Search Results (228)

Mediterranean meadows of Posidonia oceanica are chronically exposed to complex mixtures of environmental contaminants, including metals and trace elements derived from coastal urbanization, maritime traffic, and industrial activities. This study aimed to assess metal-related toxicity in P. oceanica by integrating multi-element burden analysis with a panel of oxidative stress biomarkers. Concentrations of a wide suite of elements were quantified in samples of internal (juvenile), intermediate, and external (adult) leaves, reflecting the ontogenetic structure of the plant. Oxidative responses were evaluated using five biomarkers [i.e., hydrogen peroxide (H₂O₂), lipid peroxidation (TBARS), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT)] measured on each leaf compartment. Biomarker data were standardized and integrated into a merged Stress Index summarizing overall physiological toxicity. Associations between individual elements, the sum of all measured elements (ΣallElements), the Stress Index, and single biomarkers were explored using Pearson correlation analysis. Juvenile leaves exhibited the highest Stress Index values, elevated H₂O₂ and TBARS, and marked activation of SOD and GST, indicating early oxidative toxicity. Intermediate leaves showed a trend toward increased CAT activity, not reaching statistical significance, along with minimal damage, suggesting effective detoxification, whereas adult leaves accumulated higher levels of Fe, Ni, and Pb, but displayed moderate stress responses. Overall, leaf-class structure strongly modulated both exposure and toxicological response. The integration of ΣAllElements with multi-biomarker indices provides a robust framework for diagnosing metal-related toxicity in P. oceanica under realistic multi-element exposure scenarios. Full article

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) remains a high-risk entity despite advances in tyrosine kinase inhibitors (TKIs), immunotherapy, and cellular therapies. Relapse driven by clonal evolution, central nervous system (CNS) sanctuary disease, and TKI resistance, particularly T315I mutations, continues to limit durable disease control. Asciminib, a first-in-class allosteric BCR::ABL1 (STAMP) inhibitor, has demonstrated efficacy and favorable tolerability in chronic myeloid leukemia, but its optimal role in Ph+ ALL remains to be defined. We report a three-patient case series of Ph+ acute leukemia treated with asciminib across diverse high-risk clinical settings, including multiply relapsed disease, CNS involvement, T315I-mutated leukemia, post-CAR-T-cell relapses, and transplant bridging. Clinical outcomes are contextualized through a comprehensive review of emerging clinical trial data, real-world cohorts, and mechanistic studies evaluating asciminib in Ph+ ALL. Across all cases, asciminib was incorporated as part of combination or consolidation strategies rather than as monotherapy in active disease. Asciminib contributed to molecular disease control, CNS leukemia clearance, and successful bridging to allogeneic transplantation or cellular therapy, with acceptable tolerability and no major vascular toxicity. Integration of published evidence demonstrates that asciminib exhibits consistent biological activity in Ph+ ALL, with improved durability when used in rational combinations, particularly with immunotherapy or ATP-competitive TKIs. Preclinical data further support asciminib’s compatibility with antibody-based and cellular therapies through preservation of immune effector function. Asciminib represents a versatile but context-dependent therapeutic option in Ph+ ALL. Its greatest clinical value appears to lie in rational combination regimens, maintenance strategies, and bridging to definitive therapies rather than single-agent salvage. Emerging structural biomarkers and ongoing clinical trials are expected to further refine patient selection, sequencing, and optimal integration of asciminib, particularly in CNS-involved disease and post-CAR-T cell relapse. Full article

Cowpeas are a legume widely consumed in Brazil. Given this, the objective of this study was to investigate the presence of metals (loids) in pods and leaves of Vigna unguiculata located near a highway with high vehicle traffic and a landfill, and to assess possible risks to human health. Pod and leaf samples were collected at nine points between the highway and the landfill. The elements were analyzed by inductively coupled plasma optical emission spectroscopy (ICP-OES) and quantified. The risk to human health was assessed using risk quotient and risk index values. A quantitative analysis of the chemical elements was also performed using the maximum tolerable intake level. Element concentrations were higher in the leaves than in the pods. The human health risk analysis showed that the average daily consumption of both pods (44 g/day) and leaves (67 g/day) may pose a chronic health risk to adult men and women, due to simultaneous exposure to multiple metals. It was concluded that the plant is contaminated and that its ingestion can cause toxicity, warranting warnings against cultivating areas near anthropogenic activities that may be contaminated with heavy metals, thereby affecting nutritional safety. Full article

