Search Results (725)

A surge has been observed in the use of pesticides to boost agricultural yield in order to feed the continuously increasing human population. Different types and classes of broad-spectrum insecticides are in use, and the number is constantly increasing with the introduction of new ones. Keeping in view the broad-spectrum effects of organophosphate pesticides including Malathion (MLN), their use is continuously increasing without appraising their toxic impacts on non-target organisms. The continuous rise in the use of MLN has led to its presence, persistence, and transport to water bodies globally, subsequently affecting commercially valuable aquatic organisms. The current study was conducted to assess MLN-induced hematological and biochemical toxicities in the brain of a commercially valuable indigenous major carp, rohu, Labeo rohita. The fish was exposed to an acute concentration of commercial-grade MLN. The LC₅₀ of MLN (5 µg/L) led to behavioral inconsistencies and subtle impacts on the hematology (an increase in white blood cells and a reduction in red blood cells, hemoglobin, packed cell volume level, and mean corpuscular hemoglobin concentration) and biochemistry (an increase in reactive oxygen species, lipid peroxidation, activities of antioxidant enzymes (catalase, peroxidase, superoxide dismutase, glutathione, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) but a reduction in total protein content and activity of Na⁺/K⁺ ATPases) in the brain tissues. MLN also inhibited the activity of Acetylcholinesterase, while it led to an increase in Acetylcholine. Significant changes were observed in the serum biochemical profile; for example, glucose, cholesterol, potassium, urea, and total bilirubin increased, whereas total protein, sodium, chloride, albumin, and inorganic phosphate decreased after exposure. The current study clearly classified MLN as highly toxic to rohu. Therefore, the extra-judicious use of MLN should be strictly supervised. Studies concerning the real-world concentration of pesticides should be carried out on regular basis to mitigate the echoing issue of pesticide-based pollution. Full article

In this study, the effectiveness of three choline chloride (ChCl)-based deep eutectic solvents (DESs) formed using malonic acid (MalA), glycerol (Gly), and glucose (Glu) as hydrogen bond donors and two conventional solvents (50% methanol and 50% ethanol) for ultrasonic-assisted extraction (UAE) of antioxidant compounds from four herbs (chamomile, lemon balm, nettle, and spearmint) were estimated. The antioxidant capacity (AC) of the obtained herb extracts was determined by the modified 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and cupric reducing antioxidant capacity (CUPRAC) methods. Profiles of phenolic acids, flavonoid aglycones, and flavonoid glycosides in the green and conventional herb extracts were quantitatively analyzed using ultra-performance liquid chromatography (UPLC). Among the prepared DESs, the highest antioxidant potential and total contents of phenolic acids, flavonoid aglycones, and flavonoid glycosides in herb extracts were achieved using ChCl:MalA (1:1). Unexpectedly, the selected green solvents extracted significantly lower amounts of total antioxidants from the investigated herbs than 50% alcohols. Additionally, macroelements (K, Na, Ca, Mg), micronutrients (Mn, Zn, Fe, Cu), and a toxic element (Cd) in four herbs were analyzed using inductively coupled plasma–mass spectrometry (ICP–MS). Determining the compositions of antioxidants and elements in herbs is essential for understanding their nutritive importance when applied in the food, cosmetic, and pharmaceutical industries. Full article

Advancing our understanding of pancreatic toxicity and metabolic disorders caused by environmental exposures requires innovative approaches. The pancreas, a vital organ for glucose regulation, is increasingly recognized as a target of harm from environmental chemicals and dietary factors. Traditional toxicological methods, while foundational, often fail to address the mechanistic complexities of pancreatic dysfunction, particularly under real-world conditions involving multiple exposures. New Approach Methodologies (NAMs)—including high-throughput screening (HTS), OMICS technologies, computational modeling, and advanced in vitro systems—offer transformative tools to tackle these challenges. NAMs enable the identification of mechanistic pathways, improve testing efficiency, and reduce reliance on animal testing. This commentary explores the integration of NAMs into pancreatic toxicity screening, addresses critical gaps in evaluating the cumulative risks of chemical and dietary exposures, and proposes solutions for integrating the pancreas into toxicity screening through NAMs. By highlighting recent advancements and emphasizing their adoption in environmental toxicity assessment frameworks, this work demonstrates the potential of NAMs to revolutionize environmental health research, inspire interdisciplinary collaboration, and protect public health. Full article

