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Neuroendocrine contribution to sex-related variations in adverse air pollution health effects. 神经内分泌对空气污染不良健康影响的性别差异的影响。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-11-16 Epub Date: 2024-07-29 DOI: 10.1080/10937404.2024.2383637
Devin I Alewel, Urmila P Kodavanti

Air pollution exposure is ranked as a leading environmental risk factor for not only cardiopulmonary diseases but also for systemic health ailments including diabetes, reproductive abnormalities, and neuropsychiatric disorders, likely mediated by central neural stress mechanisms. Current experimental evidence links many air pollution health outcomes with activation of neuroendocrine sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal (HPA) stress axes associated with resultant increases in adrenal-derived hormone levels acting as circulating mediators of multi-organ stress reactions. Epidemiological and experimental investigations also demonstrated sex-specific responses to air pollutant inhalation, which may be attributed to hormonal interactions within the stress and reproductive axes. Sex hormones (androgens and estrogens) interact with neuroendocrine functions to influence hypothalamic responses, subsequently augmenting stress-mediated metabolic and immune changes. These neurohormonal interactions may contribute to innate sex-specific responses to inhaled irritants, inducing differing individual susceptibility. The aim of this review was to: (1) examine neuroendocrine co-regulation of the HPA axis by gonadal hormones, (2) provide experimental evidence demonstrating sex-specific respiratory and systemic effects attributed to air pollutant inhalation exposure, and (3) postulate proposed mechanisms of stress and sex hormone interactions during air pollution-related stress.

空气污染不仅是心肺疾病的主要环境风险因素,也是糖尿病、生殖异常和神经精神障碍等全身性疾病的主要环境风险因素,这可能是由中枢神经应激机制介导的。目前的实验证据表明,许多空气污染对健康的影响与神经内分泌交感-肾上腺-髓质和下丘脑-垂体-肾上腺(HPA)应激轴的激活有关,其结果是作为多器官应激反应循环介质的肾上腺衍生激素水平增加。流行病学和实验研究也表明,吸入空气污染物会对不同性别产生不同的反应,这可能归因于压力轴和生殖轴中激素的相互作用。性激素(雄性激素和雌性激素)与神经内分泌功能相互作用,影响下丘脑的反应,进而增强压力介导的新陈代谢和免疫变化。这些神经荷尔蒙的相互作用可能会导致对吸入性刺激物的先天性性别特异性反应,从而诱发不同的个体易感性。本综述旨在:(1) 研究性腺激素对 HPA 轴的神经内分泌共同调节作用;(2) 提供实验证据,证明吸入空气污染物对呼吸系统和全身系统的影响具有性别特异性;(3) 提出与空气污染有关的应激过程中应激和性激素相互作用的拟议机制。
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引用次数: 0
Local and systemic effects of microplastic particles through cell damage, release of chemicals and drugs, dysbiosis, and interference with the absorption of nutrients. 微塑料微粒通过细胞损伤、释放化学物质和药物、菌群失调以及干扰营养物质的吸收,对局部和全身产生影响。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-11-16 Epub Date: 2024-09-26 DOI: 10.1080/10937404.2024.2406192
Eleonore Fröhlich

Microplastic particles (MPs) have been detected in a variety of environmental samples, including soil, water, food, and air. Cellular studies and animal exposures reported that exposure to MPs composed of different polymers might result in adverse effects at the portal of entry (local) or throughout the body (systemic). The most relevant routes of particle uptake into the body are oral and respiratory exposure. This review describes the various processes that may contribute to the adverse effects of MPs. Only MPs up to 5 µm were found to cross epithelial barriers to a significant extent. However, MPs may also exert a detrimental impact on human health by acting at the epithelial barrier and within the lumen of the orogastrointestinal and respiratory tract. The potential for adverse effects on human health resulting from the leaching, sorption, and desorption of chemicals, as well as the impact of MPs on nutritional status and dysbiosis, are reviewed. In vitro models are suggested as a means of (1) assessing permeation, (2) determining adverse effects on cells of the epithelial barrier, (3) examining influence of digestive fluids on leaching, desorption, and particle properties, and (4) role of microbiota-epithelial cell interactions. The contribution of these mechanisms to human health depends upon exposure levels, which unfortunately have been estimated very differently.

