Effects Of Long-term Exposure Research Articles

Long-Term Neurotoxic Effects and Alzheimer's Disease Risk of Early EHDPP Exposure in Zebrafish: Insights from Molecular Mechanisms to Adult Pathology.

2-Ethylhexyl diphenyl phosphate (EHDPP), ubiquitously monitored in environmental media, is highly bioaccumulative and may pose long-term risks, even after short-term exposure. In this investigation, larval zebrafish were exposed to 0.05, 0.5, and 5.0 μg/L EHDPP from 4 to 120 h postfertilization (hpf) to examine the long-term neurotoxicity effects of early exposure. Exposure to 5.0 μg/L EHDPP yielded hyperactive locomotor behavior, which was characterized by increased swimming speed, larger turning angles, and heightened sensitivity to light-dark stimulation. The predicted targets of EHDPP (top 100 potential macromolecules) were primarily associated with brain diseases like Alzheimer's disease (AD). Comparisons of differentially expressed genes (DEGs) from AD patients (GSE48350) and RNA-seq data from EHDPP-exposed zebrafish confirmed consistently abnormal regulatory pathways. EHDPP's interaction with M1 and M5 muscarinic acetylcholine receptors likely disrupted calcium homeostasis, leading to mitochondrial dysfunction and neurotransmitter imbalance as well as abnormal locomotor behavior. Especially, 5.0 μg/L EHDPP exposure during early development (4-120 hpf) triggered early- and midstage AD-like symptoms in adulthood (180 dpf), characterized by cognitive confusion, aggression, blood-brain barrier disruption, and mitochondrial damage in brains. These findings provide deep insights into the long-term neurotoxicity effects and Alzheimer's disease risks of early EHDPP exposure at extremely low dosages.

Risk of death from hematological malignancies in the South Urals Population Exposed to Radiation cohort

The results of studies of long-term effects of population exposure in the South Urals in the 1950s were based for a long time on studies of the effects of exposure in the Techa River cohort and later in the East Urals Radioactive Trace cohort. After the creation of the South Urals Population Exposed to Radiation cohort, combining all persons exposed in the South Urals in the period from January 1, 1950, to December 31, 1960 the size of the cohort doubled, follow-up period reached 71 years, and the number of person-years at risk increased to 1,964,333. The average dose to red bone marrow for all cohort members was 231mGy. Regression analysis using a simple parametric excess relative risk model was performed using the EPICURE statistical package. The analysis resulted in confirmation of a statistically significant (p <0.001) linear doseresponse relationship of mortality for all hemoblastoses, and leukemia. The excess relative risk and 95% confidence intervals of death at 2-year latency period from all hemoblastoses were 0.71/Gy (0.28;1.31); from all leukemias - 1.28/Gy (0.55-2.39) and from leukemias excluding chronic lymphocytic leukemia -1.52/Gy (0.64-2.94). The quadratic model also significantly described the dose dependence; (the differences between the models were not significant). Increasing the follow-up period to 71 years resulted in a slight decrease in risk estimates. The width of the confidence intervals of the risk estimates decreased by more than a factor of 3 compared to earlier studies in the Techa River cohort, which indicates a decrease in uncertainties of risk estimates. Increasing the size of the cohort made it possible to obtain significant risk values for individual population groups (by sex, age, etc.). Analysis of risk values modification did not reveal significant differences in dose dependence on the studied factors, including attained age and age at exposure. The study will be continued to investigate in more detail the influence of time-dependent factors on dose dependence, as well as to assess the risk of death from different cellular forms of leukemia.

Plastic debris exposure and effects in rivers: Boundaries for efficient ecological risk assessment.

