Assessment of trace element and mineral levels in students from Turkmenistan in comparison to Iran and Russia.

THE OBJECTIVE: Of the present study was to assess essential trace element and mineral levels in serum, hair, and urine of healthy first-year students from Turkmenistan (n = 73) in comparison to students from Iran (n = 78) or Russia (n = 95). MATERIALS AND METHODS: Examination of foreign students was performed within two days after arrival to Russia during medical examination prior admission to RUDN University. Serum, hair, and urine trace element and mineral levels were assessed with inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: The data demonstrate that the levels of trace elements and minerals in students from Turkmenistan share high similarity to elemental profiles of students from Iran. In comparison to students from Russia, subjects originating from Iran and Turkmenistan are characterized by lower serum cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), molybdenum (Mo), selenium (Se), vanadium (V), zinc (Zn) levels, higher urinary Cr, Cu, Fe, Mn, V, and Zn, lower urinary Co and hair Mo, Se, and Zn content. Concomitantly, students from Turkmenistan were characterized by lower urinary Cr and Cu, serum Cu and V levels, higher circulating Zn concentration, as well as the lower hair Cr, Cu, iodine (I) and magnesium (Mg) content in comparison to Iranian subjects. The discriminant analysis demonstrated that hair, serum, and urinary trace element and mineral levels contributed to complete discrimination between the groups of students from different countries. CONCLUSIONS: The high similarity of trace element and mineral status of students from Turkmenistan and Iran is expected to be mediated by similar geochemical conditions in the bordering countries.

Medical application of laser-induced breakdown spectroscopy (LIBS) for assessment of trace element and mineral in biosamples: Laboratory and clinical validity of the method.

BACKGROUND: Biomedical application is based on the use of LIBS-derived data on chemical contents of tissues in diagnosis of diseases, forensic investigation, as well as a mechanism for providing online feedback for laser surgery. Although LIBS has certain advantages, the issue of correlation of LIBS-derived data on chemical element content in different human and animal tissues with other methods, and especially ICP-MS, remains pertinent. The objective of the present review was to discuss the application of laser-induced breakdown spectroscopy (LIBS) for elemental analysis of human biosamples or tissues from experimental models of human diseases. METHODS: A systematic search in the PubMed-Medline, Scopus, and Google Scholar databases using the terms laser-induced breakdown spectroscopy, LIBS, metals, trace elements, minerals, and names of particular chemical elements was performed up through 25 February, 2023. Of all extracted studies only those dealing with human subjects, human tissues, in vivo animal and in vitro cell line models of human diseases were reviewed in detail. RESULTS: The majority of studies revealed a wide number of metals and metalloids in solid tissues including teeth (As, Ag, Ca, Cd, Cr, Cu, Fe, Hg, Mg, Ni, P, Pb, Sn, Sr, Ti, and Zn), bones (Al, Ba, Ca, Cd, Cr, K, Mg, Na, Pb, Sr), and nails (Al, As, Ca, Fe, K, Mg, Na, P, Pb, Si, Sr, Ti, Zn). At the same time, LIBS was also used for estimation of trace element and mineral content in hair (Ca, Cu, Fe, K, Mg, Na, Zn), blood (Al, Ca, Co, Cd, Cu, Fe, Mg, Mn, Ni, Pb, Si, Sn, Zn), cancer tissues (Ca, Cu, Fe, Mg, K, Na, Zn) and other tissues. Single studies revealed satisfactory correspondence between quantitative LIBS and ICP-OES/MS data on the level of As (81-93 %), Pb (94-98 %), Cd (50-94 %) in teeth, Cu (97-105 %), Fe (117 %), Zn (88-117 %) in hair, Ca (97-99 %), Zn (90-95 %), and Pb (61-82 %) in kidney stones. LIBS also estimated specific patterns of trace element and mineral content associated with multiple pathologies, including caries, cancer, skin disorders, and other systemic diseases including diabetes mellitus type 2, osteoporosis, hypothyroidism, etc. Data obtained from in situ tissue LIBS analysis were profitably used for discrimination between tissue types. CONCLUSIONS: Taken together, the existing data demonstrate the applicability of LIBS for medical studies, although further increase in its sensitivity, calibration range, cross-validation, and quality control is required.

Utility of cockroach as a model organism in the assessment of toxicological impacts of environmental pollutants.