在各种环境样本(包括土壤、水、食物和空气)中都检测到了微塑料颗粒(MPs)。细胞研究和动物接触报告显示,接触由不同聚合物组成的微塑料颗粒可能会对进入人体的入口(局部)或全身(全身)造成不良影响。颗粒摄入人体的最相关途径是口腔和呼吸道接触。本综述介绍了可能导致 MPs 负面影响的各种过程。研究发现,只有 5 微米以下的微粒能在很大程度上穿过上皮屏障。不过,MPs 也可能通过作用于上皮屏障以及口腔胃肠道和呼吸道内腔而对人体健康产生不利影响。本文综述了化学品的浸出、吸附和解吸可能对人体健康造成的不利影响,以及多孔质物质对营养状况和菌群失调的影响。建议将体外模型作为以下方面的一种手段:(1) 评估渗透性;(2) 确定对上皮屏障细胞的不利影响;(3) 检查消化液对浸出、解吸和颗粒特性的影响;(4) 微生物群-上皮细胞相互作用的作用。这些机制对人体健康的影响取决于暴露水平,遗憾的是,对暴露水平的估计却大相径庭。
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引用次数: 0
Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now! 将新方法(NAMs)数据纳入剂量反应评估:未来就是现在!
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-10-10 DOI: 10.1080/10937404.2024.2412571
En-Hsuan Lu, Ivan Rusyn, Weihsueh A Chiu

Regulatory dose-response assessments traditionally rely on in vivo data and default assumptions. New Approach Methods (NAMs) present considerable opportunities to both augment traditional dose-response assessments and accelerate the evaluation of new/data-poor chemicals. This review aimed to determine the potential utilization of NAMs through a unified conceptual framework that compartmentalizes derivation of toxicity values into five sequential Key Dose-response Modules (KDMs): (1) point-of-departure (POD) determination, (2) test system-to-human (e.g. inter-species) toxicokinetics and (3) toxicodynamics, (4) human population (intra-species) variability in toxicodynamics, and (5) toxicokinetics. After using several "traditional" dose-response assessments to illustrate this framework, a review is presented where existing NAMs, including in silico, in vitro, and in vivo approaches, might be applied across KDMs. Further, the false dichotomy between "traditional" and NAMs-derived data sources is broken down by organizing dose-response assessments into a matrix where each KDM has Tiers of increasing precision and confidence: Tier 0: Default/generic values, Tier 1: Computational predictions, Tier 2: Surrogate measurements, and Tier 3: Direct measurements. These findings demonstrated that although many publications promote the use of NAMs in KDMs (1) for POD determination and (5) for human population toxicokinetics, the proposed matrix of KDMs and Tiers reveals additional immediate opportunities for NAMs to be integrated across other KDMs. Further, critical needs were identified for developing NAMs to improve in vitro dosimetry and quantify test system and human population toxicodynamics. Overall, broadening the integration of NAMs across the steps of dose-response assessment promises to yield higher throughput, less animal-dependent, and more science-based toxicity values for protecting human health.