Until recently, plastic pollution research was focused on the marine environments, and attention was given to terrestrial and freshwater environments latter. This discussion paper aims to put forward crucial questions on issues that limit our ability to conduct reliable plastic ecological risk assessments in rivers. Previous studies highlighted the widespread presence of plastics in rivers, but the sources and levels of exposure remained matters of debate. Field measurements have been carried out on the concentration and composition of plastics in rivers, but greater homogeneity in the choice of plastic sizes, particularly for microplastics by following the recent ISO international standard nomenclature, is needed for better comparison between studies. The development of additional relevant sampling strategies that are suited to the specific characteristics of riverine environments is also needed. Similarly, we encourage the systematic real-time monitoring of environmental conditions (e.g., topology of the sampling section of the river, hydrology, volumetric flux and velocity, suspended matters concentration) to better understand the origin of variability in plastic concentrations in rivers. Furthermore, ingestion of microplastics by freshwater organisms has been demonstrated under laboratory conditions, but the long-term effects of continuous microplastic exposure in organisms are less well understood. This discussion paper encourages an integrative view of the issues involved in assessing plastic exposure and its effects on biota, in order to improve our ability to carry out relevant ecological risk assessments in river environments.

Lysosomal disruption, mitochondrial impairment, histopathological and oxidative stress in rat's nervous system after exposure to a neonicotinoid (imidacloprid).

Imidacloprid (IMI), a neonicotinoid pesticide, has been widely used due to its high efficiency against insect pests. However, its prolonged exposure may pose significant risks to non-target organisms, including mammals. Recent studies have raised concerns about its potential neurotoxicity, yet the underlying mechanisms remain poorly understood. This study aimed to assess the neurotoxic effects of chronic Imidacloprid exposure in Wistar rats, focusing on oxidative stress, mitochondrial dysfunction, and lysosomal disruption. Wistar rats were orally administered two doses of Imidacloprid (5mg/kg and 50mg/kg body weight) for three months. Neurotoxic effects were assessed by measuring key biochemical markers such as the enzymatic activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione S-transferase (GST). Non-enzymatic markers, including glutathione (GSH) levels and malondialdehyde (MDA) index, were also evaluated. Mitochondrial function was assessed by analyzing oxygen consumption, swelling, and membrane permeability and histopathological changes. Lysosomal stability was examined using the Neutral Red Retention Time (NRRT) assay. Neutral red is a dye that accumulates in the acidic environment of lysosomes. Healthy lysosomes retain the dye, while compromised lysosomes lose it, indicating destabilization. By measuring the amount of neutral red retained in lysosomes, the NRRT assay assesses lysosomal integrity. Lysosomal pH variations were also monitored to evaluate functional changes. Microscopic analysis provided insight into structural changes in lysosomes and other cell components. Lysosomal destabilization was further confirmed by morphological alterations observed through light microscopy, revealing a progressive, time-dependent degeneration of lysosomal structures, including lysosomal expansion, neutral red dye leakage, and cell rounding. These changes reflected a temporal evolution of lysosomal damage, progressing from minor structural disruptions to more severe alterations as exposure continued, observable at the microscopic level. During the study, clinical observations of intoxicated rats included symptoms such as lethargy, reduced activity levels, and impaired motor coordination. High-dose Imidacloprid exposure led to noticeable behavioral changes, including decreased exploratory behavior and altered grooming patterns. Additionally, signs of neurotoxic effects, such as tremors or ataxia, were observed in the rats exposed to the higher dose, reflecting the systemic impact of chronic pesticide exposure. The results revealed a significant decrease in the enzymatic activities of CAT, GPx, and SOD, accompanied by an increase in GST activity. A notable reduction in glutathione levels and a rise in MDA index were observed, indicating enhanced oxidative stress in the brain. Mitochondrial impairment was evidenced by disturbances in oxygen consumption, increased swelling, and altered membrane permeability. Lysosomal destabilization was confirmed by reduced retention of neutral red dye, structural changes in lysosomes, and a significant rise in lysosomal pH in the IMI-exposed groups. In addition, the histopathological features indicate that imidacloprid at the given dose and exposure duration may have caused notable neurotoxic effects in Wistar rat brain tissue. Chronic exposure to Imidacloprid induces oxidative stress, mitochondrial dysfunction, lysosomal disruption and histopathological alterations in the central nervous system of Wistar rats. These findings provide valuable insights into the neurotoxic mechanisms of neonicotinoid pesticides, highlighting the need for further research to understand the long-term effects of Imidacloprid exposure on mammalian health.

