinators and other beneficial insects, their contamination can represent a key route of exposure. However, limited knowledge exists with respect to pesticide residue levels and their dynamics in these matrices for many crops and active ingredients (AIs). We used controlled glasshouse studies to investigate the residue dynamics of a systemic (cyprodinil) and a contact (fludioxonil) fungicide in the floral matrices and other plant parts of courgette/zucchini (Cucurbita pepo L.). We aimed to better understand the processes behind residue accumulation and decline in pollen and nectar. Each AI was applied to plants, either by spraying whole plants or by targeted spraying onto leaves only. Samples of pollen, nectar, anthers, flowers, and leaves were taken on the day of application and each subsequent morning for up to 13 days and analysed for residues using LC-MS/MS. Significant differences in residue levels and dynamics were found between AIs and floral matrices. The present study allowed for the identification of potential routes by which residues translocate between tissues and to link those to the physicochemical properties of each AI, which may facilitate the prediction of residue levels in pollen and nectar. Residues of the contact AI declined more quickly than those of the systemic AI in pollen and nectar. Our results further suggest that the risk of oral exposure for pollinators may be considerably reduced by using contact AIs during the green bud stage of plants, but application of systemic compounds could still result in a low, but continuous long-term exposure for pollinators with limited decline.

#4476 PRIMARY GLOMERULAR DISEASES AND LONG-TERM RISKS OF CKD PROGRESSION, CARDIOVASCULAR EVENTS AND DEATH: A SWEDISH NATIONWIDE COHORT STUDY

Abstract Background and Aims Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide (after diabetes and hypertension), little is known about their long-term risks and complications. Method Using data from the Swedish Renal Registry (SRR-CKD) 2005-2021, we compared clinical outcomes between patients with the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD] and membranous nephropathy [MN]) and patients with CKD attributed to non-inflammatory etiologies (i.e. without systemic auto-immune, inflammatory, infectious, hematologic malignancy, genetic disease, or polycystic kidney disease). Poisson models were used to estimate adjusted incidence rate ratios (IRR) of all-cause and cause-specific hospitalizations (cardiovascular-, acute kidney injury-, thromboembolism- and infection-related). Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) of kidney replacement therapy (KRT), major adverse cardiovascular events (MACE) and death. Results We identified 2967 patients with primary glomerular disease (71% men, age 57 years, eGFR 28 mL/min/1.73 m2, uACR 63 mg/mmol) and 40026 patients with a non-inflammatory CKD (64% men, age 74 years, eGFR 22 mL/min/1.73 m2, uACR 20 mg/mmol). As compared to non-inflammatory CKD, patients with primary glomerular diseases were younger, had a lower prevalence of cardiovascular disease, higher eGFR but higher albuminuria. Over median follow-up of 6.3 [3.3;9.9] years, there were median 3.0 [1.0;7.0] hospitalizations per patient, 9890 (23%) KRT, 11708 (27%) MACE, and 21091 (49%) deaths. As compared to non-inflammatory CKD, patients with primary glomerular disease had a lower risk of all-cause (IRR 0.77 [0.75;0.79]), and all cause-specific hospitalizations, MACE (HR 0.56 [0.50;0.63]) and death (HR 0.57 [0.52;0.62], but a similar risk of KRT (HR 1.02 [0.95;1.10]) or AKI (HR 0.84 [0.70;1.02]) (Figure 1). Within primary glomerular diseases and as compared to IgAN, patients with FSGS had a higher risk of death (HR 1.29 [1.03;1.60]) and MACE (HR 1.49 [1.12;1.97]), and patients with MN and MCD had a lower risk of KRT. Conclusion In this nationwide analysis of patients with advanced CKD undergoing nephrologist-care, those with primary glomerular disease have an observed lower risk of adverse clinical events compared to non-inflammatory CKD diseases. However, their risks of AKI or KRT are similar, emphasizing the need of adequate treatment strategies in this population. We speculate that the long-term continuous exposure to comorbidities like diabetes and hypertension in patients with non-inflammatory CKD might explain these differences. Within single primary glomerular disease etiologies, FSGS is associated with the highest risk of cardiovascular and fatal complications. The study received grant support from CSL Vifor.

Novel Perspectives on the Design and Development of a Long-Acting Subcutaneous Raltegravir Injection for Treatment of HIV-In Vitro and In Vivo Evaluation.