监管机构的剂量反应评估传统上依赖于体内数据和默认假设。新方法(NAMs)提供了大量机会,既能增强传统的剂量-反应评估,又能加快对缺乏数据的新化学品的评估。本综述旨在通过一个统一的概念框架来确定新方法的潜在用途,该框架将毒性值的推导划分为五个连续的关键剂量-反应模块(KDMs):(1) 出发点(POD)确定,(2) 试验系统对人类(如物种间)毒物动力学和 (3) 毒力动力学,(4) 人类群体(物种内)毒力动力学变异,以及 (5) 毒物代谢动力学。在使用几种 "传统 "剂量-反应评估来说明这一框架后,对现有的 NAM(包括硅学、体外和体内方法)可能适用于 KDM 的情况进行了综述。此外,"传统 "数据源和 NAMs 派生数据源之间错误的二分法被打破,剂量-反应评估被组织成一个矩阵,每个 KDM 都有精度和置信度不断提高的层级:第 0 层:默认值/通用值,第 1 层:计算预测,第 2 层:替代测量,第 3 层:直接测量。这些研究结果表明,尽管许多出版物都提倡在 KDM 中使用 NAM(1)用于 POD 测定和(5)用于人类毒代动力学,但建议的 KDM 和层级矩阵揭示了 NAM 在其他 KDM 中整合的更多直接机会。此外,还确定了开发 NAM 的关键需求,以改进体外剂量测定并量化测试系统和人群毒物动力学。总之,在剂量-反应评估的各个步骤中扩大对 NAM 的整合,有望产生更高的吞吐量、更少的动物依赖性和更科学的毒性值,从而保护人类健康。
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引用次数: 0
In vitro models to evaluate multidrug resistance in cancer cells: Biochemical and morphological techniques and pharmacological strategies. 评估癌细胞多药耐药性的体外模型:生化和形态学技术及药理学策略。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-10-03 DOI: 10.1080/10937404.2024.2407452
Maria Fernanda Madrid, Eleicy Nathaly Mendoza, Ana Lizeth Padilla, Celia Choquenaira-Quispe, Celina de Jesus Guimarães, João Victor de Melo Pereira, Francisco Washington Araújo Barros-Nepomuceno, Ingredy Lopes Dos Santos, Claudia Pessoa, Manoel Odorico de Moraes Filho, Danilo Damasceno Rocha, Paulo Michel Pinheiro Ferreira

The overexpression of ATP-binding cassette (ABC) transporters contributes to the failure of chemotherapies and symbolizes a great challenge in oncology, associated with the adaptation of tumor cells to anticancer drugs such that these transporters become less effective, a mechanism known as multidrug resistance (MDR). The aim of this review is to present the most widely used methodologies for induction and comprehension of in vitro models for detection of multidrug-resistant (MDR) modulators or inhibitors, including biochemical and morphological techniques for chemosensitivity studies. The overexpression of MDR proteins, predominantly, the subfamily glycoprotein-1 (P-gp or ABCB1) multidrug resistance, multidrug resistance-associated protein 1 (MRP1 or ABCCC1), multidrug resistance-associated protein 2 (MRP2 or ABCC2) and cancer resistance protein (ABCG2), in chemotherapy-exposed cancer lines have been established/investigated by several techniques. Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase assays to distinguish types of interaction with ABC transporters, (vi) morphology to detail phenotypic characteristics in transformed cells, (vii) molecular testing of resistance-related proteins (RT-qPCR) and (viii) 2D and 3D models, (ix) organoids, and (x) microfluidic technology. Then, in vitro models for detecting chemotherapy MDR cells to assess innovative therapies to modulate or inhibit tumor cell growth and overcome clinical resistance. It is noteworthy that different therapies including anti-miRNAs, antibody-drug conjugates (to natural products), and epigenetic modifications were also considered as promising alternatives, since currently no anti-MDR therapies are able to improve patient quality of life. Therefore, there is also urgency for new clinical markers of resistance to more reliably reflect in vivo effectiveness of novel antitumor drugs.