The effects of static magnetic field (SMF) treatment on the solid-state culture of Sanghuangporus vaninii (SV) were investigated to enhance metabolite production and bioactivity. SMF parameters including intensity, exposure duration, and temperature were optimized, and treatment at 4 mT for 2 h per day produced the most pronounced effects, increasing total flavonoid (TFC), polyphenol (TPC), and triterpenoid (TTC) contents by 61–438% compared with the control. Ultrasonic extraction and semi-preparative chromatography enabled the isolation of three key compounds: D-(+)-trehalose (1), 5,7-dihydroxy-3,4′-dimethoxyflavone (2), and pinolenic acid (3), all of which were elevated following SMF treatment. Importantly, SMF exposure was associated with enhanced inhibitory activities against enzymes relevant to chronic metabolic disorders. The overall inhibitory activities against α-amylase, α-glucosidase, pancreatic lipase, and xanthine oxidase increased by 6–28% compared with the control, reaching a maximum inhibition of 97.60 ± 0.17%. Preliminary in vitro screening at 100 μg/mL showed that compounds 1 and 2 inhibited both α-amylase and α-glucosidase, whereas compound 3 selectively inhibited pancreatic lipase. Subsequent IC₅₀ analysis confirmed that compound 2 under SMF treatment exhibited inhibitory activity comparable to acarbose against α-amylase (45.62 μg/mL vs. 52.18 μg/mL) and α-glucosidase (38.74 μg/mL vs. 35.42 μg/mL). In addition, compound 3 showed moderate inhibition of pancreatic lipase with an IC₅₀ value of 42.15 μg/mL. These findings suggest that SMF treatment may enhance metabolite production and in vitro enzyme inhibitory activity in S. vaninii. However, these results are limited to in vitro assays, and further studies including cellular and in vivo validation, toxicity assessment, and pharmacokinetic evaluation, are required before any therapeutic or industrial applications can be considered. Full article

Background: Hyperuricemia (HUA) is a metabolic disorder that severely threatens human health. Chronic uric acid (UA) overload promotes the progression of tubulointerstitial fibrosis (TIF), leading to impaired UA excretion. Our previous studies identified HIPK2 inhibitor XRF-1021, which exhibits robust anti-TIF activity and lowers UA levels in vivo. This study aimed to elucidate its UA-lowering mechanism and therapeutic potential for HUA. Methods: Uricase and xanthine oxidase (XOD) assays were performed to assess effects on UA degradation/production. HEK293T cells transiently expressing UA transporters and gene-knockdown rats were used to evaluate transporter inhibition, while HK-2 cells were analyzed by Western blot. Pharmacokinetics were characterized in rats. Efficacy was tested in potassium oxonate-induced acute HUA rats, diet/adenine-induced chronic HUA quails, and adenine-induced mice with HUA secondary to TIF. Maximum tolerated dose and long-term toxicity were assessed in rats. Results: XRF-1021 neither activated uricase nor inhibited XOD, indicating no direct effect on UA catabolism or synthesis. Instead, XRF-1021 inhibited URAT1 and GLUT9, reducing renal UA reabsorption, while sparing OAT3, OAT4, and ABCG2 activity and upregulating OAT3 and NPT4, suggesting minimal risk of disrupting drug or uremic toxin handling. XRF-1021 showed dose-dependent systemic exposure in rats, lowered serum UA, and provided renal protection in vivo. LD₅₀ values were 2345.4 mg/kg (male) and 1078.9 mg/kg (female), with no obvious toxicity after long-term dosing. Conclusions: XRF-1021 lowers UA by inhibiting URAT1 and GLUT9 to enhance renal UA excretion and provides kidney protection, supporting XRF-1021 as a promising candidate for HUA therapy. Full article