Detrimental effect of prenatal progesterone exposure on anxiety and depressive-like responses in adult male and female rat offspring: role of plasma, hippocampal corticosterone and hippocampal progesterone receptors

In clinical practice, the use of exogenous progesterone (Pro) is often required in assisted reproduction programs due to reduced levels of the hormone and the risk of miscarriage. Exposure to the hormone reduces anxiety in rodents, but the long-term effects of prenatal exposure in adult offspring are unknown. Therefore, the present study was designed to investigate the effect of prenatal Pro treatment on anxiety- and depression-like behavior and the effect on plasma, hippocampal corticosterone (CORT) and hippocampal progesterone receptor (PR) in young adult male and female rat offspring. The behavioral responses of offspring of both sexes were tested in the open field, and the elevated plus maze tests, and for depressive-like behavior in the sucrose preference test, the forced swimming test and the splash test. CORT levels and PR expression were measured by ELISA. The results indicate that prenatal Pro exposure at low and high doses (10 and 50 mg/kg, s.c. during G0-G10) induces anxiogenic and depressive-like effects compared to vehicle-treated controls, which are associated with high plasma and hippocampal CORT levels and upregulated hippocampal PR in male and female adult offspring. Our results demonstrate that prenatal Pro exposure has detrimental effects on the emotional status of male and female adult offspring, which may be associated with long-term changes in hormonal homeostasis.

The Effect of Long-Term Particulate Matter Exposure on Respiratory Mortality: Cohort Study in China.

Particulate matter (PM), which affects respiratory health, has been well documented; however, substantial evidence from large cohorts is still limited, particularly in highly polluted countries and for PM1. Our objective was to examine the potential causal links between long-term exposure to PMs (PM2.5, PM10, and more importantly, PM1) and respiratory mortality. A total of 580,757 participants from the Guangzhou area, China, were recruited from 2009 to 2015 and followed up through 2020. The annual average concentrations of PMs at a 1-km spatial resolution around the residential addresses were estimated using validated spatiotemporal models. The marginal structural Cox model was used to estimate the associations of PM exposure with respiratory mortality, accounting for time-varying PM exposure. Results were stratified by demographics and lifestyle behaviors factors. Among the participants, the mean age was 48.33 (SD 17.55) years, and 275,676 (47.47%) of them were men. During the follow-up period, 7260 deaths occurred due to respiratory diseases. The annual average concentrations of PM1, PM2.5, and PM10 showed a declining trend during the follow-up period. After adjusting for confounders, a 6.6% (95% CI 5.6%-7.6%), 4.2% (95% CI 3.6%-4.7%), and 4.0% (95% CI 3.6%-4.5%) increase in the risk of respiratory mortality was observed following each 1-μg/m3 increase in concentrations of PM1, PM2.5, and PM10, respectively. In addition, older participants, nonsmokers, participants with higher exercise frequency, and those exposed to a lower normalized difference vegetation index tended to be more susceptible to the effects of PMs. Furthermore, participants in the low-exposure group tended to be at a 7.6% and 2.7% greater risk of respiratory mortality following PM1 and PM10 exposure, respectively, compared to the entire cohort. This cohort study provides causal clues of the respiratory impact of long-term ambient PM exposure, indicating that PM reduction efforts may continuously benefit the population's respiratory health.

Interactive effects of long-term exposure to air pollutants on SARS-CoV-2 infection and severity: a northern Italian population-based cohort study.