ATP结合盒(ABC)转运体的过度表达是化疗失败的原因之一,也是肿瘤学面临的一个巨大挑战,这与肿瘤细胞对抗癌药物的适应性有关,从而降低了这些转运体的有效性,这种机制被称为多药耐药性(MDR)。本综述旨在介绍最广泛使用的诱导和理解体外模型的方法,以检测多药耐药性(MDR)调节剂或抑制剂,包括用于化疗敏感性研究的生化和形态学技术。在化疗暴露的癌系中,MDR 蛋白(主要是多药耐药性糖蛋白-1(P-gp 或 ABCB1)亚家族、多药耐药性相关蛋白 1(MRP1 或 ABCCC1)、多药耐药性相关蛋白 2(MRP2 或 ABCC2)和抗癌蛋白(ABCG2))的过表达已通过多种技术建立/研究。在这些技术中,最常用的是:(i) 比色/荧光间接生物测定;(ii) 罗丹明和外流分析;(iii) 通过荧光显微镜和流式细胞仪检测 3,30 二甲基氧杂羰花青碘化物的释放,以测量 P-gp 功能和其他 ABC 转运体;(iv) 排除钙黄绿素-乙酰氧甲基酯、(v) ATPase 检测,以区分与 ABC 转运体相互作用的类型;(vi) 形态学,以详细了解转化细胞的表型特征;(vii) 耐药性相关蛋白的分子检测(RT-qPCR);(viii) 二维和三维模型;(ix) 器官组织;以及 (x) 微流体技术。然后,通过体外模型检测化疗 MDR 细胞,以评估调节或抑制肿瘤细胞生长、克服临床耐药性的创新疗法。值得注意的是,包括抗 miRNA、抗体药物共轭物(天然产品)和表观遗传修饰在内的不同疗法也被认为是有前景的替代疗法,因为目前还没有抗 MDR 疗法能够改善患者的生活质量。因此,迫切需要新的临床耐药性指标,以更可靠地反映新型抗肿瘤药物的体内疗效。
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引用次数: 0
An integrative exploration of environmental stressors on the microbiome-gut-brain axis and immune mechanisms promoting neurological disorders. 综合探讨环境压力对微生物组-肠-脑轴的影响以及促进神经系统疾病的免疫机制。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-10-02 Epub Date: 2024-07-12 DOI: 10.1080/10937404.2024.2378406
Hajar Heidari, David A Lawrence

The microbiome-gut-brain axis is altered by environmental stressors such as heat, diet, and pollutants as well as microbes in the air, water, and soil. These stressors might alter the host's microbiome and symbiotic relationship by modifying the microbial composition or location. Compartmentalized mutualistic microbes promote the beneficial interactions in the host leading to circulating metabolites and hormones such as insulin and leptin that affect inter-organ functions. Inflammation and oxidative stress induced by environmental stressors may alter the composition, distribution, and activities of the microbes in the microbiomes such that the resultant metabolite and hormone changes are no longer beneficial. The microbiome-gut-brain axis and immune adverse changes that may accompany environmental stressors are reviewed for effects on innate and adaptive immune cells, which may make host immunity less responsive to pathogens and more reactive to self-antigens. Cardiovascular and fluid exchanges to organs might adversely alter organ functionality. Organs, especially the brain, need a consistent supply of nutrients and clearance of debris; disruption of these exchanges by stressors, and involvement of gut microbiome are discussed regarding neural dysfunctions with Alzheimer's disease, autistic spectrum disorders, viral infections, and autoimmune diseases. The focus of this review includes the manner in which environmental stressors may disrupt gut microbiota leading to adverse immune and hormonal influences on development of neuropathology related to hyperhomocysteinemia, inflammation, and oxidative stress, and how certain therapeutics may be beneficial. Strategies are explored to lessen detrimental effects of environmental stressors on central and peripheral health navigated toward (1) understanding neurological disorders and (2) promoting environmental and public health and well-being.

