Search Results (63)

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event. Herein, we conducted a quantitative structure–activity relationship analysis using the U.S. Food and Drug Administration Adverse Drug Reaction Database System (FAERS) and machine learning to construct a drug prediction model for MRONJ induction based solely on chemical structure information. Methods: A total of 4815 drugs from FAERS were evaluated, including 70 and 139 MRONJ-positive and MRONJ-negative drugs, respectively, identified based on reporting odds ratios, Fisher’s exact tests, and ≥100 total adverse event reports. Then, we calculated 326 chemical structure descriptors for each drug and compared three supervised learning algorithms (random forest, gradient boosting, and artificial neural networks). We also compared the number of chemical structure descriptors (5, 6, 7, 8, 9, 10, 20, and 30 descriptors). Results: We indicated that the MRONJ prediction model using an artificial neural network algorithm and eight descriptors achieved the highest validation receiver operating characteristic curve value of 0.778. Notably, the total polar surface area (ASA_P) was among the top-ranking descriptors, and MRONJ-positive drugs such as bisphosphonates and anticancer drugs showed high values. Our final model demonstrated a balanced accuracy of 0.693 and a specificity of 0.852. Conclusions: In this study, our MRONJ-inducing drug prediction model identified drugs with polar surface area properties as potential causes of MRONJ. This study demonstrates a promising approach for predicting MRONJ risk, which could enhance drug safety assessment and streamline drug screening in clinical and preclinical settings. Full article

Gastric cancer (GC) ranks as one of the most prevalent malignant tumors globally. The subtle manifestation of its early-stage symptoms often results in many GC patients being diagnosed at a late or advanced stage, thereby posing significant obstacles to the effectiveness of chemotherapy treatments. Therefore, identifying early biomarkers for GC is crucial. In recent years, an increasing number of studies have highlighted the pivotal role that aging plays in the progression of cancer. Among the various proteins involved, Cytoskeleton-associated protein 2 (CKAP2) emerges as a crucial player in controlling cell proliferation, regulating mitosis and cell division, and exerting a significant influence on the aging process. We employed a bioinformatics approach to assess the causal association between aging-related genes and GC and explore the potential significance of CKAP2 in GC by analyzing data sourced from various repositories, including Genotype Tissue Expression (GTEx), GWAS Catalog, The Database of Cell Senescence Genes (CellAge), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), and the Comparative Toxicology Genome Database (CTD). Our research summarized the causal relationship between CKAP2 expression and the development risk of GC, differential expression in GC, the relationship with the prognosis of GC, genetic correlation, functional analysis, and immune cell infiltration, and explored the interaction of CKAP2 and chemical substances. The findings revealed that an elevation in CKAP2 expression correlated with a reduced likelihood of developing GC. There was a significant difference in the expression of CKAP2 between GC and normal patients. Specifically, there was higher expression in GC compared to normal patients. In addition, CKAP2 has been proven to have diagnostic value in GC, and elevated levels of CKAP2 expression are indicative of a more favorable prognosis. Immune infiltration analysis revealed the relationship between CKAP2 and tumor immune microenvironment, while the Comparative Toxicology Genome Database (CTD) identified a small molecule compound that may target CKAP2. In summary, through comprehensive multivariate analyses, we identified and validated the potential role that CKAP2 may play in GC. Therefore, CKAP2 shows potential as an indicator for both the diagnosis and prognosis of GC, making it worthy of further clinical investigation. Full article