Environmental pollution is a global concern because of its associated risks to human health and ecosystem. The bio-monitoring of environmental health has attracted much attention in recent years and efforts to minimize environmental contamination as well as to delineate toxicological mechanisms related to toxic exposure are essential to improve the health conditions of both humans and animals. This review aims to substantiate the need and advantages in utilizing cockroaches as a complementary, non-mammalian model to further understand the noxious impact of environmental contaminants on humans and animals. We discuss recent advances in neurotoxicology, immunotoxicology, reproductive and developmental toxicology, environmental forensic entomotoxicology, and environmental toxicology that corroborate the utility of the cockroach (Periplaneta americana, Blaptica dubia, Blattella germanica and Nauphoeta cinerea) in addressing toxicological mechanisms as well as a sensor of environmental pollution. Indeed, recent improvements in behavioural assessment and the detection of potential biomarkers allow for the recognition of phenotypic alterations in cockroaches following exposure to toxic chemicals namely saxitoxin, methylmercury, polychlorinated biphenyls, electromagnetic fields, pharmaceuticals, polycyclic aromatic hydrocarbon, chemical warfare agents and nanoparticles. The review provides a state-of-the-art update on the current utility of cockroach models in various aspects of toxicology as well as discusses the potential limitations and future perspectives.

Assessment of intestinal injury of hexavalent chromium using a modified in vitro gastrointestinal digestion model.

Intestinal injury assessment of hexavalent chromium (Cr-VI) in humans is crucial for quantifying assessment of adverse health risk posed by the intake of Cr (VI)-contaminated water. To overcome the deficiency in simulating human gastric reduction and intestinal absorption, we modified the constituents of simulated gastric fluid in in vitro digestion method by adding reductants glutathione (18 µM) and ascorbic acid (180 µM), which incorporated with human intestinal epithelial model to construct an in vitro gastrointestinal digestion (IVGD) model for intestinal injury assessment. Cr-VI bioaccessibility results from IVGD model showed that weak gastric acidity significantly increased the intestinal accessible Cr-VI dose by 22.41-38.43 folds. The time-course intestinal absorption indicated prolongation of intestinal exposure destroyed the intestinal epithelium, and 24 h after Cr-VI treatment was a good time point to perform intestinal absorption and toxicity assessment. A series of cell-based bioassays provided initial warning of adverse effect, suggesting that epithelial integrity exhibited greatest sensitivity to Cr-VI exposure and might be used as a sensitive marker for the toxicity assessment of oral exposure to Cr-VI. Notably, this study provides a feasible strategy for delineation of Cr-VI biotransformation and intestinal injury following ingestion exposure, which contributes to address the toxicity data gap of low-dose exposure in humans and puts forward a reference for intestinal toxicity assessment of other chemicals.

Estimated IQ points and lifetime earnings lost to early childhood blood lead levels in the United States.

There is no safe detectable level of lead (Pb) in the blood of children. Blood lead levels (BLLs) at ages 6-24 months ≥2 µg/dL result in lost grade school intelligence quotient (IQ) points at ages 5-10 years. Black children continue to have the highest BLLs in the United States. Therefore, we examined currently undetermined racial/ethnic disparities in anticipated IQ points and associated lifetime earnings lost to early childhood blood lead. We conducted secondary analysis of infants with blood lead (in µg/dL) measured at ages 12-24 months by the cross-sectional National Health and Nutrition Examination Survey (NHANES) during 1999 to 2010. Nationally-representative estimates were produced using weighted simulation model. A total of 1241 infants were included from the NHANES sample (52% male; mean [SD] age, 18.5 [3.5] months; 25% Black [non-Hispanic], 42% Hispanic [any race], 5% Other/Multiracial, and 29% White [non-Hispanic]) after excluding 811 without BLL determinations. For national outcomes, Black infants experienced approximately 46-55% greater average estimated loss of grade school IQ points from blood lead than Hispanic or White infants (-1.78 IQ points vs. -1.15 and -1.21 respectively) with similar disparities in costs to expected lifetime earnings (-$47,116 USD vs. -$30,393 and -$32,356 respectively). Our estimated nationwide costs of IQ points lost to BLLs during this 12-year period totaled $554 billion ($46.2 billion/year), in which blood lead <5 µg/dL accounted for 74% of this total burden. We report two aspects of the substantial national costs attributable to lead exposure in just the second year of life alone, which disproportionately impact predominately African-American Black infants from continuing legacies of environmental racism in lead exposure. Our findings underscore the remarkably high costs from recognized hazards of blood lead even at the lowest levels and the importance of primary prevention regarding childhood lead exposure.

Whole body potassium as a biomarker for potassium uptake using a mouse model.

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight [Formula: see text] and [Formula: see text] g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males [Formula: see text] compared to females [Formula: see text]. We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 [Formula: see text] mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

Social injustice in environmental health: A call for fortitude.