We examined interactions, to our knowledge not yet explored, between long-term exposures to particulate matter (PM 10 ) with nitrogen dioxide (NO 2 ) and ozone (O 3 ) on SARS-CoV-2 infectivity and severity. We followed 709,864 adult residents of Varese Province from 1 February 2020 until the first positive test, COVID-19 hospitalization, or death, up to 31 December 2020. We estimated residential annual means of PM 10 , NO 2 and O 3 in 2019 from chemical-transport and random-forest models. We estimated interactive effects of pollutants with urbanicity on SARS-CoV-2 infectivity, hospitalization, and mortality endpoints using Cox regression models adjusted for socio-demographic factors and comorbidities, and additional cases due to interactions using Poisson models. 41,065 individuals were infected, 5,203 were hospitalized and 1,543 died from COVID-19 during follow-up. Mean PM 10 was 1.6 times higher and NO 2 2.6 times higher than WHO limits, with wide gradients between urban and non-urban areas. PM 10 and NO 2 were positively associated with SARS-CoV-2 infectivity and mortality, and PM 10 with hospitalizations in urban areas. Interaction analyses estimated that the effect of PM 10 (per 3.5 µg/m 3 ) on infectivity was strongest in urban areas (HR=1.12, 95%CI:1.09-1.16), corresponding to 854 additional cases per 100,000 person-years, and in areas at high NO 2 co-exposure (HR=1.15, 1.08-1.22). At higher levels of PM 10 co-exposure the protective association of ozone reversed (HR=1.32, 1.17-1.49), yielding to 278 additional cases per µg/m 3 increase in O 3 . We estimated similar interactive effects for severity endpoints. We estimate that interactive effects between pollutants exacerbated the burden of SARS-CoV-2 pandemic in urban areas.

Long-term exposure to wildland fire smoke PM2.5 and mortality in the contiguous United States

Despite the substantial evidence on the health effects of short-term exposure to ambient fine particles (PM2.5), including increasing studies focusing on those from wildland fire smoke, the impacts of long-term wildland fire smoke PM2.5 exposure remain unclear. We investigated the association between long-term exposure to wildland fire smoke PM2.5 and nonaccidental mortality and mortality from a wide range of specific causes in all 3,108 counties in the contiguous United States, 2007 to 2020. Controlling for nonsmoke PM2.5, air temperature, and unmeasured spatial and temporal confounders, we found a nonlinear association between 12-mo moving average concentration of smoke PM2.5 and monthly nonaccidental mortality rate. Relative to a month with the long-term smoke PM2.5 exposure below 0.1 μg/m3, nonaccidental mortality increased by 0.16 to 0.63 and 2.11 deaths per 100,000 people per month when the 12-mo moving average of PM2.5 concentration was of 0.1 to 5 and 5+ μg/m3, respectively. Cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, and chronic kidney disease mortality were all found to be associated with long-term wildland fire smoke PM2.5 exposure. Smoke PM2.5 contributed to approximately 11,415 nonaccidental deaths/y (95% CI: 6,754, 16,075) in the contiguous United States. Higher smoke PM2.5-related increases in mortality rates were found for people aged 65 and above. Positive interaction effects with extreme heat were also observed. Our study identified the detrimental effects of long-term exposure to wildland fire smoke PM2.5 on a wide range of mortality outcomes, underscoring the need for public health actions and communications that span the health risks of both short- and long-term exposure.

Land use transformations in the Brazilian Savanna: A decade of soil erosion and runoff measurements

Changes in land cover and land use (LULC) are one of the main drivers of erosion and runoff. How ever, most research has relied on short-term observations and only focused on one or two land cover types. We investigated the long-term trade-off between common agricultural land covers (sugarcane, pasture, and soybean), runoff, and soil loss rates. We compared these to native forest (wooded Cerrado) and bare soil. The field observations were done in 100 m2 experimental plots in Brazil maintained during the past 10 years. The paper provides three main contributions: (1) long-term runoff and soil loss rates of plots under different LULCs, (2) comparison of runoff, soil loss, and pedological characteristics between plots constructed 10 years apart, and (3) analysis of the trade-off between different LULCs. When ranking land covers based on runoff and soil loss rates, there is a shift in ranking positions, making it difficult to determine which one is more environmentally harmful. However, it is evident that whatever agricultural practice is used, there is a significant impact when compared to native forest. For example, the area converted to pasture resulted in almost 20 times higher runoff, while conversion to sugarcane resulted in 5 times higher soil loss. Not only land cover plays a major influencing factor, but also weathering exposing time. Areas under the same land cover and environmental conditions had different rates of soil loss and runoff due to long-term exposure effects such as soil crusting. Our findings have high relevance for the hydrological and agricultural community by demonstrating (i) the magnitude of trade-off in terms of soil loss and runoff due to land cover changes and (ii) that soil loss should not be assumed to be a linear process over time, as it is commonly assumed.