A nanomaterial life-cycle risk assessment (Nano LCRA) was conducted for second-generation functionalized cellulose nanomaterials (CNs) in five case studies, including applications in water filtration, food contact packaging (including as an additive and coating), and food additives, to identify and prioritize potential occupational, health, consumer, and environmental risks. Exposure scenarios were developed and ranked for each product life-cycle stage. A Safer-by-Design Toolbox (SbD Toolbox) representing a compendium of high-throughput physical, chemical, and toxicological new approach methodologies (NAMs) was used for a screening-level hazard assessment. Overall, risks identified for the CN-enabled products were low. Of the exposure scenarios, occupational inhalation exposures during product manufacturing and application ranked the highest. Despite differences in chemistry and morphology, the materials behaved similarly in oral, dermal, and inhalation models, supporting their grouping and read-across. The screening-level hazard assessment identified potential lung inflammation associated with CN exposure, and a review of the literature supported this funding, suggesting CNs behave as poorly soluble, low-toxicity dusts with the potential to irritate the lung. Key research gaps to reduce uncertainty include evaluating long-term, low-dose exposures typical of the workplace, as well as the potential release and toxicity of CN-containing composite particles. Full article

This study focuses on identifying key factors that companies should prioritize to prevent chemical accidents from an ESG (Environmental, Social, and Governance) perspective. ESG provides insight into corporate sustainability by comprehensively considering both external impacts and internal risks. To achieve this, this study applied a scoring approach based on double materiality, assessing both internal and external impacts. The assessment process involved data collection, categorization of accident causes, score calculation, and prioritization of safety management items. Data from chemical accident statistics revealed that mechanical integrity, human factors, and preventive maintenance were the primary causes across all three countries. Internal impacts were evaluated by accident severity and frequency, while external impacts considered casualties and management priorities. Internal impact results showed mechanical integrity as critical in the U.S., preventive maintenance in the U.K., and human factors in Republic of Korea. For external impacts, human factors were most critical in Republic of Korea. To prioritize safety management elements for chemical accident prevention from an ESG perspective, this study categorized them into three tiers. Tier 1 represents the most critical elements requiring urgent attention, while Tier 3 includes the least critical elements. This tier classification is intended not as an absolute ranking but as a general reference for identifying overall trends in safety management priorities. Tier 1 included the U.K.’s preventive maintenance and human factors across all countries, with Republic of Korea’s human factors being the most vulnerable. Tier 2 revealed operating procedures and human factors as critical, with U.S. emergency preparedness and U.K. design highlighted. Tier 3, with impact scores below 1, was safest. These findings effectively identified safety management priorities to enhance accident prevention. Full article

The water quality of centralized drinking water sources (CDWSs) in the Yangtze River Basin (YRB) has received widespread public attention. Regrettably, due to the lack of large-scale and high-frequency monitoring data, the trends, sources, and risks of heavy metals (HMs) in the water of CDWSs in the YRB are still unclear. In addition, the correlation between HMs and water quality parameters in natural water has not been established, which greatly affects the efficiency of water management. Herein, we collected data for eight HMs and twelve water quality physical–chemical parameters from 114 CDWSs in 71 prefecture-level cities in the YRB region. An unprecedented spatial distribution map of HMs in the YRB region was drawn, and the response of HMs to water quality and nutrient levels was studied. Overall, the level of HM pollution was low, but the threat of chloride, nitrogen, and phosphorus still exists. The detection rates of the eight HMs ranged from 60.00% (Ti) to 99.82% (Fe), and the mean concentrations were ranked as follows: Fe (36.576 ± 36.784 μg/L) > Mn (7.362 ± 7.347 μg/L) > Ti (3.832 ± 6.344 μg/L) > Co (2.283 ± 3.423 μg/L) > Se (0.247 ± 0.116 μg/L) > Cd (0.089 ± 0.286 μg/L) > Be (0.054 ± 0.067 μg/L) > Tl (0.015 ± 0.012 μg/L). In the large geographic area, the total concentrations of the eight HMs exhibited a fluctuating decay trend over time from 2018 to 2022. Geographically, industrial and agricultural production and geological coupling factors led to significant spatial heterogeneity in HM concentrations in the following order: midstream > downstream > upstream. Importantly, this study proved that Cl⁻, SO₄²⁻, nitrogen, and phosphorus may drive the absorption and transfer of HMs in natural water. Fortunately, exposure to the eight HMs does not cause adverse health effects in humans. Full article