The objective of this short paper is to call upon the scientific community to channel its attention to the duty and heedfulness of social justice issues. While recognized for decades the impact of social injustice on public health and its disproportionate effects on poorer communities, little has been done to systematically address it. Here, we provide several examples pertinent to the health outcomes associated with social injustice and call upon the scientific community to attend to the issue and antagonize those who attempt to subvert science and its role in ensuring social justice in health.

High throughput fluorimetric assessment of iron traffic and chelation in iron-overloaded Caenorhabditis elegans.

The nematode Caenorhabditis elegans (C. elegans) is a convenient tool to evaluate iron metabolism as it shares great orthology with human proteins involved in iron transport, in addition to being transparent and readily available. In this work, we describe how wild-type (N2) C. elegans nematodes in the first larval stage can be loaded with acetomethoxycalcein (CAL-AM) and study it as a whole-organism model for both iron speciation and chelator permeability of the labile iron pool (LIP). This model may be relevant for high throughput assessment of molecules intended for chelation therapy of iron overload diseases.

Application of cell-based biological bioassays for health risk assessment of PM2.5 exposure in three megacities, China.

The determination of PM2.5-induced biological response is essential for understanding the adverse health risk associated with PM2.5 exposure. In this study, we conducted cell-based bioassays to measure the toxic effects of PM2.5 exposure, including cytotoxicity, oxidative stress, genotoxicity and inflammatory response. The concentration-response relationship was analyzed by benchmark dose (BMD) modeling and the BMDL10 was used to estimate the biological potency of PM2.5 exposure. PM2.5 samples were collected from three typical megacities of China (Beijing, BJ; Wuhan, WH; Guangzhou, GZ) in typical seasons (winter and summer). The total PM, water-soluble fractions (WSF), and organic extracts (OE) were prepared and subjected to examination of toxic effects. The biological potencies for cytotoxicity, oxidative stress and genotoxicity were generally higher in winter samples, while the inflammatory potency of PM2.5 was higher in summer samples. The relative health risk (RHR) was determined by integration of the biological potencies and the cumulative exposure level, and the ranks of RHR were BJ-W > WH-W > BJ-S > WH-S > GZ-W > GZ-S. Notably, we note that different PM2.5 compositions were associated with distinct biological effects, and the health effects distribution of PM2.5 varied in regions and seasons. These findings demonstrate that the approach of integrated cell-based bioassays could be used for the evaluation of health effects of PM2.5 exposure.

Disparity in Risk Factor Severity for Early Childhood Blood Lead among Predominantly African-American Black Children: The 1999 to 2010 US NHANES.

There is no safe detectable level of lead (Pb) in the blood of young children. In the United States, predominantly African-American Black children are exposed to more Pb and present with the highest mean blood lead levels (BLLs). However, racial disparity has not been fully examined within risk factors for early childhood Pb exposure. Therefore, we conducted secondary analysis of blood Pb determinations for 2841 US children at ages 1-5 years with citizenship examined by the cross-sectional 1999 to 2010 National Health and Nutrition Examination Survey (NHANES). The primary measures were racial disparities for continuous BLLs or an elevated BLL (EBLL) ≥5 µg/dL in selected risk factors between non-Hispanic Black children (n = 608) and both non-Hispanic White (n = 1208) or Hispanic (n = 1025) children. Selected risk factors included indoor household smoking, low income or poverty, older housing built before 1978 or 1950, low primary guardian education <12th grade/general education diploma (GED), or younger age between 1 and 3 years. Data were analyzed using a regression model corrected for risk factors and other confounding variables. Overall, Black children had an adjusted +0.83 µg/dL blood Pb (95% CI 0.65 to 1.00, p < 0.001) and a 2.8 times higher odds of having an EBLL ≥5 µg/dL (95% CI 1.9 to 3.9, p < 0.001). When stratified by risk factor group, Black children had an adjusted 0.73 to 1.41 µg/dL more blood Pb (p < 0.001 respectively) and a 1.8 to 5.6 times higher odds of having an EBLL ≥5 µg/dL (p ≤ 0.05 respectively) for every selected risk factor that was tested. For Black children nationwide, one in four residing in pre-1950 housing and one in six living in poverty presented with an EBLL ≥5 µg/dL. In conclusion, significant nationwide racial disparity in blood Pb outcomes persist for predominantly African-American Black children even after correcting for risk factors and other variables. This racial disparity further persists within housing, socio-economic, and age-related risk factors of blood Pb outcomes that are much more severe for Black children.