Antiretrovirals (ARVs) are a highly effective therapy for treatment and prevention of HIV infection, when administered as prescribed. However, adherence to lifelong ARV regimens poses a considerable challenge and places HIV patients at risk. Long-acting ARV injections may improve patient adherence as well as maintaining long-term continuous drug exposure, resulting in improved pharmacodynamics. In the present work, we explored the aminoalkoxycarbonyloxymethyl (amino-AOCOM) ether prodrug concept as a potential approach to long-acting ARV injections. As a proof of concept, we synthesised model compounds containing the 4-carboxy-2-methyl Tokyo Green (CTG) fluorophore and assessed their stability under pH and temperature conditions that mimic those found in the subcutaneous (SC) tissue. Among them, probe 21 displayed very slow fluorophore release under SC-like conditions (98% of the fluorophore released over 15 d). Compound 25, a prodrug of the ARV agent raltegravir (RAL), was subsequently prepared and evaluated using the same conditions. This compound showed an excellent in vitro release profile, with a half-life (t½) of 19.3 d and 82% of RAL released over 45 d. In mice, 25 extended the half-life of unmodified RAL by 4.2-fold (t½ = 3.18 h), providing initial proof of concept of the ability of amino-AOCOM prodrugs to extend drug lifetimes in vivo. Although this effect was not as pronounced as seen in vitro-presumably due to enzymatic degradation and rapid clearance of the prodrug in vivo-the present results nevertheless pave the way for development of more metabolically stable prodrugs, to facilitate long-acting delivery of ARVs.

In Vitro Cell Transformation Assays: A Valuable Approach for Carcinogenic Potentiality Assessment of Nanomaterials.

This review explores the application of in vitro cell transformation assays (CTAs) as a screening platform to assess the carcinogenic potential of nanomaterials (NMs) resulting from continuously growing industrial production and use. The widespread application of NMs in various fields has raised concerns about their potential adverse effects, necessitating safety evaluations, particularly in long-term continuous exposure scenarios. CTAs present a realistic screening platform for known and emerging NMs by examining their resemblance to the hallmark of malignancy, including high proliferation rates, loss of contact inhibition, the gain of anchorage-independent growth, cellular invasion, dysregulation of the cell cycle, apoptosis resistance, and ability to form tumors in experimental animals. Through the deliberate transformation of cells via chronic NM exposure, researchers can investigate the tumorigenic properties of NMs and the underlying mechanisms of cancer development. This article examines NM-induced cell transformation studies, focusing on identifying existing knowledge gaps. Specifically, it explores the physicochemical properties of NMs, experimental models, assays, dose and time requirements for cell transformation, and the underlying mechanisms of malignancy. Our review aims to advance understanding in this field and identify areas for further investigation.

Колебательный характер окислительных процессов в крови крыс при хроническом многочастотном электромагнитном облучении от систем сотовой связи стандартов GSM, UMTS и LTE

The paper presents results of research on effects of long term continuous animals exposure to multi-frequency electromagnetic fields of the mobile communication standards (GSM, UMTS and LTE). Prooxidant and antioxidant activity was investigated in the blood of exposed Wistar rats. The animals were continuously exposed to electromagnetic fields at frequencies of 1800, 2100 and 2600 MHz with the total power density of 250 muW/cm2 (GSM-20%; UMTS-20%; LTE-60%). Peripheral blood samples were taken from the affected and control rats after the decapitation at the end of each month of exposure. Fluctuations in indices of lipid peroxidation (diene conjugates) and antioxidant activity (enzyme, catalases) were observed at all stages of the exposure. The modulation effect of prooxidant and antioxidant activity in animals blood serum is suggested to depend on the amount of formed reactive oxygen species, and it may be caused by the direct effect of electromagnetic fields. The modulation effect of long-term continuous exposure to multi-frequency electromagnetic fields of mobile communication base stations on the blood lipid peroxidation may cause unfavorable consequences, which requires further study. The obtained results indicate necessity to take into account the detected modulating effect that can affect the level of reactive oxygen species.

Life on Magnet: Long-Term Exposure of Moderate Static Magnetic Fields on the Lifespan and Healthspan of Mice.