Air pollutants and primary liver cancer mortality: a cohort study in crop-burning activities and forest fires area.

Northern Thailand experiences high levels of air pollution in the dry season due to agricultural waste burning and forest fires. Some air pollutants can enter the bloodstream, and the liver has the role of detoxifying these along with other harmful substances. In this study, we assessed the effects of long-term exposure to air pollutants on liver cancer mortality in this area. A cohort of 10,859 primary liver cancer patients diagnosed between 2003 and 2018 and followed up to the end of 2020 were included in the study. Extended time-varying covariates of the annually averaged pollutant concentrations updated each year were utilized. The associations between air pollutants and mortality risk were examined by using a Cox proportional hazard model. Metastatic cancer stage had the highest adjusted hazard ratio (aHR) of 3.57 (95% confidence interval (CI):3.23-3.95). Being male (aHR = 1.10; 95% CI: 1.04-1.15), over 60 years old (aHR = 1.16; 95% CI: 1.11-1.21), having a history of smoking (aHR = 1.16; 95%CI: 1.11-1.22), and being exposed to a time-updated local concentration of PM2.5 of 40 μg/m3 (aHR = 1.10; 95% CI: 1.05-1.15) increased the mortality risk. We found that air pollution is one of several detrimental factors on the mortality risk of liver cancer.

The effect of DMSO on Saccharomyces cerevisiae yeast with different energy metabolism and antioxidant status

We studied the effect of dimethyl sulfoxide (DMSO) on the biochemical and physiological parameters of S. cerevisiae yeast cells with varied energy metabolism and antioxidant status. The wild-type cells of varied genetic backgrounds and their isogenic mutants with impaired antioxidant defences (Δsod mutants) or response to environmental stress (ESR) (Δmsn2, Δmsn4 and double Δmsn2msn4 mutants) were used. Short-term exposure to DMSO even at a wide range of concentrations (2–20%) had little effect on the metabolic activity of the yeast cells and the stability of their cell membranes, but induced free radicals production and clearly altered their proliferative activity. Cells of the Δsod1 mutant showed greater sensitivity to DMSO in these conditions. DMSO at concentrations from 4 to 10–14% (depending on the strain and genetic background) activated the ESR programme. The effects of long-term exposure to DMSO were mainly depended on the type of energy metabolism and antioxidant system efficiency. Yeast cells with reduced antioxidant system efficiency and/or aerobic respiration were more susceptible to the toxic effects of DMSO than cells with a wild-type phenotype and respiro-fermentative or fully fermentative metabolism. These studies suggest a key role of stress response programs in both the processes of cell adaptation to small doses of this xenobiotic and the processes related to its toxicity resulting from large doses or chronic exposure to DMSO.

Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos

Objective: To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells. Methods: In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm(2) chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet-t test. Results: Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased (P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased (P<0.05) . Conclusion: Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

Monitoring of Non-Maximum-Residue-Level Pesticides in Animal Feed: A Study from 2019 to 2023.

Pesticides play a critical role in modern agriculture by protecting crops and ensuring higher yields, but their widespread use raises concerns about human health and environmental impact. Regulatory agencies impose Maximum Residue Levels (MRLs) to ensure safety, and the European Food Safety Authority (EFSA) assesses pesticide risks. This study monitored pesticide residues in 169 feed samples from Piedmont (Italy) collected between 2019 and 2023. Using GC-MS/MS, residues were found in 92% of animal-based and 70% of cereal-based feedstuffs. The most common pesticides in cereal-based feeds were pyrimiphos-methyl, deltamethrin, cypermethrin, azoxystrobin, and tetramethrin, and the pesticide synergist piperonyl-butoxide demonstrated a significant increase in contaminated samples in 2023. The lower concentrations in 2021 were likely due to COVID-19 impacts on pesticide availability. In animal-based feeds, common pesticides included deltamethrin, cypermethrin, and the pesticide synergist piperonyl-butoxide. The results highlight the pervasive presence of low-dose pesticide mixtures in feed and food chains, which could impact health, although do not pose acute risks. The study emphasizes the need for ongoing pesticide monitoring and awareness of the long-term effects of chronic pesticide exposure on animal, human, and environmental health.

