Search Results (1,283)

Plastic manufacturing involves using compounds that could be considered endocrine disruptors. Consequently, concern about the effect of these particles on the hormonal regulation of various systems, including the hypothalamic–pituitary–thyroid axis, has been increasing. By applying the Amphibian Metamorphosis Assay (AMA), the effects of irregular polystyrene microplastics (PS) MPs on the thyroid gland of Xenopus laevis were investigated. The histological effects on other organs of tadpoles were also studied. Tadpoles were exposed to 500 and 50 µg of virgin PS MP particles, (200 µm range)/L, administered by diet for 21 days. PS dietary exposure revealed statistically significant effects for the snout to vent length and the whole body length apical endpoints on day 21. The histological survey of both treatment groups revealed no noteworthy effects on the thyroid gland, digestive tract, or kidneys, but slight modifications to the liver. Mild ultrastructural modifications were detected in tadpoles’ enterocytes and hepatocytes in both treatment groups, but were likely to be reversible. Overall, our results contrast with previous research results in which effects were observed, but using different types, concentrations, and numbers of MPs. All this suggests the need for standardized methods for the environmental risk assessment of MPs/NPs (nanoplastics). Concern about the risk of NPs seems to be greater, and more studies with NP particles should be conducted. Full article

Anthocyanins are important phenolic compounds in grape skins, affecting the color, oxidation resistance, and aging ability of red wine. In recent years, global warming has had a negative effect on anthocyanin biosynthesis in grape berries. Ethylene serves as a crucial phytohormone regulating the development and ripening processes of fruit; however, the specific molecular mechanism and the regulatory network between ethylene signaling and the anthocyanin biosynthesis pathway remain incompletely understood. In this study, 400 mg/L ethephon (ETH) solution was sprayed onto the surface of grape berries at the lag phase (EL-34), and the changes in anthocyanin-related genes and metabolites were explored through transcriptomic and metabolomic analysis. The results showed that ETH treatment increased Brix and pH in mature berries. In total, 35 individual anthocyanins were detected, in which 21 individual anthocyanins were enhanced by ETH treatment. However, the anthocyanin profile was not affected by exogenous ethylene. Transcriptomics analysis showed that there were a total of 825 and 1399 differentially expressed genes (DEGs) 12 h and 24 h after treatment. Moreover, key structural genes in the anthocyanin synthesis pathway were strongly induced, including VvPAL, VvCHS, VvF3H, VvF3′5′H, VvDFR and VvUFGT. At the maturity stage (EL-38), the expression levels of these genes were still higher in EHT-treated berries than in the control. ETH treatment also influenced the expression of genes related to hormone biosynthesis and signal transduction. The ethylene biosynthesis gene (VvACO), ethylene receptor genes (VvETR2, VvERS1 and VvEIN4), ABA biosynthesis gene (VvNCED2), and ABA receptor gene (VvPYL4) were up-regulated by ETH treatment, while the auxin biosynthesis gene (VvTAA3) and seven genes of the auxin-responsive protein were inhibited by exogenous ethylene. Meanwhile, ETH treatment promoted the expression of the sugar transporter gene (VvEDL16) and two sucrose synthase genes (VvSUS2 and VvSUS6). In EHT-treated berries, 19 MYB and 23 ERF genes were expressed differently compared with the control (p < 0.05). This study provides the theoretical foundation and technical support for the regulation of anthocyanin synthesis in non-climacteric fruit. Full article

Cholinergic neuron impairment is a significant cause of cognitive decline in Alzheimer’s disease (AD), making acetylcholinesterase (AChE) a key therapeutic target. AChE inhibitors are principal drugs prescribed to alleviate symptoms in AD patients, while up to 50% of these individuals also suffer from depression, frequently treated with selective serotonin reuptake inhibitors (SSRIs). Due to the multisymptomatic nature of AD, there is a growing interest in developing multitargeted ligands that simultaneously enhance cholinergic and serotonergic tone. This study presents the synthesis of novel ligands based on functionalized piperidines, evaluated through radioligand binding assays at the serotonin transporter (SERT) and AChE and butyrylcholinesterase (BuChE) inhibition. The pharmacological results showed that some compounds exhibited moderate inhibitory activity against AChE, with one compound 19 standing out as the most potent, also displaying a moderate BuChE inhibitory activity, while showing low affinity for SERT. On the other hand, compound 21 displayed an interesting polypharmacological profile, with good and selective activity against BuChE and SERT. The results underscore the difficulty of designing promiscuous ligands for these targets and suggest that future structural modifications could optimize their therapeutic potential in AD. Full article