All living organisms on the Earth live and evolve in the presence of the weak geomagnetic field, a quasi-uniform static magnetic field (SMF). In the meantime, although the effects of moderate and high SMFs have been investigated on multiple aspects of a living organism, a long-term SMF exposure of more than 1 year has never been reported. Here, we investigated the influence of a moderate SMF (70-220 mT head-to-toe) long-term continuous exposure (1.7 years) to two different SMF directions on healthy male C57BL/6 mice. We found that not only was the lifespan of the mice prolonged, but their healthspan was also improved. The elevated plus maze test and open field test show that SMFs could significantly improve the exploratory and locomotive activities of the aged mice. The Morris water maze test shows that SMFs could improve their spatial learning ability and spatial memory. Tissue examinations reveal that SMFs have an ameliorative effect on oxidative stress in the brain of aged mice, which was reinforced by the cellular assays, showing that SMFs could protect the PC12 cells from D-gal-induced senescence by increasing superoxide dismutase, catalase, and reducing the malonaldehyde levels. Therefore, our data show that the 1.7-year SMF exposure can improve both the lifespan and healthspan of naturally aged mice due to reduced oxidative stress, which indicates that SMFs have the potential to be used as an adjuvant physical therapy to reduce the ageing-induced health risks to benefit animals, and even humans.

Physiological Response, Oxidative Stress Assessment and Aquaporin Genes Expression of Cherry Tomato (Solanum lycopersicum L.) Exposed to Hyper-Harmonized Fullerene Water Complex.

The rapid production and numerous applications of nanomaterials warrant the necessity and importance of examining nanoparticles in terms to their environmental and biological effects and implications. In this study, the effects of a water-soluble hyper-harmonized hydroxyl-modified fullerene (3HFWC) on cherry tomato seed germination, seedlings growth, physiological response and fruiting was evaluated. Changes in the photosynthetic pigments content, oxidative stress assessment, and aquaporin genes expression in cherry tomato plants were studied after during short- and long-term continuous exposure to 3HFWC nanosubstance (200 mg/L). Increased levels of photosynthetic pigments in leaves, lycopene in fruits, decreased levels of hydrogen peroxide content, activation of cellular antioxidant enzymes such as superoxide dismutase, catalase and peroxidase and increased aquaporin gene expression (PIP1;3, PIP1;5 and PIP2;4) were observed in 3HFWC nanosubstance-exposed plants in comparison to control, untreated cherry tomato plants. The 3HFWC nanosubstance showed positive effects on cherry tomato seed germination, plantlet growth and lycopene content in fruits and may be considered as a promising nanofertilizer.

Au Wire Ball Welding and Its Reliability Test for High-Temperature Environment.

The long-term application of sensors in a high-temperature environment needs to address several challenges, such as stability at high temperatures for a long time, better wiring interconnection of sensors, and reliable and steady connection of the sensor and its external equipment. In order to systematically investigate the reliability of thin coatings at high temperatures for a long time, Au and Cr layers were deposited on silicon substrates by magnetron sputtering. Additionally, samples with different electrode thicknesses were annealed at different temperatures for a varied duration to study the effect of electrode thickness, temperature, and duration on the reliability of samples. The results of tensile and probe tests before and after heat treatment revealed that the mechanical strength and electrical properties have changed after annealing. In addition, the bonding interface was analyzed by a cross-sectional electron microscope. The analysis showed that long-term continuous high-temperature exposure would result in thinning of the electrode, formation of pores, recrystallization, and grain growth, all of which can affect the mechanical strength and electrical properties. In addition, it was observed that increasing the thickness of the gold layer will improve reliability, and the test results show that although the thin metal layer sample is in poor condition, it is still usable. The present study provides theoretical support for the application of thin coatings in high temperatures and harsh environments.

Fibroblasts: Immunomodulatory factors in refractory diabetic wound healing.