The environmental treatment of endocrine-disrupting compounds (EDCs) has attracted significant attention. Nonylphenol (NP), a highly toxic EDC with widespread distribution, presents an urgent challenge requiring effective removal strategies. Although microalgae-based treatments offer environmentally friendly and cost-effective solutions, the high toxicity level of NP impedes this process. Analysis was conducted on cell biomass, cell morphology, extracellular polymeric substances (EPSs), and the degradation of nonylphenol in Chlorella pyrenoidosa treated with nonylphenol and glucose. Glucose restored the algal biomass to 2.23 times its original level, reduced cellular damage, and maintained normal physiological activities. Glucose also stimulated algal metabolism and promoted the secretion of EPSs. The polysaccharide content of soluble EPSs (S-EPSs) increased by 32.7%, whereas that of the bound EPSs (B-EPSs) increased by 55.5%. The three-dimensional excitation–emission matrix fluorescence spectroscopy of B-EPS indicated that glucose enhanced tryptophan secretion. Glucose showed great potential as a biostimulant to enhance NP bioremediation efficiency in aquatic ecosystems. This finding indicates that the nonylphenol remediation of wastewater can be integrated with microalgal biomass recovery, creating opportunities for revenue generation. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis. As we age, the efficiency of the NRF2 pathway declines due to several factors including increased activity of its repressors, impaired NRF2-mediated antioxidant and cytoprotective gene expression, and potential epigenetic changes, though the precise mechanisms remain unclear. This leads to diminished antioxidant defenses, increased oxidative damage, and exacerbated metabolic dysregulation and inflammation—key contributors to age-related diseases. Given NRF2’s role in mitigating proteotoxic stress, the pharmacological modulation of NRF2 has emerged as a promising therapeutic strategy, even in aged preclinical models. By inducing NRF2, it is possible to mitigate the damaging effects of oxidative stress, metabolic dysfunction, and inflammation, thus reducing protein misfolding. The review highlights NRF2’s therapeutic implications for neurodegenerative diseases and cardiovascular conditions, emphasizing its role in improving proteostasis and redox homeostasis Additionally, it summarizes current research into NRF2 as a therapeutic target, offering hope for innovative treatments to counteract the effects of aging and associated diseases. Full article

Background: This study investigated the wound-healing potential of hispolon, a polyphenolic pigment derived from medicinal mushrooms, under diabetic conditions using both in vitro and in vivo models. Methods: In the in vitro assays, L929 fibroblast cells exposed to high glucose (33 mmol/L) were treated with hispolon at concentrations of 2.5, 5, 7.5, or 10 μmol/L. In the in vivo assays, streptozotocin-induced diabetic rats with excision wounds received daily topical applications of 0.2 g of 5% (w/w) hispolon ointment. Results: Hispolon improved cell viability; suppressed oxidative stress by reducing reactive oxygen species, lipid peroxidation, and oxidative DNA damage; and restored the reduced glutathione/oxidized glutathione ratio. The scratch assay demonstrated that hispolon at 10 μmol/L enhanced fibroblast migration impaired by high-glucose conditions. Treatment with 5% (w/w) hispolon ointment accelerated wound contraction, reduced the epithelialization time, and enhanced tissue regeneration with an efficacy comparable to that of Fespixon^® cream, as shown by histological findings of increased fibroblast activity, collagen deposition, and capillary growth. Hispolon ointment also modulated macrophage polarization in diabetic wounds by reducing M1 markers and enhancing M2 markers. In a diabetic rat dead-space-wound model, 5% (w/w) hispolon ointment reduced the levels of pro-inflammatory cytokines, increased those of anti-inflammatory cytokines and growth factors, and stimulated Type I and III collagen synthesis, effectively promoting wound healing. In incisional wounds, hispolon ointment improved the wound-breaking strength, showing results comparable to that of Fespixon^® cream. Safety assessments confirmed that hispolon ointment showed no acute dermal toxicity. These findings underscore hispolon’s potential as a promising candidate for diabetic wound management by mitigating oxidative stress, enhancing tissue regeneration, and accelerating wound healing. Full article