Honey is consumed worldwide for its nutritional and medicinal value, but it can also expose people to toxic metals from environmental contamination. This study analyzes heavy metal levels and assesses health risks using inductively coupled plasma optical emission spectrometry (ICP-OES) in honey collected from three areas in the Kellem Wollega Zone, Ethiopia: Dambi Dollo, Gawo Kebe, and Anafilo. The concentrations followed the order: Zn > Fe > Pb > Mn > Cu > Ni > Cd. Notably, Pb and Cd levels exceeded the WHO/FAO maximum permissible limits. The assessment of non-carcinogenic health risks for adult consumers based on the average daily dose, target hazard quotient, and hazard index indicated that all calculated values were below the critical threshold of 1. This result suggests that honey consumption poses no significant non-carcinogenic risk. In contrast, the estimated target cancer risk and cumulative cancer risk (∑TCR) exceeded safety thresholds, indicating potential moderate lifetime carcinogenic risk from chronic exposure. Likely sources of high metal levels include local mining activities, agricultural inputs, and improper honey storage. Consequently, these findings highlight the need for continuous environmental monitoring, stricter regulations, and improved apicultural practices to ensure honey safety and protect public health. Full article

Background/Objectives: Mucuna pruriens (Linn.) DC. var. pruriens is a leguminous plant whose seeds have been used in traditional medicine, including for the enhancement of sexual function. However, scientific evidence regarding its toxicological safety remains limited. Accordingly, the present study aimed to investigate the acute and chronic oral toxicity of the ethanolic seed extract of M. pruriens var. pruriens in Sprague–Dawley rats. Methods: Acute oral toxicity was assessed in female rats following a single oral administration of the ethanolic seed extract of M. pruriens var. pruriens at a dose of 5000 mg/kg body weight, with animals monitored for general behavior, clinical signs, and mortality over a 14-day period. Chronic oral toxicity was evaluated in female and male rats administered the ethanolic seed extract of M. pruriens var. pruriens at doses of 100, 500, and 2500 mg/kg body weight daily for 270 days. Animals were monitored for general behavior, clinical signs, and health status throughout the study. Hematological, blood chemistry, gross pathological, and histopathological assessments were conducted at study termination. Results: In the acute oral toxicity study, no mortality or treatment-related behavioral abnormalities or clinical signs were observed in female rats receiving the ethanolic seed extract of M. pruriens var. pruriens, and findings were comparable to those of the control group. In the chronic oral toxicity study, no mortality occurred in any treatment group. Although statistically significant increases or decreases were observed in certain body weight, organ weight, hematological, and blood biochemical parameters compared with the control group, all values remained within established reference ranges. When considered together with the absence of abnormal behavioral changes, clinical signs, and gross pathological or histopathological alterations in major organs, these findings indicate that long-term oral administration of the ethanolic seed extract of M. pruriens var. pruriens did not result in chronic toxicity. Conclusions: The ethanolic seed extract of M. pruriens var. pruriens did not produce acute or chronic oral toxicity in Sprague–Dawley rats. Nevertheless, further clinical investigations are recommended to confirm its long-term safety for human use. Full article

Propylparaben (PP) is a widely used preservative in cosmetics, pharmaceuticals, and food products, and its potential toxicity to non-target aquatic invertebrates remains a concern. This study used the freshwater snail Biomphalaria glabrata as a model organism to evaluate the toxic effects of PP through acute and chronic exposures at embryonic, newly hatched, and adult stages. Acute exposure experiments showed concentration-dependent mortality and developmental inhibition, with LC₅₀ values of 36.69 mg/L (embryos, 168 h), 33.48 mg/L (newly hatched snails, 96 h), and 57.05 mg/L (adults, 72 h). Chronic exposure of adult snails to 10–49 mg/L PP for 21 days significantly reduced growth and reproductive output, and no embryo masses were observed at concentrations ≥ 25 mg/L. Histological observations revealed progressive damage to the hepatopancreas and gonads. These results demonstrate that PP induces multiple toxic effects in B. glabrata, affecting survival, growth, reproduction, and tissue structure under both acute and chronic exposure conditions. The findings provide experimental evidence for evaluating the ecological risks of paraben contamination in freshwater ecosystems. Full article

