Search Results (178)

Cyclophosphamide (CYP) is an effective chemotherapeutic, but its use is limited by hemorrhagic cystitis caused by its toxic metabolite acrolein. Acrolein, when concentrated in the urine, triggers oxidative stress, leading to urothelial inflammation and cell death. Given that albumin is the most abundant plasma protein that contains free thiol groups capable of neutralizing electrophiles and oxidants, we, therefore, hypothesized that albumin could mitigate CYP-induced bladder injury. Here, we tested this hypothesis. In CYP-induced mouse cystitis, albumin administration markedly reduced bladder enlargement, edema, and hemorrhage, effectively normalizing the bladder weight. Albumin also reduced bladder oxidative injury and preserved the expression of anti-ferroptotic proteins, including the cystine/glutamate antiporter xCT and glutathione peroxidase 4 (GPX4). In addition, albumin-treated mice showed less leakage of inflammatory protein into bladder tissue. In vitro, albumin protected urothelial cells from acrolein-induced cell death. It also significantly prevented H₂O₂-induced cytotoxicity. Mechanistically, albumin acted as an extracellular scavenger that preferentially reacted with acrolein and H₂O₂, thereby sparing cellular components from oxidative damage. Notably, oral albumin supplementation similarly attenuated CYP-induced cystitis. Furthermore, albumin administration improved survival in a high-dose CYP toxicity model. These findings establish albumin as a potent protector against CYP-induced toxicity by sequestering acrolein and scavenging reactive oxygen species. Albumin supplementation could be a practical strategy to mitigate chemotherapy-associated bladder and systemic injury. Full article

The oxidation of flexible polyurethane (PUR) foams significantly impacts product durability, vehicle indoor air quality, and volatile organic compound (VOC) emissions. This study investigates oxidation kinetics and VOC emissions (65–155 °C) from foams with indices between 70 and 115 (molar ratio of NCO to NCO-reactive groups × 100), where a higher index represents greater hard segment (methylene diphenyl diisocyanate) and lower soft segment (polyether polyol) content. Using a flow-through setup with PTFE chambers and Tenax thermodesorption tubes and dinitrophenylhydrazine (DNPH) cartridges, VOCs from initial analyte loading, hydroperoxide degradation, and autoxidation were distinguished, providing robust kinetic data unaffected by diffusion interference. A higher index accelerated soft segment degradation, increasing oxidation rates and VOC emissions. The activation energy of 1,2-propanediol-1-acetate-2-formate increased from 87 kJ/mol in low-index to 108 kJ/mol in high-index formulations. VOC emissions from high-index foams were tripled for acetaldehyde during long-term aging at 65 °C. While most emissions followed Arrhenius behavior, formaldehyde and acrolein deviated above 100 °C, with higher hard-segment content extending their Arrhenius range. These findings link PUR composition to degradation behavior and emissions, enabling formulation improvements. The results advance methods for evaluating raw material contributions and the performance of antioxidants under realistic aging conditions. Full article

Thermal oxidation of edible oils during high-temperature cooking produces complex fumes containing harmful volatile compounds. However, the role of water, a common co-reactant in practical cooking, remains insufficiently understood. In this study, oleic acid was used as a model compound to investigate thermal oxidation. Online monitoring using synchrotron radiation photoionization mass spectrometry (SR-PIMS) revealed that water significantly increased the emission of volatile acetaldehyde and acrolein, with maximum increases of 164% and 123% at 10% water addition. Complementary offline GC-MS analysis showed enhanced formation of (E)-2-decenal, (E,E)-2,4-decadienal, and (E)-2-undecenal, suggesting these unsaturated aldehydes may be key intermediates. Mechanistically, oleic acid underwent free radical-mediated peroxidation to form (E)-2-decenal, (E)-2-undecenal, and (E,E)-2,4-decadienal. These intermediates subsequently decomposed into acetaldehyde and acrolein via hydration, retro-aldol condensation, and hydroperoxide scission, with water accelerating both processes. Overall, these findings highlight water’s critical role in promoting the generation of harmful volatile aldehydes in oil fumes. Full article

