ACRYLONITRILE HAS DISTINCT HORMETIC EFFECTS ON ACETYLCHOLINESTERASE ACTIVITY IN MOUSE BRAIN AND BLOOD THAT ARE MODULATED BY ETHANOL

Acrylonitrile(AN) is a neurotoxin both in animals and humans, but its effects on acetylcholinesterase (AChE) activity remain controversial. This study aimed to determine the dose-response effects of AN on AChE activity and the modulatory role of ethanol pretreatment. A total of 144 Kunming mice were randomly divided into 18 groups: nine groups received 5% ethanol in their drinking water, and the remaining nine groups received regular tap water. One week later, both the ethanol and tap water only groups were given an intraperitoneal injection of AN at the following doses: 0 (control), 0.156, 0.3125, 0.625, 1.25, 2.5, 5, 10 or 20 mg AN/kg body weight. AChE activity was determined on whole blood and brain 24 h later. Blood AChE activity was higher in AN-injected mice than in controls at all doses. AChE activity in blood increased in a dose-dependent manner, peaking at 0.156 mg/kg, after which a gradual decrease ensued, displaying a β-typed dose-response relationship. In contrast, brain AChE activity, following a single AN injection, was consistently lower than in control mice, and continued to fall up to a dose of 0.313 mg/kg, and thereafter increased gradually with higher doses. Mice receiving a 20 mg/kg dose of AN exhibited AChE brain activity indistinguishable from that of control mice, demonstrating a typical U-typed dose-response relationship. The activity of AChE in the blood and brain of the AN + ethanol-treated groups displayed a shift to the right, and the magnitude of the decrease in AChE activity induced by AN was attenuated relative to the AN-only group. These results suggest that AN affects AChE activity in both mouse blood and brain in a hormetic manner. Pretreatment with ethanol modifies the effect of AN on AChE, indicating that parent AN has a more prominent role than its metabolites in modulating enzyme activity

From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles

Titanium dioxide nanoparticles (TiO2NPs) are widely produced and used nanoparticles. Yet, TiO2NP exposure may possess toxic effects to different cells and tissues, including the brain. Recent studies significantly expanded the understanding of the molecular mechanisms underlying TiO2NP neurotoxicity implicating a number of both direct and indirect mechanisms. In view of the significant recent progress in research on TiO2NP neurotoxicity, the objective of the present study is to provide a narrative review on the molecular mechanisms involved in its neurotoxicity, with a special focus on the studies published in the last decade. The existing data demosntrate that although TiO2NP may cross blood-brain barrier and accumulate in brain, its neurotoxic effects may be mediated by systemic toxicity. In addition to neuronal damage and impaired neurogenesis, TiO2NP exposure also results in reduced neurite outgrowth and impaired neurotransmitter metabolism, especially dopamine and glutamate. TiO2NP exposure was also shown to promote α-synuclein and β-amyloid aggregation, thus increasing its toxicity. Recent findings also suggest that epigenetic effects and alterations in gut microbiota biodiversity contribute to TiO2NP neurotoxicity. Correspondingly, in vivo studies demosntrated that TiO2NPs induce a wide spectrum of adverse neurobehavioral effects, while epidemiological data are lacking. In addition, TiO2NPs were shown to promote neurotoxic effects of other toxic compounds. Here we show the contribution of a wide spectrum of molecular mechanisms to TiO2NP-induced neurotoxicity; yet, the role of TiO2NP exposure in adverse neurological outcomes in humans has yet to be fully appreciated