Diabetes is a systemic disease in which patients with diabetes may develop peripheral neuropathy of the lower extremities and peripheral vascular disease due to long-term continuous exposure to high glucose. Delayed wound healing in diabetes is one of the major complications of diabetes. Slow wound healing in diabetic patients is associated with high glucose toxicity. When the condition deteriorates, the patient needs to be amputated, which seriously affects the quality of life and even endangers the life of the patient. In general, the delayed healing of diabetes wound is due to the lack of chemokines, abnormal inflammatory response, lack of angiogenesis and epithelial formation, and fibroblast dysfunction. The incidence of several chronic debilitating conditions is increasing in patients with diabetes, such as chronic renal insufficiency, heart failure, and hepatic insufficiency. Fibrosis is an inappropriate deposition of extracellular matrix (ECM) proteins. It is common in diabetic patients causing organ dysfunction. The fibrotic mechanism of diabetic fibroblasts may involve direct activation of permanent fibroblasts. It may also involve the degeneration of fibers after hyperglycemia stimulates immune cells, vascular cells, or organ-specific parenchymal cells. Numerous studies confirm that fibroblasts play an essential role in treating diabetes and its complications. The primary function of fibroblasts in wound healing is to construct and reshape the ECM. Nowadays, with the widespread use of single-cell RNA sequencing (scRNA-seq), an increasing number of studies have found that fibroblasts have become the critical immune sentinel cells, which can detect not only the activation and regulation of immune response but also the molecular pattern related to the injury. By exploring the heterogeneity and functional changes of fibroblasts in diabetes, the manuscript discusses that fibroblasts may be used as immunomodulatory factors in refractory diabetic wound healing, providing new ideas for the treatment of refractory diabetic wound healing.

Co-expression Mechanism Analysis of Different Tachyplesin I-Resistant Strains in Pseudomonas aeruginosa Based on Transcriptome Sequencing.

Tachyplesin I is a cationic antimicrobial peptide with 17 amino acids. The long-term continuous exposure to increased concentrations of tachyplesin I induced resistance in Pseudomonas aeruginosa. The global gene expression profiling of tachyplesin I–resistant P. aeruginosa strains PA-60 and PA-99 and the sensitive strain P. aeruginosa CGMCC1.2620 (PA1.2620) were conducted by transcriptome sequencing to analyze the common underlying mechanism of resistance to tachyplesin I in low- or high-resistance mutants. The co-expression patterns, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, sRNA target genes, and single-nucleotide polymorphism (SNP) change were analyzed for the co-expressed genes in this study. A total of 661 differentially co-expressed genes under treatments of PA1.2620 vs. PA-99 and PA1.2620 vs. PA-60 (HL) were divided into 12 kinds of expression patterns. GO and KEGG pathway enrichment analyses indicated that the enrichment of co-expressed genes was mainly associated with oxidoreductase activity, mismatched DNA binding, mismatch repair, RNA degradation of GO terms, aminoacyl-tRNA biosynthesis, and aminobenzoate degradation pathways, and so forth. The co-expressed resistance-related genes were mainly involved in antibiotic efflux and antibiotic inactivation. Seven co-expressed genes had SNP changes. Some co-expressed sRNAs were involved in P. aeruginosa resistance to tachyplesin I by regulating target genes and pathways related to resistance. The common resistance mechanism of P. aeruginosa among different mutants to tachyplesin I was mainly associated with the expression alteration of several genes and sRNA-regulated target genes related to resistance; few genes had base mutations. The findings of this study might provide guidance for understanding the resistance mechanism of P. aeruginosa to tachyplesin I.

Short-term intermittent cigarette smoke exposure enhances alveolar type 2 cell stemness via fatty acid oxidation

BackgroundCigarette smoke (CS) is associated with chronic obstructive pulmonary disease (COPD) and cancer. However, the underlying pathological mechanisms are not well understood. We recently reported that mice exposed to long-term intermittent CS for 3 months developed more severe emphysema and higher incidence of adenocarcinoma than mice exposed to long-term continuous CS for 3 months and long-term continuous CS exposure activated alveolar stem cell proliferation. However, the influence of variations in the CS exposure pattern in alveolar stem cell in unknown. Here, we exposed mice to 3 weeks of continuous or intermittent CS to identify whether different CS exposure patterns would result in differential effects on stem cells and the mechanisms underlying these potential differences.MethodsFemale mice expressing GFP in alveolar type 2 (AT2) cells, which are stem cells of the alveolar compartment, were exposed to mainstream CS via nasal inhalation. AT2 cells were collected based on their GFP expression by flow cytometry and co-cultured with fibroblasts in stem cell 3D organoid/colony-forming assays. We compared gene expression profiles of continuous and intermittent CS-exposed AT2 cells using microarray analysis and performed a functional assessment of a differentially expressed gene to confirm its involvement in the process using activator and inhibitor studies.ResultsAT2 cells sorted from intermittent CS-exposed mice formed significantly more colonies compared to those from continuous CS-exposed mice, and both CS-exposed groups formed significantly more colonies when compared to air-exposed cells. Comparative microarray analysis revealed the upregulation of genes related to fatty acid oxidation (FAO) pathways in AT2 cells from intermittent CS-exposed mice. Treatment of intermittent CS-exposed mice with etomoxir, an inhibitor of the FAO regulator Cpt1a, for 5 weeks resulted in a significant suppression of the efficiency of AT2 cell colony formation. In vitro treatment of naïve AT2 cells with a FAO activator and inhibitor further confirmed the relationship between FAO and AT2 stem cell function.ConclusionsAlveolar stem cell function was more strongly activated by intermittent CS exposure than by continuous CS exposure. We provide evidence that AT2 stem cells respond to intermittent CS exposure by activating stem cell proliferation via the activation of FAO.