The conversion of alkanes/alkenes into useful intermediates is highly important in the chemical industry. In this study, the physicochemical properties and catalytically active forms of bismuth molybdates (BiMo) were investigated using the selective oxidation of propene to acrolein as a model reaction. The catalysts were prepared by two methods, coprecipitation and spray-drying, with emphasis on spray-drying. The catalysts were characterized using X-ray diffraction, N₂ adsorption/desorption isotherms, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The catalytic properties of the BiMo samples were studied in a conventional fixed-bed reactor operated under different reaction conditions. The one-dimensional (1D) pseudohomogeneous model was applied to describe the obtained experimental results. The experimental kinetic data were correlated with two complex kinetic models based on multiple reactions (parallel and serial reaction systems). The proposed models were verified by comparing computer simulation data with experimental laboratory results. This study aimed to extend the understanding of the relationship between catalyst composition/structure and catalyst activity/selectivity for different BiMo structures, and to propose kinetic models using two approaches based on parallel and series reactions, in line with efforts to improve the valorization of light olefins. Full article

Acrolein, a highly reactive environmental toxicant widely present in urban air and tobacco smoke, has been implicated in the development of multiple malignancies. In oral tissues, chronic acrolein exposure induces oxidative stress, inflammation, and genetic mutations, all of which are closely linked to the development of oral squamous cell carcinoma (OSCC). Although accumulating evidence indicates a strong association between acrolein exposure and OSCC, its prognostic significance remains poorly understood. In this study, we analyzed transcriptome data to identify differentially expressed genes (DEGs) between tumor and adjacent normal tissues, and screened acrolein-related candidates by intersecting DEGs with previously identified acrolein-associated gene sets. Functional alterations of these genes were assessed using Gene Set Variation Analysis (GSVA), and a protein–protein interaction (PPI) network was constructed to identify key regulatory genes. A prognostic model was developed using Support Vector Machine–Recursive Feature Elimination (SVM-RFE) combined with LASSO-Cox regression and validated in an independent external cohort. Among the acrolein-related DEGs, four key genes (PLK1, AURKA, CTLA4, and PPARG) were ultimately selected for model construction. Kaplan–Meier analysis showed significantly worse overall survival in the high-risk group (p < 0.0001). Receiver operating characteristic (ROC) curve analysis further confirmed the strong predictive performance of the model, with area under the curve (AUC) values of 0.72 at 1 year, 0.72 at 3 years, and 0.75 at 5 years. Furthermore, the high risk score was significantly correlated with a ‘cold’ immune microenviroment, suggesting that acrolein-related genes may modulate the tumor immune microenvironment. Collectively, these findings highlight the role of acrolein in OSCC progression, suggesting the importance of reducing acrolein exposure for cancer prevention and public health, and call for increased attention to the relationship between environmental toxicants and disease initiation, providing a scientific basis for public health interventions and cancer prevention strategies. Full article

This study aimed to determine carbonyl compound concentrations and assess their potential health risk in indoor air at three homes in different areas of the Mexico City Metropolitan Area (MCMA) during the COVID-19 lockdown. Sampling was conducted from March to April 2021, during the home office confinement period. Average concentrations of formaldehyde, acetaldehyde, acrolein, acetone, propionaldehyde, and butyraldehyde in living rooms ranged from 84.15 to 74.93 μg m⁻³, 66.49 to 50.20 μg m⁻³, 60.01 to 41.35 μg m⁻³, 74.58 to 63.02 μg m⁻³, 10.90 to 6.21 μg m⁻³, and 12.45 to 9.91 μg m⁻³, respectively. In bedrooms, concentrations ranged from 84.76 to 59.70 μg m⁻³, 50.12 to 51.73 μg m⁻³, 59.74 to 37.25 μg m⁻³, 76.62 to 59.72 μg m⁻³, 14.45 to 8.40 μg m⁻³, and 10.72 to 8.82 μg m⁻³, respectively. All measured carbonyls had significant indoor concentrations, exceeding those reported in other studies worldwide. From the statistical analysis, it was found that there were significant differences in carbonyl levels between the studied homes. This suggests diverse and prevalent sources in these environments. E-cigarette vapors clearly increased acrolein levels, and the use of personal care and household products (PCHPs) also contributed to higher carbonyl concentrations indoors. The lifetime cancer risk coefficient (LTCR) and hazard quotient (HQ) values for formaldehyde and acetaldehyde exceeded WHO and US EPA recommendations, indicating increased risks of both carcinogenic and non-carcinogenic effects. Full article