HORMETIC EFFECTS OF ACUTE METHYLMERCURY EXPOSURE ON GRP78 EXPRESSION IN RAT BRAIN CORTEX

This study aims to explore the expression of GRP78, a marker of endoplasmic reticulum (ER) stress, in the cortex of rat brains acutely exposed to methylmercury (MeHg). Thirty Sprague-Dawley (SD) rats were randomly divided into six groups, and decapitated 6 hours (h) after intraperitoneal (i.p.) injection of MeHg (2, 4, 6, 8 or 10 mg/kg body weight) or normal saline. Protein and mRNA expression of Grp78 were detected by western blotting and real-time PCR, respectively. The results showed that a gradual increase in GRP78 protein expression was observed in the cortex of rats acutely exposed to MeHg (2, 4 or 6 mg/kg). Protein levels peaked in the 6 mg/kg group (p \u3c 0.05 vs. controls), decreased in the 8 mg/kg group, and bottomed below the control level in the 10 mg/kg group. Parallel changes were noted for Grp78 mRNA expression. It may be implied that acute exposure to MeHg induced hormetic dose-dependent changes in Grp78 mRNA and protein expression, suggesting that activation of ER stress is involved in MeHg-induced neurotoxicity. Low level MeHg exposure may induce GRP78 protein expression to stimulate endogenous cytoprotective mechanisms

Assessing hypertension and diabetes knowledge, attitudes and practices among residents in Akatsi South District, Ghana using the KAP questionnaire

ObjectiveLow awareness of hypertension and diabetes is a public health concern in Ghana. Assessing the general population’s behaviour via knowledge, attitude, and practice (KAP) will be invaluable in these diseases, where prevention and control need a lifelong commitment to a healthy lifestyle. Hence, our goal was to assess the behaviour of Akatsi South residents towards the diseases to assist health providers in implementing tailored intervention programs.MethodsThis was a population-based cross-sectional study with 150 adults (18–70 years) from November to December 2021. A semi-structured questionnaire with face-to-face interviews was used to obtain data. All variables in the model had descriptive statistics. The Chi-square (χ2) test was used to examine correlations between variables, and a value of p < 0.05 was considered statistically significant. The factors associated with checking blood sugar levels and blood pressure were determined using binary logistic regression.ResultsThe respondents’ mean age and BMI were 32.40 years (± 12.07) and 24.98 kg/m2 (± 2.36), respectively. Only 46.67% of the respondents frequently monitor their blood pressure and 17.33% their blood glucose (at least once a year). Less than half of those surveyed had a good knowledge of hypertension (42.7%) and diabetes (32.0%), whereas nearly 3/4 had poor attitudes regarding both conditions. A binary logistic regression analysis revealed that having a good attitude toward hypertension (exp B = 2.479, p = 0.036) and diabetes (exp B = 4.547, p = 0.009) were the participants’ strongest predictor of blood pressure and sugar level checks. However, being overweight (exp B = 0.046, p = 0.002,) or obese (exp B = 0.144, p = 0.034) negatively influenced the frequency with which our respondents checked their blood glucose levels.ConclusionIn the study, we found that the population generally has poor knowledge, which affects their behaviour (attitudes and practices) towards the diseases. To enable healthcare practitioners to reduce disease-associated mortality and morbidity in the future, frequent public health education and promotion about the conditions is critical to closing the knowledge gap

PM2.5 and Cardiovascular Diseases in the Elderly: An Overview

Background: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in the elderly and the ambient concentration of PM2.5 has been associated with several cardiovascular diseases. Methods: We describe the present state of planetary air pollution, analyze epidemiological studies linking PM2.5 and CVD, and discuss multiple pathophysiological mechanisms linking PM2.5 and CVD. Results: A few epidemiological studies show that the elderly appear specifically susceptible to adverse cardiovascular effects triggered by PM2.5 exposure. Plausible pathophysiological mechanisms include inflammatory dysfunction, oxidative stress, abnormal activation of the hemostatic system and disturbance of the autonomic nervous system. Conclusions: An in-depth knowledge of the chemical compounds, pathophysiological mechanisms, and epidemiological studies of PM2.5 are recommended to understand this important and modifiable factor contributing to geriatric CVD burden. We offer public health recommendations to reduce this preventable cause of disease and death

Analysis of Bearing Characteristics of Energy Pile Group Based on Exponential Model