Hypertension is a globally prevalent chronic cardiovascular disease, with angiotensin-converting enzyme (ACE) serving as a key target for therapeutic intervention. Synthetic ACE inhibitors have side effects, making natural food-derived ACE-inhibitory peptides a research hotspot owing to safety advantages. Softshell turtle (Pelodiscus sinensis) bone collagen (STBC) has potential bioactivity, but its ACE-inhibitory peptides have not been systematically investigated. This study used computer-aided screening: STBC α1(I) (K7FHL1) and α2(I) (K7G8R1) sequences from UniProt were processed via SignalP 5.0. BIOPEP-UWM analysis showed ACE-inhibitory peptide frequencies of 0.8947 and 0.9261 in the two chains, confirming STBC as a high-quality precursor. Papain-ficin was selected as the optimal enzymatic system via simulation; 105 potential novel peptides were obtained after toxicity/allergenicity prediction. Twenty-seven highly active peptide fragments were screened out via pLM4ACE, and four peptide fragments with relatively high binding energy (QICVCDS, DVWK, IIEY, APMDVG) were identified through molecular docking. These peptides (molecular weight: 536.6–766.9 Da) possessed excellent physicochemical properties and pharmacokinetic characteristics, while bioinformatics analysis revealed that they could target and regulate SRC/HSP90AA1 to modulate the renin-angiotensin system (RAS). This study provides an efficient strategy for the high-value utilization of softshell turtle resources and the development of food-derived ACE-inhibitory peptides. Full article

Chronic myeloid leukemia (CML) has undergone a significant shift over the past two decades, transitioning from a fatal malignancy to a chronic, highly manageable disease with near-normal life expectancy for most patients. This transformation has been driven by the development of BCR-ABL1-targeted tyrosine kinase inhibitors (TKIs), which have enabled durable disease control and deep molecular responses (DMRs) in the majority of patients with chronic-phase CML. As long-term survival outcomes have plateaued across available agents, contemporary management has shifted beyond disease suppression toward optimizing long-term safety, quality of life, and the achievement of treatment-free remission (TFR). This review summarizes current evidence on molecular monitoring strategies, the comparative efficacy and toxicity profiles of first-, second-, and third-generation TKIs, and emerging advances in response assessment. Patient-centered TKI selection is discussed in the context of cardiovascular risk, comorbidities, treatment tolerability, and survivorship goals, reflecting the growing emphasis on individualized therapy in chronic-phase CML. Molecular monitoring strategies are examined in parallel, highlighting the clinical importance of early and sustained DMRs in guiding therapeutic decisions and TFR eligibility. Although RT-qPCR remains the standard for molecular monitoring, emerging high-sensitivity techniques such as digital droplet PCR and next-generation sequencing provide complementary value by improving the detection of low-level residual disease, refining risk stratification, and enabling earlier identification of resistance. Emerging therapeutic strategies and advances in response assessment further highlight ongoing efforts to enhance the depth and durability of remission while minimizing long-term toxicity. These developments support a more precise, individualized, and outcome-driven approach to modern CML management. Full article

The widespread occurrence of fluoride pollution in water bodies and its toxic effects on aquatic organisms have raised significant environmental concerns; however, studies on water quality criteria for fluoride remain relatively limited. This study aimed to derive such criteria and assess the ecological risks of fluoride in China’s surface waters, for the reference of readers. Acute and chronic toxicity data were collected globally, covering 34 species (14 families, 4 phyla) and 7 species (5 families, 3 phyla), respectively. Using species sensitivity distribution (SSD) methods, the short-term water quality criterion (SWQC) and long-term water quality criterion (LWQC) were derived as 17.47 mg/L and 3.334 mg/L. Ecological risk assessment based on the risk quotient (RQ) identified several high-risk areas among 32 major river and lake basins, with RQ values of 6.326 (Xihe River), 1.953 (Ebinur Lake), 1.368 (Chagan Lake), and 1.158 (Shahe River). At the provincial level, Guangxi Zhuang Autonomous Region showed as no risk (RQ = 0.0001140), while other regions were classified as moderate or low risk. This study achieved its objectives of deriving water quality criteria for fluoride and conducting an ecological risk assessment for surface waters in China. It also highlights current limitations, including insufficient fluoride toxicity data and the frequent oversight of key indicators in existing assessments. Future research could focus on improving water quality criteria derivation and risk assessment methods through integrated predictive modeling and expanded toxicity datasets. Full article