Acrolein, a ubiquitous environmental pollutant, is also formed endogenously as a metabolite under oxidative stress conditions. Its adduct to cytosine, 3,N⁴-α-hydroxypropanocytosine (HPC), has recently been shown to be an in vitro substrate for the AlkB dioxygenase. Using a set of indicator plasmids modified with acrolein, we provide evidence that HPC is a mutagenic non-instructional lesion that predominantly induces C→A transversion, and to a lesser extent C→T and C→G base substitutions. HPC is efficiently repaired in vivo by AlkB, even without induction of the adaptive response. However, the mutation frequency did not differ between the wild-type and AlkA-deficient strains, and AlkA glycosylase fails to excise in vitro the acrolein-modified cytosine from the T₂₂(HPC)₃ oligodeoxynucleotide, both indicating that HPC is not a substrate for AlkA. Based on molecular modeling, we further examined the potential differences in the hydrolytic suspensibility of a known AlkA substrate, the acrolein adduct to adenine (HPA), and the cytosine adduct (HPC) at the glycosylase active site. Analysis of both structural and electrochemical properties indicates that, despite an identical type of modification within an equivalent chemical context, including comparable geometry and topology, the glycosidic bond in HPC is considerably less susceptible to hydrolysis than that in HPA. Full article

This paper does not describe the results of a systematic search for the mechanism of action of cyclophosphamide and the consequences and possible indications arising from this mechanism. Rather, it describes a puzzle in which our own results, with some of them being very old, were re-evaluated with the latest biochemical knowledge and supplemented by results from the scientific literature. The mechanism of action of cyclophosphamide, which has been indispensable in clinical practice for 60 years, was unknown until recently simply because biochemical knowledge was lacking and because results from in vitro experiments were uncritically extrapolated to in vivo conditions. In vitro, the DNA alkylating metabolite phosphoramide mustard (PAM) is formed from the CP metabolite aldophosphamide (ALD) by phosphate and bicarbonate ion-catalyzed β-elimination of acrolein; in vivo, however, ALD is cleaved by phosphoesterases or DNA polymerase δ and ε, which are associated with 3′-5′ exonucleases, into the complementary metabolites PAM and 3-hydroxypropanal (HPA). The following describes the mechanism of action of CP, namely the complementary interaction of alkylating PAM and apoptosis-enhancing HPA, and it is shown that by optimizing the complementary effects of PAM and HPA, the antitumor efficacy in the P388 mouse tumor model can be increased by more than ten thousand-fold. Further experiments show that by optimizing the interaction of DNA alkylation and enhancing the resulting apoptosis by HPA, the formation of resistant metastases can be prevented and low-toxicity chemotherapy can be achieved. Full article

The maintenance of intracellular redox homeostasis depends on the GSH/GSSG pair, which is the primary intracellular redox buffer. However, the NADPH/NADP⁺ pair also plays a vital role in this process. The primary source of NADPH is the pentose phosphate pathway and deficiency in the enzymes responsible for NADPH production in this pathway leads to developing of alternative NADPH supply strategies. The choice of compensation strategy has several consequences for cells physiology. The present study investigates how Saccharomyces cerevisiae yeast strains defective in generating NADPH via the pentose phosphate pathway due to deletion of ZWF1, GND1, or GND2 genes, respond to redox homeostasis disruption caused by allyl alcohol, a metabolic precursor of acrolein. Acrolein is a highly reactive aldehyde that rapidly depletes glutathione and triggers oxidative stress. Therefore, cells respond to acrolein through attempts to increase glutathione synthesis, but also by increasing NADPH production. The response requires coordinated action of glutathione- and NADPH-dependent systems. The high sensitivity of the Δgnd1 strain, which is unable to activate an adequate stress response, is evidence of this. The strategy employed by this strain to maintain redox homeostasis is inadequate and may even exacerbate allyl alcohol toxicity. Full article