The Potential Utility of Retinal Biomarkers to Index Central Nervous System Effects of Repetitive Blast Exposure in Military Personnel.

Military personnel exposed to blasts receive repeated subconcussive head impacts. Although these events typically do not cause immediate symptoms and do not lead to medical evaluation, the cumulative effects of subconcussive impacts can be significant and can include postconcussive symptoms, changes in brain structure and function, long-term cognitive dysfunction, depression, and chronic traumatic encephalopathy. Retinal measures such as thickness of retinal neural layers, density of retinal microvasculature, and strength of retinal neuronal firing are associated with cognitive function and brain structure and function in healthy populations and in neurodegenerative disease cohorts, and changes over time in retinal indices predict cognitive decline and brain atrophy in longitudinal studies in a range of medical populations. This commentary highlights the potential benefits of using retinal biomarkers in the routine screening and monitoring of brain health in warfighters and veterans. Retinal measures can be rapidly acquired (often in a matter of seconds) using methods that are inexpensive and noninvasive, and they can be collected with movable and often portable equipment that uses automated scoring routines that can be used for prediction and decision-making at the individual level. To date, however, retinal biomarkers have not been included in studies of blast overpressure exposures in military personnel. Despite this, preclinical and human evidence suggests that they could be among the most effective methods for tracking central nervous system damage in people exposed to repeated blasts. Retinal biomarkers could also contribute to brief test batteries to determine who is most at risk for long-term negative effects of future exposures. In addition, the sensitivity of retinal indices to blast exposure and mild traumatic brain injury suggests that they should be incorporated into research on strategies to minimize or prevent blast-related short- and long-term central nervous system changes in blast-exposed military personnel.

Effects of Long-Term Exposure to Ambient Formaldehyde on Hypertension and Angina Pectoris Symptoms: Evidence From the WHO SAGE Cohort Study.

We aimed to investigate the associations of long-term exposure to ambient formaldehyde with hypertension and angina pectoris symptoms in Chinese adults. Participants' information was obtained from the WHO SAGE (World Health Organization Study on Global Aging and Adult Health) study. The Cox proportional hazards regression model was applied to estimate the associations of formaldehyde with hypertension and angina pectoris symptoms. Mediating effect analysis was used to investigate the mediating effect of hypertension between formaldehyde exposure and angina pectoris symptoms. Long-term exposure to formaldehyde was positively associated with the risk of angina pectoris symptoms (hazard ratio [HR], 1.66 [95% CI, 1.29-2.13], per interquartile range [IQR], 3.33, 1015 molecules/cm2) and hypertension (HR, 1.17 [95% CI, 1.02-1.34], per IQR, 3.34, 1015 molecules/cm2). The associations between formaldehyde and angina pectoris symptoms were greater in participants aged ≥65 years (HR, 1.90 [95% CI, 1.29-2.80]) and in rural areas (HR, 2.71 [95% CI, 1.54-4.77]), whereas the associations of formaldehyde with hypertension were stronger in men (HR, 1.27 [95% CI, 1.02-1.58]), rural areas (HR, 1.22 [95% CI, 0.94-1.59]), and in ever smokers (HR, 1.33 [95% CI, 1.02-1.72]). The mediation effect analysis indicated that 18.44% (95% CI, 2.17-37.65) of the association between formaldehyde exposure and angina pectoris symptoms was mediated by hypertension. Long-term exposure to ambient formaldehyde was positively associated with hypertension and angina pectoris symptoms. The effects of formaldehyde may be modified by age, sex, urbanicity, and smoking status. Hypertension might play a mediating effect in formaldehyde-induced angina pectoris symptoms.