微生物组-肠-脑轴会受到环境压力的改变,如高温、饮食、污染物以及空气、水和土壤中的微生物。这些压力可能会通过改变微生物的组成或位置来改变宿主的微生物组和共生关系。互利共生的微生物在宿主体内促进有益的相互作用,从而产生循环代谢物和激素,如影响器官间功能的胰岛素和瘦素。环境压力诱发的炎症和氧化压力可能会改变微生物群落中微生物的组成、分布和活动,从而导致代谢物和激素的变化不再有益。微生物组-肠-脑轴和免疫不良变化可能会伴随着环境应激因素而发生,这些变化对先天性和适应性免疫细胞的影响可能会使宿主免疫对病原体的反应减弱,而对自身抗原的反应增强。器官的心血管和体液交换可能会对器官功能产生不利影响。器官,尤其是大脑,需要持续的营养供应和碎片清除;压力因素会破坏这些交换,肠道微生物组的参与也会影响阿尔茨海默病、自闭症谱系障碍、病毒感染和自身免疫性疾病的神经功能。本综述的重点包括环境应激因素可能破坏肠道微生物群,导致免疫和激素对与高同型半胱氨酸血症、炎症和氧化应激有关的神经病理学发展产生不利影响的方式,以及某些治疗方法可能带来的益处。本研究探讨了减轻环境应激因素对中枢和外周健康有害影响的策略,旨在:(1)了解神经系统疾病;(2)促进环境和公共健康与福祉。
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引用次数: 0
Styrene lung cancer risk assessment: an alternative evaluation of human lung cancer risk assuming mouse lung tumors are potentially human relevant and operating by a threshold-based non-genotoxic mode of action. 苯乙烯肺癌风险评估:人类肺癌风险的替代评估,假设小鼠肺部肿瘤可能与人类相关,并通过基于阈值的非遗传毒性作用模式进行操作。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-10-02 Epub Date: 2024-07-26 DOI: 10.1080/10937404.2024.2380449
J S Bus, S Su, W Li, J E Goodman

Rodent inhalation studies indicate styrene is a mouse lung-specific carcinogen. Mode-of-action (MOA) analyses indicate that the lung tumors cannot be excluded as weakly quantitatively relevant to humans due to shared oxidative metabolites detected in rodents and humans. However, styrene also is not genotoxic following in vivo dosing. The objective of this review was to characterize occupational and general population cancer risks by conservatively assuming mouse lung tumors were relevant to humans but operating by a non-genotoxic MOA. Inhalation cancer values reference concentrations for respective occupational and general population exposures (RfCcar-occup and RfCcar-genpop) were derived from initial benchmark dose (BMD) modeling of mouse inhalation tumor dose-response data. An overall lowest BMDL10 of 4.7 ppm was modeled for lung tumors, which was further duration- and dose-adjusted by physiologically based pharmacokinetic (PBPK) modeling to derive RfCcar-occup/genpop values of 6.2 ppm and 0.8 ppm, respectively. With the exception of open-mold fiber reinforced composite workers not using personal protective equipment (PPE), the RfCcar-occup/genpop values are greater than typical occupational and general population human exposures, thus indicating styrene exposures represent a low potential for human lung cancer risk. Consistent with this conclusion, a review of styrene occupational epidemiology did not support a conclusion of an association between styrene exposure and lung cancer occurrence, and further supports a conclusion that the conservatively derived RfCcar-occup is lung cancer protective.

啮齿动物吸入研究表明,苯乙烯是一种小鼠肺部特异性致癌物。作用模式(MOA)分析表明,由于在啮齿类动物和人类体内检测到了共同的氧化代谢物,因此不能排除肺部肿瘤与人类有微弱的定量相关性。不过,苯乙烯在体内施用后也不会产生基因毒性。本综述的目的是通过保守假设小鼠肺部肿瘤与人类相关,但由非遗传毒性 MOA 作用,来描述职业和普通人群的癌症风险。通过对小鼠吸入肿瘤剂量反应数据进行初始基准剂量(BMD)建模,得出了职业和普通人群各自的吸入癌症值参考浓度(RfCcar-occup 和 RfCcar-genpop)。针对肺部肿瘤的总体最低 BMDL10 建模值为 4.7 ppm,通过基于生理学的药代动力学 (PBPK) 建模,进一步对持续时间和剂量进行调整,得出 RfCcar-occup/genpop 值分别为 6.2 ppm 和 0.8 ppm。除未使用个人防护设备 (PPE) 的开模纤维增强复合材料工人外,RfCcar-occup/genpop 值均高于典型的职业和普通人群人类接触值,因此表明苯乙烯接触对人类肺癌风险的潜在影响较低。与这一结论相一致的是,对苯乙烯职业流行病学的审查并不支持苯乙烯暴露与肺癌发生之间存在关联的结论,并进一步支持保守推导出的 RfCcar-occup 对肺癌具有保护作用的结论。
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引用次数: 0
Relevance and feasibility of principles for health and environmental risk decision-making. 健康和环境风险决策原则的相关性和可行性。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-17 Epub Date: 2024-05-14 DOI: 10.1080/10937404.2024.2338078
Yadvinder Bhuller, Raywat Deonandan, Daniel Krewski