The physicochemical processes that occur during selective transfer in the contact area of a bronze/steel friction pair lubricated with glycerin are experimentally studied by the polarization method to observe how they influence the tribological properties (friction and wear) of the pair. The proposed method allows for the study of tribochemical transformations of glycerin and the friction pair materials during the work process with selective transfer. The analysis of the experimental results allows for the establishment of the conditions for a stable and stationary selective transfer during the operation of the bronze/steel pair, by friction, at which the friction coefficient (COF) values and wear are low. This was achieved by implementing continuous lubrication with fresh glycerin in the contact area, choosing the optimal flow rate, and maintaining an optimal ratio between glycerin and the chemical transformation products, within well-established limits, to avoid undesirable consequences. Acrolein, as a product of chemical transformation (resulting from the catalytic dehydration of glycerin), is the most important for the initiation and stability of the selective transfer, and as the main reaction product, also represents a pathway of regeneration. Thus, it was found that the friction relative moments and the acrolein concentration presented conclusive/specific results at loads of 4–15 MPa and a sliding speed of 0.3 m/s. The optimum lubricant entry speed is 15–30 mg/min, for a minimum COF and reduced wear (about 0.028–0.03 at relatively high operating temperatures (45 and 60 °C)), and at low temperatures (30 °C) the minimum COF is about 0.038, but the lubricant inlet entry speed increases considerably, by around 1000 mg/min. Therefore, this paper aims to demonstrate the possibility of moving to another stage of practical use of a friction pair (with greatly improved tribological properties) that operates with selective transfer, much different from the ones still present, using a lubricant with special properties (glycerin). The research method used (polarization) highlights the physicochemical properties, tribochemical transformations of the lubricant, and the friction pair materials present in the contact area, for the understanding, maintenance, and stability of selective transfer, based on experiments, as a novelty compared to other studies. Full article

Saffron, branded as Repron^®, is effective in slowing the progression of several neurodegenerative diseases. Its production, however, requires specific cultivation techniques and procedures that, together with low yields, make it expensive. To address this challenge, hydroponic cultivation has been adopted. Previous studies have shown that hydroponically cultivated saffron and Repron^® share comparable chemical compositions and neuroprotective effects under oxidative stress conditions. In this study, we evaluated the protective properties of extracts derived from Crocus sativus L. waste, compared with those of saffron derived from stigmas. Human retinal pigment epithelium (ARPE-19) cells were pre-treated with extracts of various plant waste fractions before being subjected to three stress conditions: H₂O₂-induced oxidative stress (500 μM, 3 h), lipopolysaccharide (LPS; 0.25 mg/mL, 24 h), and hyperglycemia (25 mM glucose, 96 h). Saffron Repron^® served as a positive control. The results revealed that the extract derived from C. sativus waste had superior protective effects against oxidative stress and inflammation by preserving the state of the mitochondria and tight junctions (ZO-1); conversely, the tepal extract alone was more effective under hyperglycemic conditions by also modulating acrolein levels. These results suggest that different plant fractions contain bioactive compounds with specific protective actions, which together lead to increased cell survival. Full article

The development of polymer binders with tailored functionalities and green manufacturing processes is highly needed for high-performance lithium–sulfur batteries. In this study, a readily hydrolyzable 3,9-divinyl-2,4,8,10-tetraoxaspiro-[5.5]-undecane is utilized to prepare a water-based binder. Specifically, the acrolein produced by hydrolysis undergoes in situ polymerization to form a linear polymer, while the other hydrolyzed product, pentaerythritol, physically crosslinks these polymer chains via hydrogen bonding, generating a network polymer (BTU). Additionally, gallic acid (GA), a substance derived from waste wood, is further introduced into BTU during slurry preparation, forming a biphenol-containing binder (BG) with a multi-hydrogen-bonded structure. This resilience and robust cathode framework effectively accommodate volumetric changes during cycling while maintaining efficient ion and electron transport pathways. Furthermore, the abundant polar groups in BG enable strong polysulfide adsorption. As a result, sulfur cathode with a high mass loading of 5.3 mg cm⁻² employing the BG (7:3) binder still retains an areal capacity of 4.7 mA h cm⁻² after 50 cycles at 0.1 C. This work presents a sustainable strategy for battery manufacturing by integrating renewable biomass-derived materials and eco-friendly aqueous processing to develop polymer binders, offering a green pathway to high-performance lithium–sulfur batteries. Full article