Cervical cancer poses a substantial threat to women’s health, underscoring the necessity for effective therapeutic agents with low toxicity that specifically target cancer cells. As cancer progresses, increased glucose consumption causes glucose scarcity in the tumor microenvironment (TME). Consequently, it is imperative to identify pharmacological agents capable of effectively killing cancer cells under conditions of low glucose availability within the TME. Previous studies showed that Gboxin, a small molecule, inhibited glioblastoma (GBM) growth by targeting ATP synthase without harming normal cells. However, its effects and mechanisms in cervical cancer cells in low-glucose environments are not clear. This study indicates that Gboxin notably enhanced autophagy, apoptosis, and ferroptosis in cervical cells under low-glucose conditions without significantly affecting cell survival under normal conditions. Further analysis revealed that Gboxin inhibited the activity of complex V and the production of ATP, concurrently leading to a reduction in mitochondrial membrane potential and the mtDNA copy number under low-glucose culture conditions. Moreover, Gboxin inhibited tumor growth under nutrient deprivation conditions in vivo. A mechanistic analysis revealed that Gboxin activated the AMPK signaling pathway by targeting mitochondrial complex V. Furthermore, increased AMPK activation subsequently promoted autophagy and reduced p62 protein levels. The decreased levels of p62 protein facilitated the degradation of Nrf2 by regulating the p62-Keap1-Nrf2 axis, thereby diminishing the antioxidant capacity of cervical cancer cells, ultimately leading to the induction of apoptosis and ferroptosis. This study provides a better theoretical basis for exploring Gboxin as a potential drug for cervical cancer treatment. Full article

Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy and chemotherapy. Sesquiterpene triterpenoids (STLs) and their semi-synthetic analogs are considered as a promising source of novel anti-tumor agents due to their low systemic toxicity and multi-target pharmacological effects on key processes associated with tumor progression. The current review aims to systematize the knowledge on the anti-glioblastoma potential of STLs accumulated over the last decade and to identify key processes in glioblastoma cells that are most susceptible to the action of STLs. An analysis of published data clearly demonstrated that STLs, which can successfully cross the blood–brain barrier, exert a complex inhibitory effect on glioblastoma cells through the induction of the “mitochondrial dysfunction–oxidative stress–apoptosis” axis, the inhibition of glucose metabolism and cell cycle phase transition, and the suppression of glioblastoma cell motility and invasion through the blockade of proneural–mesenchymal transition. Taken together, this review highlights the promising anti-glioblastoma potential of STLs, which are not only able to induce glioblastoma cell death, but also effectively affect their diffusive spread, and suggests the possible directions for further investigation of STLs in the context of glioblastoma to better understand their mechanism of action. Full article

Post-harvest deterioration of fruit quality represents a significant challenge in the dried fruit industry, particularly affecting the preservation of nutritional compounds and sensory attributes during the drying process. This research examined the potential protective effects of exogenous melatonin supplementation on the preservation of selected quality metrics and antioxidant characteristics in sun-dried apricots, utilizing a comparative analysis across disparate melatonin concentrations (10, 100, and 1000 µM). Our research findings demonstrated that melatonin treatment, particularly at 100 µM concentration, significantly enhanced quality preservation in sun-dried apricots. Specifically, the treatment resulted in improved color retention (increased L*, a*, and b* values), reduced oxidative stress markers (MDA and H₂O₂), and optimized sugar composition (glucose: 18.99 g/100 g, fructose: 12.58 g/100 g, sucrose: 15.52 g/100 g). The melatonin treatment at 100 µM concentration proved particularly effective, revealing the most significant results. Specifically, this concentration resulted in the highest β-carotene levels, reaching 223.07 mg/kg. These findings suggest promising applications for commercial-scale implementation through either dipping or spraying methods. The non-toxic nature of melatonin and its demonstrated efficacy in preserving fruit quality parameters position it as a valuable post-harvest treatment option in the fruit supply chain. This research contributes significantly to advancing sustainable post-harvest preservation strategies, though further investigation into melatonin stability and standardization of application protocols remains necessary for optimal commercial implementation. Full article

