Behavioural impairment and oxidative stress by acute exposure of zebrafish to a commercial formulation of tebuconazole

Tebuconazole is a systemic follicular fungicide known to cause diverse problems in non-target organisms namely associated to the pure active ingredient. As such, the objective of this work was to evaluate developmental changes induced by a tebuconazole commercial formulation to a non-target animal model. Zebrafish embryos at ± 2 h post-fertilization were exposed to tebuconazole wettable powder concentrations (0.05, 0.5 and 5 mg L^-1) for 96 h with developmental toxicity assessed throughout the exposure period and biochemical parameters evaluated at the end of the exposure. Behavioural assessment (spatial exploration and response to stimuli) was conducted 24 h after the end of the exposure. While no developmental and physiological alterations were observed, exposure to tebuconazole resulted in an increased generation of reactive oxidative species at the 0.05 and 0.5 mg L^-1 concentrations and a decreased GPx activity at the 0.5 mg L^-1 concentration suggesting a potential protection mechanism. There was also a change in the avoidance-escape behaviour supporting an anxiolytic effect suggesting possible alterations in the central nervous system development demanding further studies.     

Sparkling plastic: Effects of exposure to glitter on the Mediterranean mussel Mytilus galloprovincialis

Microbeads and fragments have been widely studied, while glitter remains neglected by the literature although found in a variety product (e.g., body paints, nail polish, cosmetics, craft products). The main aim of this study was to assess the effects of different types and concentrations of glitter particles on Mytilus galloprovincialis after 7 days of exposure. The experiment was divided into a preliminary test and a confirmatory test. Our findings support the hypothesis for a link between concentration and type of glitter particles, percentage of recovery and oxidative stress in M. galloprovincialis. There was a significant correlation between particle length and percentage of particles recovered in water, suggesting that the digestive tract of M. galloprovincialis retains smaller particles more. In addition, we noted an increase in antioxidant defense induced by smaller particles. Moreover, certain types of glitter crumbled and shortened in length, resulting in higher levels of oxidative stress biomarkers. Finally, the star-shaped glitter particles had a different effect on oxidative stress biomarkers. Further studies are needed to clarify the toxic effects of glitter on aquatic organisms and to quantify its proportion to other microplastics in the environment.     

女性压力性尿失禁风险预测的研究进展

综述女性压力性尿失禁(stress urinary incontinence,SUI)风险预测的研究进展。指出女性SUI风险预测相关文献普遍存在风险预测工具和指标缺乏临床大样本验证,指标、纳入人群不统一的现象,风险预测模型存在构建过程未按报告规范进行,未进行完整的模型验证以及模型性能评价指标不规范的情况。未来研究可以在现有风险预测工具或模型的基础上进行改进、完善,以期为女性SUI风险预测提供参考。     

Case Report: Transient Stress Hyperglycemia in the Patient With ST-Elevation Myocardial Infarction

Transient stress hyperglycemia in the setting of acute myocardial infarction is a frequent phenomenon. Its transient nature should not dissuade the clinician from management of elevated blood glucose in a patient after an ST-elevation myocardial infarction. This case presents an adult patient after an ST-elevation myocardial infarction with transient stress hyperglycemia and the evidence used to identify optimal pharmacologic management and secondary prevention.     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Mobile daily diaries to characterize stressors and acute health symptoms in an environmental justice neighborhood

Low-income communities and communities of color face multiple, cumulative environmental and social burdens. Methods development in environmental justice research has largely focused on spatial and quantitative approaches. Less attention has been paid to developing methodologies that help collect information on everyday stressors and quality of life experiences for residents in overburdened communities. Mixed methods approaches can be one way to structure study designs that help consider how residents experience environmental and socioeconomic impacts in a localized community context. In neighborhoods burdened by cumulative stressors, traditional cross-sectional epidemiological research designs can also be challenging, as well as limited or narrow in their application. However, repeat sampling of measures within a vulnerable population can approach a quasi-experimental design and help consider variations within residents in a single neighborhood as well as better parse relationships between exposures and outcomes. Through a community-academic partnership with university partners, local community partners, and a local promotores de salud (community health workers) network, we pilot tested a novel mobile daily diary approach in both English and Spanish in an urban, predominantly immigrant community in South Los Angeles as a potential method to collect information on daily stress, environmental quality, and health status/symptoms. We collected resident responses via a once per day 7-day SMS/text messaging survey. We sought to gather granular data on daily resident experiences of air pollution and environmental hazards. Residents reported acute health symptoms and stressors, with repeat measures demonstrating how residents might rank, categorize, or cope with stressors. We find that residents in environmental justice communities record variation in their daily diary responses and document changes in environmental quality, stressors, and odors. Refining this type of method could enable a more rigorous examination of co-occurrences of environmental quality and acute health symptoms. This approach supports the inclusion of residents in the research process and helps more systematically integrate open-ended environmental health relevant data in environmental justice efforts. Used with measured data such as air monitoring or health measures, mixed methods generated data can help support efforts that aim to alleviate sources of daily stress, alongside efforts to reduce overall pollution burdens. Mobile daily diaries can be one way to capture variable responses to environmental quality, acute health symptoms, and stressors.     