An evaluation framework for new approach methodologies (NAMs) for human health safety assessment.

The need to develop new tools and increase capacity to test pharmaceuticals and other chemicals for potential adverse impacts on human health and the environment is an active area of development. Much of this activity was sparked by two reports from the US National Research Council (NRC) of the National Academies of Sciences, Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007) and Science and Decisions: Advancing Risk Assessment (2009), both of which advocated for "science-informed decision-making" in the field of human health risk assessment. The response to these challenges for a "paradigm shift" toward using new approach methodologies (NAMS) for safety assessment has resulted in an explosion of initiatives by numerous organizations, but, for the most part, these have been carried out independently and are not coordinated in any meaningful way. To help remedy this situation, a framework that presents a consistent set of criteria, universal across initiatives, to evaluate a NAM's fit-for-purpose was developed by a multi-stakeholder group of industry, academic, and regulatory experts. The goal of this framework is to support greater consistency across existing and future initiatives by providing a structure to collect relevant information to build confidence that will accelerate, facilitate and encourage development of new NAMs that can ultimately be used within the appropriate regulatory contexts. In addition, this framework provides a systematic approach to evaluate the currently-available NAMs and determine their suitability for potential regulatory application. This 3-step evaluation framework along with the demonstrated application with case studies, will help build confidence in the scientific understanding of these methods and their value for chemical assessment and regulatory decision-making.

Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study.

BACKGROUND: The objective of this pilot study was to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) status (hair, serum, and urine) and speciation (serum) in Parkinson's disease (PD) patients. METHODS: A pilot study involving a total of 27 subjects (13 PD patients, 14 controls) was performed. Serum, urine, and hair metal content was assessed using ICP-MS. Speciation analysis of Cu, Zn, Fe, and Mn was performed using a hybrid HPLC-ICP-MS system. RESULTS: Group comparisons did not reveal any significant group difference in serum Cu, Zn, Fe, and Mn total metal level between PD patients and controls. Speciation analysis revealed a significant decrease in Cu/ceruloplasmin copper in association with elevation of low-molecular weight species (amino acids)-bound copper. It is proposed that in PD, binding of Cu(II) ions to ceruloplasmin is reduced and free copper ions coordinate with low molecular weight ligands. The level of Mn-albumin complexes in PD patients was more than 4-fold higher as compared to the respective value in the control group. The observed difference may be considered as a marker of redistribution between high and low molecular weight ligands. CONCLUSIONS: Metal speciation is significantly affected in serum of PD-patients. These findings are indicative of the potential role of metal metabolism and PD pathogenesis, although the exact mechanisms of such associations require further detailed studies.

The development of a cell-based model for the assessment of carcinogenic potential upon long-term PM2.5 exposure.

To assess the carcinogenic potential of PM2.5 exposure, we developed a cell-based experimental protocol to examine the cell transformation activity of PM2.5 samples from different regions in China. The seasonal ambient PM2.5 samples were collected from three megacities, Beijing (BJ), Wuhan (WH), and Guangzhou (GZ), from November 2016 to October 2017. The mean concentrations of PM2.5 were much higher in the winter season (BJ: 109.64 µg/m3, WH: 79.99 µg/m3, GZ: 49.99 µg/m3) than that in summer season (BJ: 42.40 µg/m3, WH: 25.82 µg/m3, GZ: 19.82 µg/m3). The organic extracts (OE) of PM2.5 samples from combined summer (S) (June, July, August) or winter (W) (November, December, January) seasons were subjected to characterization of chemical components. We treated human bronchial epithelial (HBE) cells expressing CYP1A1 (HBE-1A1) with PM2.5 samples at doses ranging from 0 to 100 µg/mL (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100 µg/mL) and determined the phenotype of malignant cell transformation. A dose-response relationship was analyzed by benchmark dose (BMD) modeling, and the potential were indicated by BMDL10. The order of the carcinogenic risk of seasonal PM2.5 samples from high to low was BJ-W, WH-W, GZ-W, WH-S, BJ-S, and GZ-S. Notably, we found that the alteration in the lung cancer-related biomarkers, KRAS, PTEN, p53, c-Myc, PCNA, pAKT/AKT, and pERK/ERK was congruent with the activity of cell transformation and the content of specific components of polycyclic aromatic hydrocarbon (PAHs) bound to PM2.5. Taken together, we have successfully developed a cell-based alternative model for the evaluation of potent carcinogenicity upon long-term PM2.5 exposure.

New tools for the quantitative assessment of prodrug delivery and neurotoxicity.