Globally, national regulatory authorities are both responsible and accountable for health and environmental decisions related to diverse products and risk decision contexts. These authorities provided regulatory oversight and expedited market authorizations of vaccines and other therapeutic products during the COVID-19 pandemic. Regulatory decisions regarding such products and situations depend upon well-established risk assessment and management steps. The underlying processes supporting such decisions were outlined in frameworks describing the complex interactions between factors including risk assessment and management steps as well as principles which help guide risk decision-making. In 2022, experts in risk science proposed a set of 10 guiding principles, further examining the intersection and utility of these principles using 10 diverse risk contexts, and inviting a broader discourse on the application of these principles in risk decision-making. To add to this information, Canadian regulatory practitioners responsible for evaluating health and environmental risks and establishing policies convened at a Health Canada workshop on Principles for Risk Decision-Making. This review reports the results derived from this interactive engagement and provides a first pragmatic analysis of the relevance, importance, and feasibility of such principles for health and environmental risk decision-making within the Canadian regulatory context.

在全球范围内,国家监管机构对与不同产品和风险决策相关的健康和环境决策负责并承担责任。在 COVID-19 大流行期间,这些机构对疫苗和其他治疗产品进行了监管监督并加快了市场授权。有关此类产品和情况的监管决策取决于既定的风险评估和管理步骤。支持此类决策的基本流程在框架中进行了概述,描述了包括风险评估和管理步骤在内的各种因素之间复杂的相互作用,以及有助于指导风险决策的原则。2022 年,风险科学专家提出了一套 10 项指导原则,利用 10 种不同的风险背景进一步研究了这些原则之间的交叉和效用,并邀请各方就这些原则在风险决策中的应用展开更广泛的讨论。为了补充这些信息,加拿大负责评估健康和环境风险以及制定政策的监管从业人员参加了加拿大卫生部举办的 "风险决策原则 "研讨会。本综述报告了这一互动参与所产生的结果,并首次对这些原则在加拿大监管范围内用于健康和环境风险决策的相关性、重要性和可行性进行了务实分析。
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引用次数: 0
Review of environmental airborne pyrene/benzo[a]pyrene levels from industrial emissions for the improvement of 1-hydroxypyrene biomonitoring interpretation. 回顾工业排放物中的环境空气芘/苯并[a]芘水平,以改进 1-羟基芘生物监测解释。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-17 Epub Date: 2024-06-06 DOI: 10.1080/10937404.2024.2362632
Adrien Clauzel, Renaud Persoons, Anne Maître, Franck Balducci, Pascal Petit