Metabolomic data often present challenges due to high dimensionality, collinearity, and variability in metabolite concentrations. Machine learning (ML) application in metabolomic analyses is enabling the extraction of meaningful information from complex data. Bringing together domain-specific knowledge from metabolomics with explainable ML methods can refine the predictive performance and interpretability of models used in atherosclerosis research. In this work, we aimed to identify the most impactful metabolites associated with the presence of atherosclerotic cardiovascular disease (ASCVD) in cross-sectional case–control studies using explainable ML methods integrated with metabolomics domain knowledge. For this, a subset from the FLEMENGHO cohort with metabolomic data available was used as the training cohort, including 63 patients with a history of ASCVD and 52 non-smoking controls matched by age, sex, and body mass index from the same population. First, Partial Least Squares Discriminant Analysis (PLS-DA) was applied for dimensionality reduction. The selected metabolites’ correlations were analyzed by considering their chemical categorization. Then, eXtreme Gradient Boosting (XGBoost) was used to identify metabolites that characterize ASCVD. Next, the selected metabolites were evaluated in an external cohort to determine their effectiveness in distinguishing between cases and controls. A total of 56 metabolites were selected for ASCVD discrimination using PLS-DA. The primary identified metabolites’ superclasses included lipids, organic acids, and organic oxygen compounds. Upon integrating these metabolites with the XGBoost model, the classification yielded a test area under the curve (AUC) of 0.75. SHAP analyses ranked cholesterol, 3-methylhistidine, and glucuronic acid among the most impactful features and showed the diversity of metabolites considered for building the ASCVD discriminator. Also using XGBoost, the selected metabolites achieved an AUC of 0.93 in an independent external validation cohort. In conclusion, the combination of different metabolites has the potential to build classifiers for ASCVD. Integrating metabolite categorization within the SHAP analysis further enhanced the interpretability of the model, offering insights into metabolite-specific contributions to ASCVD risk. Full article

Introduction: Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a major complication following hematopoietic stem cell transplantation, resulting from immune and chemical toxicity in the sinusoidal endothelium and hepatocellular damage. In the most severe cases, multiorgan dysfunction occurs, so it is essential to promptly identify patients at greater risk of SOS/VOD and to adopt prophylactic strategies. Objectives: This study aims to systematize the impact of different approaches as primary prophylaxes against SOS/VOD in patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A systematic review and meta-analysis of randomized clinical trials evaluating different strategies for primary prophylaxis of SOS/VOD was carried out in pairwise fashion and with a consistent network structure. The odds ratio (OR) and corresponding confidence intervals were calculated using the random-effects model. Heterogeneity was assessed by the I² method and the efficacy of each approach was estimated by SUCRA (surface under the cumulative ranking curve). Results: Considering all patients undergoing HSCT, ursodeoxycholic acid (UDCA) [OR = 0.38, 95%CI 0.14–1.06, SUCRA = 0.720] was associated with a lower incidence of VOD while defibrotide reached a modest reduction in its incidence [OR = 0.64, 95%CI 0.23–1.67; SUCRA = 0.486]. Considering the subgroup of patients undergoing hematopoietic progenitors allotransplantation, defibrotide scored higher [OR = 0.51, 95%CI 0.09–2.85, SUCRA = 0.650] by comparison with UDCA [OR = 0.53, 95%CI 0.14–1.96, SUCRA = 0.639]. Conclusions: This is the first meta-analysis comparing primary prophylaxes against SOS/VOD. UDCA yielded more promising results when considering all patients undergoing hematopoietic stem cell transplantation, yet, in a subgroup analysis of the ones exposed to allogeneic grafts, it becomes not significantly overrun by defibrotide. Full article