Energy piles are an emerging energy technology for both structural and thermal purposes. To support structure load, piles are always used in groups with raft; however, the cost and complexity of field tests and numerical modelling limits the research on the bearing characteristics of energy pile group. In this paper, exponential model was applied to simulate the thermo-mechanical soil-pile interaction of energy pile group. Axial load transfer (τ-z) analysis was first performed to calculate the shear stress distribution in the soil, then matrix displacement method was introduced to determine the thermo-mechanical response of energy pile group. The validity of the analytical model was tested against field tests and numerical results. A case study was further performed to analyze the influence of thermal cycles and arrangement of thermally active piles on the bearing response of the whole pile group. Test results show that with the thermally activated pile in pile group, (1) differential settlement increases with thermal cycle numbers; (2) the axial force of thermally active pile increases during heating process and decreases during cooling process, and this trend varies for the surrounding nonthermal piles; (3) induced load on thermal pile increases with thermal cycles, but decreases for nonthermal piles. The proposed analytical model is expected to serve as a simple and convenient alternative for the preliminary analysis on the bearing characteristics of energy group pile

Latent Profile Analysis of Self-Supporting Ability among Rural Empty-Nesters in Northwestern China

The present study aimed to examine the multi-faceted self-supporting ability profiles of rural empty-nesters in northwestern China on the basis of the self-care ability, economic self-support ability, health self-maintenance ability, physical health self-maintenance ability, and psychological health self-maintenance ability using latent profile analysis. It identified the association of self-supporting ability profiles with demographic variables and sense of coherence. The analysis included 1066 participants (mean age = 70.2; SD = 4.3). The results of latent profile analysis identified three distinctive patterns of self-supporting ability―low physical health self-maintenance ability (C1, 20.5%), low psychological health self-maintenance ability (C2, 31.4%), and high social self-adaption ability (C3, 48.0%). The specific demographic variable age (p < 0.05), monthly income (p < 0.05), education level (p < 0.05), how often their children visit (p < 0.05), how often their children contact them (p < 0.05), whether they drink (p < 0.05), the frequency of physical exercise (p < 0.05), relationship with children (p < 0.05), relationship with neighbours (p < 0.05), medical insurance (p < 0.05), and the number of chronic diseases (p < 0.05) were significantly different among the identified three profiles. A statistically significant positive association existed between self-supporting ability profiles and sense of coherence (SOC) (p < 0.001). The results of multinomial logistic regression showed that a greater sense of coherence (SOC), age ≥ 80, monthly income (RMB) (RMB is the abbreviation for Renminbi) < 1000, a good relationship with neighbours, and one type of chronic disease were significantly associated with C1 when compared with C3 (p < 0.05). Furthermore, a greater SOC, their children visiting and contacting them many times per week or once per week were more significantly related to C2 than to C3 (p < 0.05). This study revealed three groups of self-supporting ability and its related predictors in empty-nesters. The predictors related to particular classes of self-supporting ability can provide information for targeted interventions to improve the self-supporting ability of empty-nesters living in rural areas

Fasting Enhances the Acute Toxicity of Acrylonitrile in Mice via Induction of CYP2E1

Cytochrome P450 2E1 (CYP2E1) plays an essential role in the susceptibility to acute acrylonitrile (AN)-induced toxicity. Here, we investigated the toxicity and mechanism of AN in fasting mice and potential underlying mechanisms. Convulsions, loss of righting reflex, and death 4 h after AN treatment were observed and recorded for each group of mice. Relative to ad lib-fed mice, 48 h fasting significantly increased the acute toxicity of AN, as noted by a more rapid onset of convulsions and death. In addition, fasting significantly enhanced CYP2E1-mediated oxidative metabolism of AN, resulting in increased formation of CN- (one of the end-metabolites of AN). Moreover, fasting decreased hepatic GSH content, abrogating the detoxification of GSH. However, trans-1,2-dichloroethylene (DCE), a CYP2E1 inhibitor, altered the level of hepatic CYP2E1 activity in response to fasting, reduced the acute toxic symptoms of AN and the content of CN- in AN-treated mice. These data establish that fasting predisposes to AN toxicity, attributable to induced CYP2E1 and reduced hepatic GSH