Assessment of sub-lethal effects of Celcron on Java barb through erythrocyte morphology and acetylcholinesterase activity: Implications for environmental health in aquatic ecosystems

Industrialization and the extensive use of chemicals have raised significant concerns about their environmental impacts, particularly on aquatic ecosystems. This study evaluated the sub-lethal effects of Celcron (Cec), an organophosphate insecticide, on the Java barb (Barbonymus gonionotus) through erythrocyte morphology and acetylcholinesterase (AChE) activity, aiming to refine biomarkers for environmental health assessments. We hypothesized that sub-lethal Cec exposure would induce significant erythrocyte abnormalities and decrease AChE activity in Java barb, with variable recovery rates between gill and kidney tissues. To test this, we exposed the juvenile Java barbs to two sub-lethal Cec concentrations - 0.01 ppm (10 % of the LC50) and 0.05 ppm (50 % of the LC50) -for 60 days. After the exposure period, the fish were placed in pesticide-free water to allow for recovery. Results indicated a significant decline in AChE activity in both liver and kidney tissues, with activity levels showing gradual recovery over time. Erythrocyte abnormalities, including nuclear and cellular changes, were significantly elevated in response to Cec exposure. The frequency of nuclear abnormalities such as micronuclei and binucleation increased in a concentration- and duration-dependent manner, with the gill blood exhibiting higher sensitivity and slower recovery compared to kidney blood. Cellular abnormalities such as twin, teardrop and spindle-shaped cells were also more prevalent in Cec-treated fish. Recovery from these abnormalities was observed but varied between gill and kidney blood, with gill blood showing higher sensitivity and slower recovery compared to kidney blood. This study underscores the utility of AChE activity and erythrocyte abnormalities as biomarkers for assessing pesticide impacts on aquatic organisms. The findings highlight the sensitivity of fish erythrocytes to environmental contaminants and emphasize the need for continued research to better understand the long-term effects of pesticide exposure on aquatic health and ecosystem stability.

The effects of long-term radiation exposure on the reproductive structures of Glyceria maxima (Hartm.) Holmb.: A case study in the Chornobyl exclusion zone

During the acute phase of the Chornobyl accident the biota of the contaminated area was exposed to high doses of ionising radiation. Although these doses decreased significantly over the years, the exposure persisted over a prolonged period. This long-term exposure can be considered as a direct cause of genetic modifications occurring in organisms, and the search for correlative changes in the state of biota under the impact of radioactive contamination is an extremely urgent task. The aquatic macrophyte Glyceria maxima is the most common coenosis-forming plant of the littoral vegetation of the floodplain water bodies in the Chornobyl Exclusion Zone, and is capable of concentrating radionuclides in significant quantities. In this study, we aim to determine whether long-term radiation exposure has affected organs of reproductive structure (flower, pollen, seed) and, consequently, the viability of local populations of this species. All the traits analysed showed an inverse relationship with the absorbed dose rate of the maternal plants. It was determined that with an increase in the absorbed dose rate, the pollen size decreases, and the range of individual grains in the sample begins to vary more: small, heterogeneous in shape and size pollen grains are formed. Additionally, a decrease in pollen grain size correlates with a decrease in the proportion of fertile pollen. Pollen grains viability (fertility) decreases by 20–40% with increasing radiation dose rate. The response of reproductive structures to radiation exposure is non-linear: already at low doses (>2 μGy/h), negative changes in functional and morphological traits are observed, while at higher doses (9–13 μGy/h), the changes slow down. It is assumed that the radiation exposure mainly affects the early reproductive stages (pollen grains and partially flowers), while the main nutrients in water, that determine the trophic status of the reservoir, affects the late stages (seeds).

Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.