China’s chemical industry has faced severe environmental, social, and governance (ESG) issues, such as high safety and environmental accidents and risks. To address these issues and promote industrial upgrading, China’s central government has issued a national relocation and improvement policy targeting its chemical industry. However, its countrywide policy implementation may also lead to other ESG risks during the relocation of chemical enterprises, namely industrial transfer. The typical ESG risks that appear to occur in developed eastern region provinces include a one-size-fits-all solution and unemployment, while less developed central and western region provinces may encounter pollution transfer, carbon leakage, environmental injustice, and health disparities. These ESG risks might overlap with other economic and financial (non-ESG) risks, like stranded assets, industry hollowing-out, and debt sustainability issue. These ESG and non-ESG risks could result from potential mismatches between chemical enterprises and chemical parks, categorized as mismatching errors explained by social-ecological systems, behavioral economics, and information economics. To better manage these risks, we propose an ESG matching policy comprising a national standardized ESG scoring and ranking system, a deferred acceptance mechanism, and a score announcement instrument. Such a policy innovation aims at achieving fair and efficient chemical enterprise–chemical park pairs, which would help manage both ESG and non-ESG risks and provide a just transition toolkit for China and other developing countries. Full article

Palytoxins are a group of highly potent and structurally complex marine toxins that rank among some of the most toxic substances known to science. Palytoxins are naturally synthesized by a variety of marine organisms, including Palythoa zoanthids, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria, and are widely distributed in tropical and temperate regions where they can bioaccumulate in marine life. The evolution of research on palytoxins has been an intricate exchange between interdisciplinary fields, drawing insights from chemistry, biology, medicine, and environmental science in efforts to better understand and mitigate the health risks associated with this family of toxins. In this review, we begin with a brief history covering the discovery of this group of toxins and the events that led to its isolation. We then focus on the chemical structure of these compounds and their proposed mechanism of action. Finally, we review in vitro, ex vivo, and in vivo studies related to their toxicity, with the aim to provide a broad overview of the current knowledge on palytoxin toxinology. Full article

Background: Urothelial bladder carcinoma (UBC) is the most frequent histologic form of bladder cancer, constituting 90% of the cases. It is important to know the risk factors of UBC to avoid them and to decrease its recurrence after treatment. The aim of this review was to provide an overview of the risk factors associated with UBC incidence. Methods: A comprehensive literature search from 2012 to 2024 was carried out in databases such as PubMed, Google Scholar, and Medline with potential keywords such as “bladder cancer”, “urothelial bladder cancer”, “incidence of urothelial bladder cancer worldwide”, “mortality rate of bladder cancer”, “incidence according to gender”, “treatment for bladder cancer”, and “risk factors of bladder cancer”. Smoking tobacco was comprehended to be the major risk factor for UBC. Smoke from tobacco products contains polycyclic aromatic hydrocarbons (PAHs) and aromatic amines such as 4-aminobiphenyl, which are known to cause UBC. Smoking-related bladder cancer mortality ranks just second to smoking-related lung cancer mortality. For non-smokers, pollution became a major risk factor associated with UBC. Polycyclic aromatic hydrocarbons (PAHs) are linked to many cancers, especially to UBC. Indoor and outdoor pollution generates VOCs (volatile organic compounds) and PAHs. Small-particle matter < 2.5 is linked to UBC and lung cancers. Drinking chlorinated water is linked to UBC. Also, swimming in chlorinated pools that produce trihalomethanes increases the risk of many cancers, and especially of bladder cancer. Occupational exposure to carcinogens, specifically aromatic amines, is a significant UBC risk factor. It has been estimated that approximately 20% of all UBCs may be linked to this type of exposure, primarily in industrial settings that treat dye, paint, petroleum chemicals, and metal. The other risk factors included genetics, diet, and medical conditions. Alcohol, consumption of processed meat and whole milk, and higher intakes of selenium and vitamins A and E also contribute to the development of UBC. Further, chemotherapeutic agents, oral hypoglycemic drugs, and radiation therapy are positively associated with UBC. Conclusions: The significance of the initial prevention of UBC must be emphasized, and especially programs for quitting cigarettes should be encouraged and supported. However, smoking is not the only risk factor for UBC. For non-smokers, other risk factors should be investigated. Air and water pollution are linked to UBC. Indoor and outdoor pollution should be more controlled. Patients and people should be informed of the risk of drinking chlorinated water and swimming in chlorinated pools. Full article