Environmental pollution significantly exacerbates various diseases, particularly those affecting the cardiovascular and respiratory systems. Our previous studies have shown that acrolein, an environmental pollutant, promotes atherosclerosis by downregulating the circadian clock genes (CLOCK/BMAL1) and disrupting circadian rhythm. We have also found that intermittent fasting (IF), closely linked to the circadian clock, may mitigate atherosclerosis induced by acrolein. Ferroptosis, a newly identified form of regulated cell death, is associated with the acceleration of atherosclerotic development, but its relationship with the circadian clock is not well understood. In this study, we explored the potential of IF to alleviate ferroptosis by modulating the circadian clock. Our in vivo experiments revealed that IF reversed ferroptosis and upregulated CLOCK/BMAL1 in APOE-/- mice. In human umbilical vein endothelial cells (HUVECs), we discovered that acrolein-induced ferroptosis leads to cell death, while short-term starvation (STS, IF cell model) reversed this effect. Acrolein also suppressed the expression of AMP-activated protein kinase (AMPK), nuclear factor erythroid 2-related factor 2 (NRF2), and CLOCK/BMAL1, which were restored by subsequent STS treatments. Additionally, the overexpression of CLOCK/BMAL1 mitigated ferroptosis, consistent with findings from CLOCK gene knockout experiments. Notably, CLOCK/BMAL1 and AMPK/NRF2 were found to be mutually regulated. Concurrently, the AMPK and NRF2 signaling pathways may be interdependent and act in concert. In conclusion, our findings suggest that IF modulates the CLOCK/BMAL1-AMPK/NRF2 pathway to alleviate acrolein-induced ferroptosis, offering a potential strategy to address health issues related to environmental pollution. Full article

A body of evidence indicates an association between ultraprocessed foods (UPFs) and health outcomes. Most of it has been obtained through preclinical studies, although a number of observational studies substantiate how a high intake of these products increases the risk of neuropsychiatric disorders, and an increasing amount of dietary intervention studies confirm these findings. The aim of this narrative review is to describe some of the putative mechanisms involved in the deleterious effects of a high intake of UPFs on neuropsychiatric outcomes. A myriad of unhealthy actions may be associated with the consumption of UPFs, and some mechanisms are being discussed. They include UPFs’ high caloric density; their high sugar, sodium, and additives content and low amounts of fiber; and a high palatability that induces overconsumption, acting as obesogens. Moreover, thermal treatment of these foods generates oxidative products such as glycotoxins, lipotoxins, and acrolein, all of which affect the brain. The chemical products act, directly or indirectly, on the gut microbiome and affect the gut–brain axis, causing neuroinflammation, oxidative stress, and neurodegeneration. UPFs also exert various epigenetic effects that affect mental health and might explain the intergenerational inheritance of neuropsychiatric disorders. A diet containing a high proportion of these foods has a low nutritional density, including bioactive protective agents such as antioxidant and anti-inflammatory compounds that promote eubiosis. The evidence shows that UPFs intake affects neuropsychiatric outcomes such as neurodegeneration, cognitive decline, dementia, and mood disorders and reinforces the need to promote a healthy dietary pattern throughout all life stages, thus interfering with the current commercial determinants of health. Full article

Ozone (O₃) is a crucial atmospheric component that significantly affects air quality and poses considerable health risks to humans. In the coastal areas of the Yangtze River Delta, typhoons, influenced by the subtropical high-pressure system, can lead to complex ozone pollution situations. This study aimed to explore the causes, sources, and health risks of O₃ pollution during such events. Ground-based data from Jiaxing City’s key ozone precursor (VOCs) composition observations, ERA5 reanalysis data, and models CMAQ-ISAM and PMF were employed. Focusing on the severe ozone pollution event in Jiaxing from 3 to 11 September 2022, the results showed that local ozone production was the main contributor (60.8–81.4%, with an average of 72.3%), while external regional transport was secondary. Concentrations of olefins and aromatic hydrocarbons increased remarkably, playing a vital role in ozone formation. Meteorological conditions, such as reduced cloud cover during typhoon periphery transit, promoted ozone accumulation. By considering the unique respiratory exposure habits of the Chinese population, refined health risk assessments were conducted. Acrolein was found to be the main cause of chronic non-carcinogenic risks (NCRs), with NCR values reaching 1.74 and 2.02 during and after pollution. In lifetime carcinogenic risk (LCR) assessment, the mid-pollution LCR was 1.73 times higher, mainly due to 1,2-dichloroethane and benzene. This study presents a methodology that is readily adaptable to analogous pollution incidents, thereby providing a pragmatic framework to guide actionable local government policy-making aimed at safeguarding public health and mitigating urban ozone pollution. Full article