Effects of the Cerebral Aneurysm Treatment Method on Coil Packing Density and Its Relationship with the Ostium Area

PurposeTo test the following hypotheses: (a) balloon or stent assistance increases coil packing density (CPD) in the endovascular treatment of intracranial aneurysms, and (b) CPD correlates to ostium area (OA) and aneurysm volume (AV).Materials and MethodsThis retrospective study included 60 aneurysms (54 ruptured and 6 unruptured) treated with simple coiling (SC) (n = 18), balloon-assisted coiling (BAC) (n = 7), or stent-assisted coiling (SAC) (n = 35) at the authors’ institution between August 2017 and December 2019. AV and OA measurements were obtained from 3-dimensional digital subtraction angiography images using commercial software. Coil sizes were retrieved from patient files, and coil volume (CV) measurements were obtained from https://www.angiocalc.com/. Analysis of covariance, multivariate covariance analysis, and Pearson correlation analyses were performed.ResultsThe median value for AV, CV, CPD, and OA was 63.4 mm³ (range, 5.5–1,771.4 mm³), 23.13 mm³ (range, 2.03–296.95 mm³), 33.29% (range, 13.41%–81.02%), and 10.7 mm² (range, 2.7–49.9 mm²), respectively. Multivariate analysis showed that the CPD values were not significantly different among the treatment groups, although OA significantly differed between the SC and SAC groups (P < .05). Pearson correlations showed that similar to AV, OA was negatively correlated with CPD (r = ?0.321, P < .05).ConclusionsThe CPD value in cerebral aneurysms treated with BAC or SAC did not differ from that in aneurysms treated with SC.     

阿克替苷通过激活血红素加氧酶-1抑制H_(2)O_(2)诱导的视网膜神经节细胞氧化损伤北大核心

目的研究阿克替苷对视网膜神经节细胞(RGC-5)的保护作用及其机制。方法将RGC-5细胞分为对照组、H_(2)O_(2)组、阿克替苷+H_(2)O_(2)组(1μmol·L^(-1)、10μmol·L^(-1)、30μmol·L^(-1)阿克替苷分别预处理细胞2 h),MTT法检测各组细胞活力;后续实验阿克替苷+H_(2)O_(2)组选择阿克替苷30μmol·L^(-1)作为治疗浓度,荧光探针H2DCF-DA检测活性氧(ROS)产生和罗丹明123检测线粒体膜电位,Western blot检测各组细胞中Bcl-2、Bcl-2/Bax、半胱氨酸蛋白酶-3(Caspase-3)蛋白表达。机制研究中首先用不同浓度阿克替苷单独处理RGC-5细胞24 h,Western blot检测血红素加氧酶-1(HO-1)蛋白表达水平,进一步锌原卟啉(ZnPP)预处理RGC-5细胞1 h,而后30μmol·L^(-1)阿克替苷单独预处理后与200μmol·L^(-1)H_(2)O_(2)共孵育24 h,通过MTT法测定细胞活力。结果与对照组相比,H_(2)O_(2)组中细胞活力明显降低(P<0.01)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组中10μmol·L^(-1)、30μmol·L^(-1)阿克替苷预处理可显著提高细胞活力(P<0.05、P<0.01)。与对照组相比,H_(2)O_(2)组RGC-5细胞ROS生成明显增加,线料体膜电位显著降低,同时Bcl-2/Bax比值降低和Caspase-3蛋白相对表达量增加(均为P<0.05)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组RGC-5细胞ROS生成减少,线粒体膜电位增加,Bcl-2/Bax比值提高,Caspase-3蛋白相对表达量减少(均为P<0.05)。与阿克替苷未处理组相比,阿克替苷剂量依赖性诱导HO-1蛋白的表达,与阿克替苷+H_(2)O_(2)组相比,加入ZnPP后细胞活力降低(P<0.01),说明HO-1抑制剂ZnPP降低了阿克替苷对H_(2)O_(2)损伤的抑制作用。结论阿克替苷能够通过上调HO-1表达抑制H_(2)O_(2)诱导的RGC-5氧化应激损伤。