The in vitro biotransformation of phenol at 11 °C was studied using pre-spawn adult rainbow (Oncorhynchus mykiss) (RBT), brook (Salvelinus fontinalis) (BKT), and lake trout (Salvelinus namaycush) (LKT) hepatic microsomal preparations. The incubations were optimized for time, cofactor concentration, pH, and microsomal protein concentration. Formation of Phase I ring-hydroxylation and Phase II glucuronidation metabolites was quantified using HPLC with dual-channel electrochemical and UV detection. The biotransformation of phenol over a range of substrate concentrations (1 to 180 mM) was quantified, and the Michaelis–Menten kinetics constants, Km and Vmax, for the formation of hydroquinone (HQ), catechol (CAT), and phenylglucuronide (PG) were calculated. Species differences were noted in the Km values for Phase I enzyme production of HQ and CAT, with the following rank order of apparent enzyme affinity for substrate: RBT > BKT = LKT. However, no apparent differences in the Km for Phase II metabolism of phenol to PG were detected. Conversely, while there were no apparent differences in Vmax between species for HQ or CAT formation, the apparent maximum capacity for PG formation was significantly less in LKT than that observed for RBT and BKT. These experiments provide a means to quantify metabolic activation and deactivation of xenobiotics in fish, to compare activation and deactivation reactions across species, and to act as a guide for future predictions of new chemical biotransformation pathways and rates in fish. These experiments provided the necessary rate and capacity (Km and Vmax) inputs that are required to parameterize a fish physiologically based toxicokinetic (PB-TK) model for a reactive chemical that is readily biotransformed, such as phenol. In the future, an extensive database of these rate and capacity parameters on important fish species for selected chemical structures will be needed to allow the effective use of predictive models for reactive, biotransformation chemicals in aquatic toxicology and environmental risk assessment. Full article

Population exposure to endocrine disrupting chemical- bisphenols, which are used commonly in food containers and drinking water pipes in Europe, is above acceptable health and safety levels, according to updated research data. In order to evaluate the most abundant potential migrants in canned sweetened beverages marketed in Poland, we performed the HPLC-MS screening test of the migrants present in the can coating material. The analyzed samples represented the three top-ranked companies of the global soft drink market; it is reasonable to assume that the obtained data are of global validity. The tested can coatings and beverages contained bisphenols conjugates such as five butoxyethanol (BuOEtOH) adducts with bisphenol A diglycidyl ether (BADGE), one butoxyethanol adduct with bisphenol A monoglycidyl ether (BAMGE), and cyclo-di-BADGE. The performed HPLC-MS/MS analysis in the MRM mode enabled evaluation of the concentrations of the detected conjugates in canned beverages which were found to be very low, namely at the level of 1 µg/L. On the other hand, the high consumption of canned beverages may yield a risk associated with the presence of these compounds in the diet. The subsequent HPLC-QTOF-MS/MS experiments allowed, for the first time, a detailed determination of the fragmentation pathways of the detected migrants as well as detection of the isomers of the two migrants, namely BADGE + BuOEtOH and BADGE + BuOEtOH + HCl. Full article