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants of significant public health concern, with several that are highly toxic to humans, including some proven or suspected carcinogens. To account for the high variability of PAH mixtures encountered in occupational settings, adjusting urinary 1-hydroxypyrene (1-OHP) levels by the total airborne pyrene (PyrT)/benzo[a]pyrene (BaP) ratio is essential for human biomonitoring (HBM). Given the complexity and cost of systematically monitoring atmospheric levels, alternative approaches to simultaneous airborne and HBM are required. The aim of this review was to catalog airborne PyrT/BaP ratios measured during different industrial activities and recommend 1-OHP-dedicated biological guidance values (BGV). A literature search was conducted. Seventy-one studies were included, with 5619 samples pertaining to 15 industrial sectors, 79 emission processes, and 213 occupational activities. This review summarized more than 40 years of data from almost 20 countries and highlighted the diversity and evolution of PAH emissions. PyrT/BaP ratios were highly variable, ranging from 0.8 in coke production to nearly 40 in tire and rubber production. A single PyrT/BaP value cannot apply to all occupational contexts, raising the question of the relevance of defining a single biological limit value for 1-OHP in industrial sectors where the PyrT/BaP ratio variability is high. Based upon the inventory, a practical approach is proposed for systematic PAH exposure and risk assessment, with a simple frame to follow based upon specific 1-OHP BGVs depending upon the occupational context and setup of a free PAH HBM interactive tool.

多环芳烃(PAHs)是一种无处不在的污染物,对公众健康具有重大影响,其中有几种对人体有剧毒,包括一些已证实或疑似致癌物质。为了考虑到职业环境中 PAH 混合物的高变异性,根据总空气传播芘 (PyrT)/ 苯并[a]芘 (BaP) 比率调整尿液中 1- 羟基芘 (1-OHP) 的水平对于人体生物监测 (HBM) 至关重要。鉴于系统监测大气中芘含量的复杂性和成本,需要采用其他方法来同时进行空气传播和 HBM 监测。本综述旨在对不同工业活动中测得的空气传播 PyrT/BaP 比率进行编目,并推荐 1-OHP 专用生物指导值 (BGV)。我们进行了文献检索。其中包括 71 项研究,5619 个样本涉及 15 个工业部门、79 个排放过程和 213 项职业活动。该综述总结了来自近 20 个国家的 40 多年的数据,并强调了多环芳烃排放的多样性和演变。PyrT/BaP 比率变化很大,从焦炭生产中的 0.8 到轮胎和橡胶生产中的近 40。单一的 PyrT/BaP 值不可能适用于所有职业环境,这就提出了在 PyrT/BaP 比率变化较大的工业部门定义单一的 1-OHP 生物限值的相关性问题。在清单的基础上,提出了一种实用的方法,用于系统性多环芳烃暴露和风险评估,根据职业环境和免费多环芳烃 HBM 互动工具的设置,在特定 1-OHP 生物极限值的基础上建立一个简单的框架。
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引用次数: 0
The possible impacts of nano and microplastics on human health: lessons from experimental models across multiple organs. 纳米和微塑料对人体健康的可能影响:从跨多个器官的实验模型中汲取的经验教训。
IF 7.2 2区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-05-18 Epub Date: 2024-03-22 DOI: 10.1080/10937404.2024.2330962
Bernardo Lannes Monteiro Fontes, Lorena Cristina de Souza E Souza, Ana Paula Santos da Silva de Oliveira, Rodrigo Nunes da Fonseca, Marinaldo Pacifico Cavalcanti Neto, Cintia Rodrigues Pinheiro

The widespread production and use of plastics have resulted in accumulation of plastic debris in the environment, gradually breaking down into smaller particles over time. Nano-plastics (NPs) and microplastics (MPs), defined as particles smaller than 100 nanometers and 5 millimeters, respectively, raise concerns due to their ability to enter the human body through various pathways including ingestion, inhalation, and skin contact. Various investigators demonstrated that these particles may produce physical and chemical damage to human cells, tissues, and organs, disrupting cellular processes, triggering inflammation and oxidative stress, and impacting hormone and neurotransmitter balance. In addition, micro- and nano-plastics (MNPLs) may carry toxic chemicals and pathogens, exacerbating adverse effects on human health. The magnitude and nature of these effects are not yet fully understood, requiring further research for a comprehensive risk assessment. Nevertheless, evidence available suggests that accumulation of these particles in the environment and potential human uptake are causes for concern. Urgent measures to reduce plastic pollution and limit human exposure to MNPLs are necessary to safeguard human health and the environment. In this review, current knowledge regarding the influence of MNPLs on human health is summarized, including toxicity mechanisms, exposure pathways, and health outcomes across multiple organs. The critical need for additional research is also emphasized to comprehensively assess potential risks posed by degradation of MNPLs on human health and inform strategies for addressing this emerging environmental health challenge. Finally, new research directions are proposed including evaluation of gene regulation associated with MNPLs exposure.