Effects of Long-Term Exposure to L-Band High-Power Microwave on the Brain Function of Male Mice.

Currently, the impact of electromagnetic field (EMF) exposure on the nervous system is an increasingly arousing public concern. The present study was designed to explore the effects of continuous long-term exposure to L-band high-power microwave (L-HPM) on brain function and related mechanisms. Forty-eight male Institute of Cancer Research (ICR) mice were exposed to L-HPM at various power densities (0.5, 1.0, and 1.5 W/m2) and the brain function was examined at different time periods after exposure. The morphology of the brain was examined by hematoxylin-eosin (HE) and deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, cholinergic markers, oxidative stress markers, and the expression of c-fos were evaluated to identify a “potential” mechanism. The results showed that exposure to L-HPM at 1.5 W/m2 can cause generalized injuries in the hippocampus (CA1 and CA3) and cerebral cortex (the first somatosensory cortex) of mice, including cell apoptosis, cholinergic dysfunction, and oxidative damage. Moreover, the deleterious effects were closely related to the power density and exposure time, indicating that long-term and high-power density exposure may be detrimental to the nervous system.

Continuous Long-Term Exposure to Low Concentrations of MWCNTs Induces an Epithelial-Mesenchymal Transition in BEAS-2B Cells.

In the field of nanotechnology, the use of multi-walled carbon nanotubes (MWCNTs) is growing. Pulmonary exposure during their production, use, and handling is raising concerns about their potential adverse health effects. The purpose of this study is to assess how the physical characteristics of MWCNTs, such as diameter and/or length, can play a role in cellular toxicity. Our experimental design is based on the treatment of human bronchial epithelial cells (BEAS-2B) for six weeks with low concentrations (0.125–1 µg/cm2) of MWCNTs having opposite characteristics: NM-403 and Mitsui-7. Following treatment with both MWCNTs, we observed an increase in mitotic abnormalities and micronucleus-positive cells. The cytotoxic effect was delayed in cells treated with NM-403 compared to Mitsui-7. After 4–6 weeks of treatment, a clear cellular morphological change from epithelial to fibroblast-like phenotype was noted, together with a change in the cell population composition. BEAS-2B cells underwent a conversion from the epithelial to mesenchymal state as we observed a decrease in the epithelial marker E-cadherin and an increased expression of mesenchymal markers N-cadherin, Vimentin, and Fibronectin. After four weeks of recovery, we showed that the induced epithelial-mesenchymal transition is reversible, and that the degree of reversibility depends on the MWCNT.

Effect of Long-Term Continuous Light Exposure and Western Diet on Adropin Expression, Lipid Metabolism, and Energy Homeostasis in Rats.

Long-term continuous light exposure (CL) and western diet (WD) effects on Adropin expression, RORα, and Rev-erb-α nuclear receptors and energy homeostasis were studied in rats. Thirty-two male Wistar rats (250-290 g) were enrolled for 3 months in the following groups (n = 8/group): (a) Normal control group (NC), (b) CL group, (c) WD group, and (d) CL + WD group. Then, indirect calorimetry and food intake (FI) were measured. Finally, Adropin, hormone-sensitive lipase (HSL), adipocyte triglyceride lipase (ATGL), and free fatty acids (FFA) were measured. Additionally, the histopathology and gene expression of Enho, RORα, and Rev-erb-α genes were done. The CL alone elevated the Adropin plasma level and gene expression, increased RORα expression, and decreased the Rev-erb-α nuclear receptor expression mainly in the liver and kidney. Besides, CL increased the total energy expenditure (TEE) and decreased the respiratory quotient. WD alone or in combination with the CL reversed gene expression of Enho, RORα, and Rev-erb-α. Combined CL and WD increased the TEE, reduced the food intake, increased the ATGL, and reduced the Adropin level in addition to widespread degenerative changes in the liver, spleen, and renal tissues. The deleterious effects of CL and WD on energy homeostasis may include Adropin with the involvement of the RORα and Rev-erb-α nuclear receptors.