Ibuprofen (IBP) is one of the most consumed drugs in the world. It is only partially removed in wastewater treatment plants (WWTPs), being present in effluent wastewater and sewage sludge, causing the widespread introduction of IBP as an emergent xenobiotic in different environmental compartments. This study describes the use of Labrys neptuniae CSW11, recently described as an IBP degrader, through bioaugmentation processes for the removal of IBP from water under different conditions (additional carbon sources, various concentrations of glucose and IBP). L. neptuniae CSW11 showed very good results in a wide range of IBP concentrations, with 100% removal in only 4 days for 1 and 5 mg L⁻¹ IBP and 7 days for 10 mg L⁻¹, and up to 48.4% removal in 28 days for IBP 100 mg L⁻¹ when using glucose 3 g L⁻¹ as an additional carbon source. Three IBP metabolites were identified during the biotransformation process: 1-hydroxyibuprofen (1-OH-IBP), 2-hydroxyibuprofen (2-OH-IBP), and carboxyibuprofen (CBX-IBP), whose concentrations declined drastically in the presence of glucose. IBP metabolites maintained a certain degree of toxicity in solution, even when IBP was completely removed. The results indicate that L. neptuniae CSW11 can be quite effective in degrading IBP in water, but the bioaugmentation method should be improved using CSW11 in consortia with other bacterial strains able to degrade the toxic metabolites produced. A genome-based analysis of L. neptuniae CSW11 revealed different enzymes that could be involved in IBP biodegradation, and a potential metabolic pathway was proposed based on the metabolites observed and genome analysis. Full article

Definitive chemoradiotherapy (CRT) is a cornerstone of treatment for locoregionally advanced head and neck cancer (HNC). Research is ongoing on how to improve the tumor response to treatment and limit normal tissue toxicity. A major limitation in that regard is the growing occurrence of intrinsic or acquired treatment resistance in advanced cases. In this review, we will discuss how overexpression of efflux pumps, perturbation of apoptosis-related factors, increased expression of antioxidants, glucose metabolism, metallotheionein expression, increased DNA repair, cancer stem cells, epithelial-mesenchymal transition, non-coding RNA and the tumour microenvironment contribute towards resistance of HNC to chemotherapy and/or radiotherapy. These mechanisms have been investigated for years and been exploited for therapeutic gain in resistant patients, paving the way to the development of new promising drugs. Since in vitro studies on resistance requires a suitable model, we will also summarize published techniques and treatment schedules that have been shown to generate acquired resistance to chemo- and/or radiotherapy that most closely mimics the clinical scenario. Full article

Natural compounds derived from microorganisms, especially those with antioxidant and anticancer properties, are gaining attention for their potential applications in biomedical, cosmetic, and food industries. Marine fungi, such as Asteromyces cruciatus, are particularly promising due to their ability to produce bioactive metabolites through the degradation of marine algal polysaccharides. This study investigates the metabolic diversity of A. cruciatus grown on different carbon sources: glucose, Durvillaea spp., and Macrocystis pyrifera. Crude extracts of fungal biomass were analyzed for total phenolic content (TPC), antioxidant capacity (TAC), toxicity, and phenolic compound identification using ultra-high-performance liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (UHPLC-MS/MS). The analysis revealed the presence of anthraquinone compounds, including emodin (0.36 ± 0.08 mg/g DW biomass) and citrereosein in glucose medium and citrereosein and endocrocin in M. pyrifera medium. No such compounds were detected in Durvillaea spp. medium. The glucose-grown extract exhibited the highest TPC (3.09 ± 0.04 mg GAE/g DW) and TAC (39.70 ± 1.0 µmol TEq/g biomass). Additionally, no detrimental effects were observed on a neuronal cell line. These findings highlight the influence of carbon sources on the production of bioactive metabolites and their functional properties, providing valuable insights into the biotechnological potential of A. cruciatus. Full article