Soil contamination with potentially toxic elements (PTEs) in the Malwa region belt of Punjab, India, can be a serious concern as a result of intensive agricultural practices and overuse of agrochemicals. The main objectives of the present study were to evaluate the spatial distribution, geochemical signature, and contamination level/health risk of PTEs in 76 soil samples (0–10 cm) collected from the three districts viz. Muktar, Faridkot, and Moga of Punjab, India. The result shows that PTEs concentrations vary widely in the region, with Fe and Mn distribution patterns being mostly coherent with each other. When compared to the Indian natural soil background values, the average concentration of Pb and Zn were higher than the limit, only Pb exceeded the average values of the world background and upper continental crust (UCC). Spatial autocorrelation plotted with a local indicator of spatial association (LISA) in GeoDa software version 1.18 was used to identify hotspots. A positive spatial autocorrelation (>0.2) was indicated with Moran’s I values for Pb, V, Mn, Cu, and Cr, being highest for Pb. A principal component analysis (PCA) identified the major geo-chemical patterns of Fe-Al-V-Cr and TOC-Mn-Zn-HCO₃⁻, which were positively loaded on PC1. This indicates that Fe/Al-oxyhydroxides and organic matter play a dominant role in controlling metal mobility in soils. This can be further substantiated with the Spearman’s rank correlation values. The contamination factor (CF) indicates that only Pb and Zn (15.7% and 3.9% samples, respectively) were under high risk. This could be due to the excessive application of chemical fertilizers. The large range of degree of contamination (C_deg) values suggests that there are variations in the degree of soil pollution due to PTEs. A little over 3.9% of samples had significant contamination, compared to 72.3% of samples with low contamination and 23.6% of samples with moderate contamination. Human non-carcinogenic and carcinogenic risk levels were investigated. The hazard index (HI) values for adult ranged from 0.00 to 0.2, and values for children ranged from 0.009 to 1.2. These findings suggest that both children and adults are not at potential risk, except in a few locations. Overall, the results of this study provide the current baseline status of toxic elements in agricultural soil. This would be helpful for developing strategies for sustainable management of the soil resources in the region, as well as for future monitoring programs of the soil quality in the Malwa region as a whole, to track any changes in the contamination levels over time. Full article

To explore the contamination status and identify the source of the heavy metals in the sediments in the major inflow rivers of Dianchi Lake in China, sediment samples were collected and analyzed. Specifically, the distribution, source, water quality, and health risk assessment of the heavy metals were analyzed using correlation analysis (CA), principal component analysis (PCA), the heavy metal contamination factor (C_f), the pollution load index (PLI), and the potential ecological risk index (PERI). Additionally, the chemical fractions were analyzed for mobility characteristics. The results indicate that the average concentration of the heavy metals in the sediment ranked in the descending order of Zn > Cr > Cu > Pb > As > Ni > Cd > Hg, and most of the elements existed in less-mobile forms. The C_fwas in the order of Hg > Zn > Cd > As > Pb > Cr > Ni; the accumulation of Hg, Zn, Cd, and As was obvious. Although the spatial variability of the heavy metal contents was pronounced, the synthetical evaluation index of the PLI and PERI both reached a high pollution level. The PCA and CA results indicate that industrial, transportation, and agricultural emissions were the dominant factors causing heavy metal pollution. These results provide important data for improving water resource management efficiency and heavy metal pollution prevention in Dianchi Lake. Full article

Arsenic (As) contamination is a serious global concern, polluting our natural resources, including water and soil, and posing a danger to the environment and public health. Arsenic is present in the groundwater of several countries and this contaminated water is used for irrigation, drinking, and food preparation, which poses the greatest threat to public health. Nearly 106 countries are affected by groundwater arsenic contamination and an estimated 230 million individuals worldwide are exposed to its adverse health effects, including increased cancer risks, associated cardiovascular disease and diabetes, skin lesions, neurological effects, kidney damage, and foetal or cognitive-development-related complications. Arsenic is highly toxic and ranked first in the priority list of ATSDR (Agency for Toxic Substances and Disease Registry, 2022) and among the 10 chemicals of major public health concern on the World Health Organization (WHO) list. The maximum permissible level of arsenic in drinking water has been established at 10 µg/L by WHO, as well as by the Environmental Protection Agency (EPA) and European Union (EU). These regulatory standards underscore the gravity of the problem, and actions to prioritise the development of effective detection, mitigation strategies, and collaborative initiatives are necessary. This opinion article covers (i) arsenic footprints—global scenario and impact, (ii) awareness and education and (iii) mitigation approaches (detection and removal strategies) and future perspectives, which collectively will help in controlling and preventing As contamination of our global water resources. Regulatory and legislative bodies and development agencies are crucial for raising awareness and countering this alarming concern by implementing collaborative actions to protect our environment and public health and to provide safe drinking water for all. Full article