Nanotechnology has emerged as a transformative tool in animal production, offering novel strategies to enhance productivity, health, and product quality. Among trace elements, selenium (Se) plays an essential role in antioxidant defence, immune regulation, and redox balance through its incorporation into selenoproteins. Selenium nanoparticles (SeNPs), synthesized via chemical, physical, or biological methods, have shown superior bioavailability, stability, and lower toxicity compared to traditional organic and inorganic selenium forms. This review explores the synthesis, physicochemical properties, and metabolic fate of SeNPs, emphasizing their advantages in poultry production systems. In poultry, SeNPs exhibit potent antioxidant and anti-stress effects by enhancing the activity of glutathione peroxidase, superoxide dismutase, and thioredoxin reductase, thereby mitigating lipid peroxidation and oxidative tissue damage. Their immunomodulatory effects are linked to improved lymphocyte proliferation, cytokine regulation, and increased immunoglobulin levels under normal and stress conditions. SeNP supplementation has been associated with enhanced growth performance, feed efficiency, carcass quality, and reproductive outcomes in broilers, layers, and quails. Furthermore, selenium nanoparticles have demonstrated therapeutic potential in preventing or alleviating chronic diseases such as cancer, diabetes, cardiovascular dysfunction, and neurodegenerative disorders. SeNPs also serve as biofortification agents, increasing selenium deposition in poultry meat and eggs, thus improving their nutritional value for human consumption. However, selenium’s narrow safety margin requires careful dose optimization to avoid potential toxicity. This review highlights the multifaceted benefits of selenium nanoparticles in poultry nutrition and health, while underscoring the need for further studies on grey SeNPs, long-term safety, and regulatory frameworks. Integrating SeNPs into poultry production represents a promising strategy to bridge animal health, food security, and public nutrition. Full article

Antibiotics have become an integral part of human life and production. The presence of sulfachloropyridazine (SCP), one of the most ubiquitous antibiotics, in water has been a growing concern owing to its long persistence and the difficulty in removing it by conventional water treatment processes. This study introduced ozone (O₃)-activated sodium percarbonate (SPC) as an innovative technique of advanced oxidation processes (AOPs), and the degradation of SCP from water by this method was thoroughly investigated. The impact of a variety of parameters, such as the dosage of SPC, the dosage of O₃, the pH value, and water matrix constituents, on the removal of SCP was evaluated with regard to the pseudo-first-order kinetic model. It was found that the removal effectiveness of SCP improved initially and then decreased with the rising dosage of SPC, with an optimal SPC dose achieved at 20 mg/L. Moreover, •OH, ${\mathrm{O}}_2^{•-}$ and ¹O₂ played important roles during SCP degradation based on radical quenching tests and electron paramagnetic resonance (EPR) tests. The SCP degradation pathways were predicted using density functional theory (DFT), which primarily involves the cleavage of S-C or S-N bonds and Smiles-type rearrangements, accompanied by hydroxylation. Furthermore, the toxicity of degradation intermediates was evaluated by the ECOSAR 1.1 software in terms of acute toxicity and chronic toxicity, and most of them exhibited lower levels of toxicity. The results can expand the research scope of SPC and reveal significant insights for SPC’s application in controlling antibiotic contamination. 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

Chagas disease remains a significant neglected tropical disease that predominantly affects vulnerable populations in rural, low-income areas of Latin America. The management of this condition is severely hindered by the limitations of current therapies, which are characterized by substantial toxicity, diminished efficacy during the chronic phase, and the emergence of parasitic resistance. Given the promising activity of SB-83 (a 2-aminothiophenic derivative) against Leishmania spp., the present study sought to evaluate its trypanocidal activity against Trypanosoma cruzi. The results showed that SB-83 exhibited potent inhibitory effects on the epimastigote forms of T. cruzi (IC₅₀ = 6.23 ± 0.84 μM), trypomastigotes (EC₅₀ = 7.31 ± 0.52 μM) and intracellular amastigotes (EC₅₀ = 5.12 ± 0.49 μM). Furthermore, the cellular proliferation assay results indicated CC₅₀ values of 77.80 ± 2.05 µM for LLC-MK2 CCL-7 and 24.21 ± 1.2 µM for Vero CCL-87, with a selectivity index above 10 for LLC-MK2 cells. In addition, the compound increased TNF-α, IL-12, nitric oxide, and ROS while decreasing IL-10. Moreover, in silico and in vitro assays confirmed its binding to trypanothione reductase, disrupting redox balance. Flow cytometry further revealed apoptosis induction in trypomastigotes, whereas electron microscopy showed cellular disruption and organelle disorganization. Therefore, SB-83 demonstrated potent activity against the TcI-resistant strain linked to Chagas cardiomyopathy at non-toxic concentrations for host cells, supporting its potential as a therapeutic candidate. Full article