Systemic off-target toxicities, including neurotoxicity, are prevalent side effects in cancer patients treated with a number of otherwise highly efficacious anticancer drugs. In the current study, we have: (1) developed a new analytical metric for the in vivo preclinical assessment of systemic toxicities/neurotoxicity of new drugs and delivery systems; and (2) evaluated, in mice, the in vivo efficacy and toxicity of a versatile and modular NanoDendron (ND) drug delivery and imaging platform that we recently developed. Our paclitaxel-carrying ND prodrug, ND(PXL), is activated following proteolytic cleavage by MMP9, resulting in localized cytotoxic chemotherapy. Using click chemistry, we combined ND(PXL) with a traceable beacon, ND(PB), yielding ND(PXL)-ND(PB) that functions as a theranostic compound. In vivo fluorescence FRET imaging of this theranostic platform was used to confirm localized delivery to tumors and to assess the efficiency of drug delivery to tumors, achieving 25-30% activation in the tumors of an immunocompetent mouse model of breast cancer. In this model, ND-drug exhibited anti-tumor efficacy comparable to nab-paclitaxel, a clinical formulation. In addition, we combined neurobehavioral metrics of nociception and sensorimotor performance of individual mice to develop a novel composite toxicity score that reveals and quantifies peripheral neurotoxicity, a debilitating long-term systemic toxicity of paclitaxel therapy. Importantly, mice treated with nab-paclitaxel developed changes in behavioral metrics with significantly higher toxicity scores indicative of peripheral neuropathy, while mice treated with ND(PXL) showed no significant changes in behavioral responses or toxicity score. Our ND formulation was designed to be readily adaptable to incorporate different drugs, imaging modalities and/or targeting motifs. This formulation has significant potential for preclinical and clinical tools across multiple disease states. The studies presented here report a novel toxicity score for assessing peripheral neuropathy and demonstrate that our targeted, theranostic NDs are safe and effective, providing localized tumor delivery of a chemotherapeutic and with reduced common neurotoxic side-effects.

Manganese exposure among smelting workers: blood manganese-iron ratio as a novel tool for manganese exposure assessment.

Unexposed control subjects (n = 106), power distributing and office workers (n = 122), and manganese (Mn)-exposed ferroalloy smelter workers (n = 95) were recruited to the control, low and high groups, respectively. Mn concentrations in saliva, plasma, erythrocytes, urine and hair were significantly higher in both exposure groups than in the controls. The Fe concentration in plasma and erythrocytes, however, was significantly lower in Mn-exposed workers than in controls. The airborne Mn levels were significantly associated with Mn/Fe ratio (MIR) of erythrocytes (eMIR) (r = 0.77, p < 0.01) and plasma (pMIR) (r = 0.70, p < 0.01). The results suggest that the MIR may serve as a useful biomarker to distinguish Mn-exposed workers from the unexposed, control population.

Chapter 8 - Nanoparticles: Transport across the olfactory epithelium and application to the assessment of brain function in health and disease.

The exciting advances within nanotechnology are beginning to be harnessed by the medical field. Nanoparticles have been used for drug delivery into the brain and have been explored for imaging, sensing, and analytical purposes. The science of nanoparticles encompasses a vast array of biological, chemical, physical, and engineering research, different aspects of which are specifically addressed in each of the chapters of this volume. Nanomaterials such as nanospheres, nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots (Qdots) are at the forefront of scientific attention, as they provide new consumer products and advance the scientific development of novel analytical tools in medicine and in the physical sciences. This chapter will briefly survey some aspects of nanoparticle biology focusing on the following: (1) the role of olfactory nanoparticle transport into the central nervous system (CNS), both as a potential route for effective drug delivery and as a route for the passage of noxious substances into the brain proper; (2) nanoparticles as sensors of cell function and toxicity; and (3) some adverse effects of nanoparticles on the dysregulation of brain redox status.

Neurotoxicology: principles and considerations of in vitro assessment.

Neurotoxicology is an exciting area of science, not only because of the importance of toxic injury to the nervous system in human disease, but also because specific toxicants have served as invaluable tools for the advancement of our knowledge of "normal" neurobiological processes. In fact, much of our understanding of the organisation and function of the nervous system is based on observations derived from the actions of neurotoxicants. This paper addresses various physiological aspects behind the exquisite sensitivity of the nervous system to toxic agents, including the privileged status of the nervous system vis-a-vis blood-brain barrier function, the extensions of the nervous system over space and the requirements of cells with such a complex geometry, and the transmission of information across extracellular space. In addition, in vitro models and their utility in the assessment of neurotoxicological outcome are discussed, with reference to both their advantages and disadvantages.