Introduction: Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats. Materials and Methods: Male and female neonatal Sprague Dawley rats were treated with CBD (50 mg/kg) intraperitoneally on postnatal day (PND) 1, 3, and 5 and evaluated for behavioral and neuronal morphological changes during early adulthood. Rats were subjected to a series of behavioral tasks to evaluate long-term effects of neonatal CBD exposure, including the Barnes maze, open field, and elevated plus maze paradigms to assess spatial memory and anxiety-like behavior. Following behavioral evaluation, animals were sacrificed, and neuronal morphology of the cortex and hippocampus was assessed using Golgi-Cox (GC) staining. Results: Rats treated with CBD displayed a sexually dimorphic response in spatial memory, with CBD-treated females developing a deficit but not males. CBD did not elicit alterations in anxiety-like behavior in either sex. Neonatal CBD caused an overall decrease in dendritic length and spine density (apical and basal) in cortical and hippocampal neurons in both sexes. Sholl analysis also revealed a decrease in dendritic intersections in the cortex and hippocampus, indicating reduced dendritic arborization. Conclusions: This study provides evidence that neonatal CBD exposure perturbs normal brain development and leads to lasting alterations in spatial memory and neuronal dendrite morphology in early adulthood, with sex-dependent sensitivity.

Integrated Biomarker Response Emphasizing Neuronal Oxidative Stress and Genotoxicity Induced by Oxamyl in Sprague Dawley Rats: Ameliorative Effect of Ginseng as a Neuroprotective Agent.

Climate change has led to increased and varying pest infestation patterns, triggering a rise in pesticide usage and exposure. The effects of oxamyl, a widely used nematicide in Egypt, encompasses typical signs of carbamate intoxication; nevertheless, long-term effects of oxamyl exposure, particularly on the nervous system, require further elucidation. This study systematically investigated the mechanism and manifestations of repeated subacute exposure to sublethal doses of oxamyl in male SD rats. Data showed a dose-dependent genotoxic effect, manifested as increased bone marrow micronuclei and decreased brain expression of key genes involved in neurogenesis and neuronal development. Coincidently, brain histopathology showed dose-dependent neurodegeneration in various regions, associated with a significant increase in GFAP immunoreactivity, indicative of neuroinflammation. Biochemical examination revealed a typical pattern of cholinesterase inhibition by carbamates in serum and brain tissue, as well as increased oxidative stress markers in the brain such as SOD activity reduction, alongside an increase in NO and MDA. The ability of Ginseng at a 100 mg/Kg dose to ameliorate the effects of oxamyl exposure was investigated. Ginseng use, either as a protective or therapeutic regimen, attenuated the observed genotoxic, neuroinflammatory, and biochemical alterations. Our results indicate that repeated exposure to oxamyl triggers an integrative neurotoxic response, driven by genotoxicity, oxidative stress, and neuroinflammation, that could trigger an increase in neurological and cognitive disorders. These findings emphasize the urgent need for confirmatory translational studies in human subjects to assess these changes and inform policy decisions regarding safe levels of usage and appropriate agricultural and public health practices.

Ferulic Acid Alleviates Radiation-Induced Immune Damage by Acting on JAK/STAT Signaling Pathway.

The disruption of hematopoietic and immune functions is a significant consequence of the long-term effects of radiation exposure. This study investigated the potential mechanisms by which ferulic acid (FA) acts as a radioprotective agent in mitigating radiation-induced immune damage. C57BL/6J mice were exposed to a dose of 6.0 Gy of 60Co γ irradiation. FA was administered at doses of 25, 50, and 100 mg/kg/d for 7 days before and 30 days following irradiation. We evaluated changes in peripheral blood cells, T and B lymphocytes, natural killer cells in the spleen, and hematopoietic stem/progenitor cells in the bone marrow (BM). Whole-genome transcriptome sequencing of BM was performed to explore potential mechanisms. FA administration resulted in a significant reduction in malonaldehyde levels (p < 0.0001), an increase in catalase and beta-nicotinamide adenine dinucleotide levels in serum (p < 0.05), and enhanced multipotent progenitors (p < 0.01) and common lymphoid progenitors (p < 0.05) in the BM. Additionally, there was an elevation in white blood cell levels, red blood cell levels, and hemoglobin levels in peripheral blood (p < 0.01). Transcriptome analysis indicated that FA reversed the radiation-induced expression of genes related to immunity and inflammation. Enzyme-linked immunosorbent assay experiments further demonstrated that FA reduced interleukin-6 levels in the BM and decreased JAK1, JAK2, and STAT3 protein content (p < 0.01). In conclusion, FA might mitigate hematopoietic and immune damage by modulating the JAK/STAT signaling pathway.