The Effect of Stress Using Long-Term Continuous LightExposure on Liver Cells in Male and Female Wistar Rats

AbstractBackground: Many modern lifestyles are unhealthy andcan negatively affect our health. Many studies showed thatthe stress caused pronounced action on the structure of variousbody systems. The liver is one of the body organs that can beheavily affected by stress. The liver can withstand stress forlonger periods and shows signs of damage very late althoughthe structural changes can be detected very early.Aim of Study: Is to examine the acute and chronic effect of acute and chronic stress of long-term continuous light exposure on the structure of the liver tissues.Material and Methods: 48 male and female Wistar rats (250-300g) were enrolled in 6 groups (n=8/group). Group (a);Normal male control group with normal light/dark exposure.Group (b); Normal female control group with normal light/darkexposure. Group (c); Continuous room light for 3 weeks malegroup as an acute stress model in which normally fed malerats exposed to continuous room light exposure for 3 weeks.Group (d); Continuous room light for 3 weeks female groupas an acute stress model in which normally fed female ratsexposed to continuous room light exposure for 3 weeks.Group (e); Continuous room light for 3 months male groupas a chronic stress model in which normally fed male ratsexposed to continuous light exposure for 3 months. Group (f); Continuous room light for 3 months female group as achronic stress model in which normally fed female rats exposed to continuous light exposure for 3 months.Results: Sections of liver tissues of the groups who livedunder acute stress showed generally, preserved hepatic archi-tecture. The hepatocytes showed marked ballooning (vacuolardegeneration). The sinusoids and central veins showed con-gestion. Sections of liver tissues of the groups who livedunder chronic stress conditions showed in general, preservedhepatic architecture. The hepatocytes showed ballooning (vacuolar degeneration), focal spotty necrosis, together withsome binucleated cells. The sinusoids & central vein showedcongestion.Conclusion: This study used 48 Wistar mice as a modelto assess the effect of stress on liver tissues. Continuous roomlight exposure was used as acute stress for 3 weeks and aschronic stress for 3 months. This stressful stimulus and its deleterious effect on the liver may be supported by the theoryof sympathetic nervous system overactivity. The examinedliver tissues in this study showed congestive and degenerativechanges both in acute and chronic stressed animals. Changingmodern lifestyles to one that respects the natural chronobiologyis important for our wellbeing.

Enhancement in the ATP level and antioxidant capacity of Caenorhabditis elegans under continuous exposure to extremely low-frequency electromagnetic field for multiple generations

Purpose Safety concerns about the effects of long-term extremely low-frequency electromagnetic field (ELF-EMF) exposure on human health have been raised. To explore the effects of continuous exposure to ELF-EMF on organisms for multiple generations, we selected Caenorhabditis elegans as a model organism and conducted long-term continuous exposure studies for multiple generations under 20 °C, 50 Hz, and 3 mT ELF-EMF. Materials and methods Each generation of worms was treated with ELF-EMF from the egg in the same environment. After long-term exposure to ELF-EMF, the body length of the worms was detected, and 15th generation adult worms were selected as the research object. The ATP level and ATPase were detected, and the expression levels of genes encoding ATP synthase (r53.4, hpo-18, atp-5, unc-32, atp-3) were detected by RT-PCR. In worm’s antioxidant system, the level of reactive oxygen species (ROS) was detected by dichlorofluorescein staining, and the total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT) activity were investigated. The expression of genes encoding superoxide dismutase (sod-1, sod-2, sod-3) was detected in adult (60 h) worms of the fifteenth generation (F15). Results These results showed that the body length of F15 worms increased significantly, ATP content increased significantly, ATP synthase activity was significantly enhanced, and the expression levels of the r53.4, hpo-18, atp-5, and atp-3 genes encoding ATPase were significantly upregulated in F15 worms. In addition, SOD activity increased significantly, and the expression levels of the sod-1, sod-2, and sod-3 genes encoding SOD were also significantly upregulated in F15 worms. Conclusions These results indicated that continuous exposure to 50 Hz, 3 mT ELF-EMF for multiple generations can increase the body length of worms, induce the synthesis of ATP and enhance the antioxidant capacity of worms.