塑料的广泛生产和使用导致塑料碎片在环境中积累,并随着时间的推移逐渐分解成更小的颗粒。纳米塑料(NPs)和微塑料(MPs)的定义分别是小于 100 纳米和 5 毫米的颗粒,它们能够通过摄入、吸入和皮肤接触等各种途径进入人体,因此引起了人们的关注。多项研究表明,这些微粒可能会对人体细胞、组织和器官造成物理和化学损伤,破坏细胞过程,引发炎症和氧化应激,并影响激素和神经递质的平衡。此外,微塑料和纳米塑料(MNPLs)可能携带有毒化学品和病原体,加剧对人类健康的不利影响。这些影响的程度和性质尚不完全清楚,需要进一步研究,以进行全面的风险评估。不过,现有证据表明,这些微粒在环境中的积累和人类的潜在摄入量令人担忧。为保护人类健康和环境,有必要采取紧急措施,减少塑料污染,限制人类与多金属颗粒的接触。在这篇综述中,总结了目前有关 MNPLs 对人类健康影响的知识,包括毒性机制、暴露途径和多个器官的健康结果。此外,还强调了开展更多研究的迫切需要,以便全面评估 MNPLs 降解对人类健康造成的潜在风险,并为应对这一新兴环境健康挑战的策略提供信息。最后,提出了新的研究方向,包括评估与 MNPLs 暴露相关的基因调控。
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引用次数: 0
Application of nanoformulations as a strategy to optimize chemotherapeutic treatment of glioblastoma: a systematic review. 应用纳米制剂作为优化胶质母细胞瘤化疗的策略:系统综述。
IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-05-18 Epub Date: 2024-03-13 DOI: 10.1080/10937404.2024.2326679
Victor Alves de Oliveira, Helber Alves Negreiros, Igor Gabriel Barbosa de Sousa, Layza Karyne Farias Mendes, João Pedro Alves Damaceno Do Lago, Athanara Alves de Sousa, Taline Alves Nobre, Irislene Costa Pereira, Felipe Cavalcanti Carneiro da Silva, Janildo Lopes Magalhães, João Marcelo de Castro E Sousa

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.

本综述旨在探讨纳米制剂作为优化胶质母细胞瘤治疗策略的进展,尤其侧重于靶向和控制肿瘤给药系统。本综述遵循 PRISMA 建议。这些研究是通过 2023 年 4 月在电子数据库 PubMed Central、Science Direct、Scopus 和 Web of Science 中使用等式描述符进行文献检索筛选出来的:(纳米胶囊或纳米制剂)和(胶质母细胞瘤)。收录的 47 项研究发表于 2011 年至 2023 年期间,目的是评估不同纳米制剂的应用情况,以优化化疗药物的给药,包括以前用于脑肿瘤治疗的替莫唑胺、卡莫司汀、长春新碱或顺铂,以及对另外 10 种药物的研究。数据显示,不同的基质可用作纳米载体,并利用功能化制剂改善化疗药物的内化。功能化是通过应用肽、微量营养素/维生素、抗体和 siRNAs 发展起来的。最后,本综述展示了纳米载体在胶质母细胞瘤模型中递送多种药物的实际和临床应用。开发这些纳米模型时,最好使用功能化配体制剂,这些制剂最好能与所携带的药物发挥协同作用。研究结果表明,纳米制剂前景广阔,是胶质母细胞瘤治疗创新和改进的最佳选择之一。
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引用次数: 0
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Journal of Toxicology and Environmental Health-Part B-Critical Reviews
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