Identifying biomarkers of mycotoxin effects in chickens will provide an opportunity for early intervention to reduce the impact of mycotoxicosis. This study aimed to identify whether serum enzyme concentrations, gut integrity, and liver miRNAs can be potential biomarkers for fumonisin B1 (FB1), deoxynivalenol (DON), and zearalenone (ZEA) toxicity in broiler birds as early as 14 days after exposure. A total of 720 male broiler chicks were distributed to six treatment groups: T1: control group (basal diet), T2 (2 FB1 + 2.5 DON + 0.9 ZEA), T3 (5 FB1 + 0.4 DON + 0.1 ZEA), T4 (9 FB1 + 3.5 DON + 0.7 ZEA), T5 (17 FB1 + 1.0 DON + 0.2 ZEA), and T6 (21 FB1 + 3.0 DON + 1.0 ZEA), all in mg/kg diet. On d14, there were no significant differences in the body weight gain (BWG) of mycotoxin treatment groups when compared to the control (p > 0.05), whereas on d21, T6 birds showed significantly reduced BWG compared to the control (p < 0.05). On d14, birds in T6 showed significant upregulation of liver miRNAs, gga-let-7a-5p (14.17-fold), gga-miR-9-5p (7.05-fold), gga-miR-217-5p (16.87-fold), gga-miR-133a-3p (7.41-fold), and gga-miR-215-5p (6.93-fold) (p < 0.05) and elevated serum fluorescein isothiocyanate-dextran (FITC-d) concentrations, aspartate aminotransferase (AST), and creatine kinase (CK) levels compared to the control (p < 0.05). On d21, T2 to T6 birds exhibited reduced serum phosphorus, glucose, and potassium, while total protein, FITC-d, AST, and CK levels increased compared to control (p < 0.05). These findings suggest that serum FITC-d, AST, CK, and liver miRNAs could serve as biomarkers for detecting mycotoxin exposure in broiler chickens. Full article

This paper presents the results of microbial corrosion tests on M0-grade copper under conditions simulating a geological repository for radioactive waste at the Yeniseisky site (Krasnoyarsk Krai, Russia). The work used a microbial community sampled from a depth of 450 m and stimulated with glucose, hydrogen and sulfate under anaerobic conditions. It was shown that the maximum corrosion rate, reaching 9.8 µm/y, was achieved with the addition of sulfate (1 g/L) with the participation of microorganisms from the families Desulfomicrobiaceae, Desulfovibrionaceae and Desulfuromonadaceae. It was noted that the most important factor leading to copper corrosion was the accumulation of hydrogen sulfide during the activation of sulfate-reducing microorganisms of the genera Desulfomicrobium, Desulfovibrio and Desulfuromonas. During the development of the microbial community under these conditions, the content of copper can have a significant toxic effect at a concentration of more than 250 mg/L. Full article

Metformin (Met) is one of the most commonly prescribed first-line drugs for diabetes treatment. However, it has several issues, including low bioavailability, therapeutic platform, and side effects at high doses. In order to improve the therapeutic efficiency of Met, this study proposes a strategy of using Met and curcumin (Cur) to prepare Cur-Zn(II)-Met infinite coordination polymer nanoparticles (CM ICP NPs), and combining this with intraperitoneal injections, for the treatment of diabetic mice. Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), nanoparticle analysis, cytotoxicity experiments, and mice experiments were used to investigate structure, properties, and application effects. The results showed that CM ICP NPs exhibit a high drug encapsulation rate (100%), good stability, and an absence of in vivo and in vitro toxicity. The blood glucose level of diabetic mice after treatment was reduced to 6.7 ± 0.65 mmol/L at the seventh week. In terms of therapeutic mechanism, it appears that Met and Cur can synergistically regulate blood glucose in mice from multiple paths. This study provides a promising method for the treatment of diabetes using Met and other drugs. Full article