Fruits and vegetables are crucial components of a healthy diet, which are susceptible to pests. Therefore, the application of pesticides is a basic manner of crop chemical protection. The aim of this study was a comprehensive analysis of pesticide occurrence in 1114 samples of fruits and vegetables. A unified multi-analytical protocol was used composed of primary–secondary amine/graphitized carbon black/magnesium sulfate to purify samples with diversified profile of interfering substances. Moreover, the obtained analytical data were used to evaluate the critical acute health risk in subpopulations of children and adults within European limits criteria. Out of 550 pesticides analyzed, 38 and 69 compounds were noted in 58.6% of fruits and 44.2% of vegetables, respectively. Acetamiprid (14.1% of all detections) and captan (11.3%) occurred the most frequently in fruits, while pendimethalin (10.6%) and azoxystrobin (8.6%) occurred the most frequently in vegetables. A total of 28% of vegetable and 43% of fruit samples were multiresidues with up to 13 pesticides in dill, reaching a final concentration of 0.562 mg kg⁻¹. Maximum residue level (MRL) was exceeded in 7.9% of fruits and 7.3% of vegetables, up to 7900% MRL for chlorpyrifos in dill (0.79 mg kg⁻¹). Notably, 8 out of 38 pesticides found in fruits (21%; 1.2% for carbendazim) and 24 out of 69 compounds in vegetables (35%, 7.4% for chlorpyrifos) were not approved in the EU. Concentrations of pesticides exceeding MRL were used to assess acute health risk for children and adults. Moreover, the incidence of acute health risk was proved for children consuming parsnip with linuron (156%). In other cases, it was below 100%, indicating that Polish food is safe. The work provides reliable and representative scientific data on the contamination of fruits and vegetables with pesticides. It highlights the importance of legislative changes to avoid the occurrence of not approved pesticides in the EU, increasing food and health safety. Full article

Oenological residues may cause environmental pollution when processing does not significantly reduce volume and/or harmful conditions. The lack of proper valorisation alternatives entails high disposal costs and resource inefficiency that jeopardise the sustainability and competitiveness of the industry. Interestingly, wine by-products are underappreciated sources of multipurpose bioactive compounds, such as anthocyanins, associated with health benefits. Alternatively, transforming oenological by-products into valuable co-products will promote sustainability and thus, create new business opportunities. In this context, the present study has assessed the applicability of winery by-products (grape pomace and wine lees) as ingredients to develop new functional kombucha-analogous beverages “3S” (safe, salubrious, and sustainable) by the Symbiotic Culture of Bacteria and Yeast (SCOBY). Concerning the main results, during the kombucha’s development, the fermentation reactions modified the physicochemical parameters of the beverages, namely pH, total soluble solids, acetic acid, ethanol, and sugars, which remained stable throughout the monitored shelf-life period considered (21 days). The fermented beverages obtained exhibited high anthocyanin concentration, especially when using wine lees as an ingredient (up to 5.60 mg/L at the end of the aerobic fermentation period (10 days)) compared with the alternative beverages produced using grape pomace (1.69 mg/L). These findings demonstrated that using winery by-products for the development of new “3S” fermented beverages would provide a dietary source of bioactive compounds (mainly anthocyanins), further supporting new valorisation chances and thus contributing to the competitiveness and sustainability of the winery industries. This study opens a new avenue for cross-industry innovation, merging fermentation traditions with a new eco-friendly production of functional beverages that contribute to transforming oenological residues into valuable co-products. Full article

Fermented plant-based beverages represent promising functional foods due to their content of bioactive compounds (polyphenols, prebiotics) and viable probiotic microorganisms. Sprouted buckwheat is a rich source of bioactives and nutrients, which makes it a promising ingredient for the development of synbiotic formulations. This study aimed to optimize the fermentation process of a plant-based beverage composed of germinated buckwheat, honey, inulin, and Lactiplantibacillus plantarum (Lpb. plantarum), using Box–Behnken experimental design (BBD) and Response Surface Methodology (RSM) tools. The influence of three independent variables (inulin, honey, and inoculum concentration) was evaluated on five key response variables: total polyphenol content, flavonoid content, antioxidant activity (RSA%), pH, and starter culture viability. The optimal formulation—comprising 3% inulin, 10% honey, and 6.97 mg/100 mL inoculum—demonstrated functional stability over 21 days of refrigerated storage (4 °C), maintaining high levels of antioxidants and probiotic viability in the fermented beverage. Kinetic analysis of the fermentation process confirmed the intense metabolic activity of Lpb. plantarum, as evidenced by a decrease in pH, active consumption of reducing sugars, and organic acids accumulation. Full article

Background: Endophytic fungi are prolific sources of bioactive metabolites with potential in pharmaceutical and biotechnological applications. Methods: Here, the endophytic fungus, Alternaria alstroemeriae S6, was isolated from Veronica acinifolia (speedwell), and conducted its anti-microbial activities, whole-genome sequencing and metabolome analysis. Results: The ethyl acetate extract of this fungus exhibited strong anti-bacterial activity and the inhibition zones, induced by the fungal extract at 20 mg/mL, reached 16.25 ± 0.5 mm and 26.5 ± 0.5 mm against Gram-positive and Gram-negative bacteria. To unravel the biosynthetic potential for anti-bacterial compounds, whole-genome sequencing was conducted on A. alstroemeriae S6, resulting in a high-quality assembly of 42.93 Mb encoding 13,885 protein-coding genes. Comprehensive functional genome annotation analyses, including gene ontology (GO) terms, clusters of orthologous groups (COGs), Kyoto encyclopedia of genes and genomes (KEGG), carbohydrate-active enzymes (CAZymes), and antibiotics and secondary metabolites analysis shell (antiSMASH) analyses, were performed. According to the antiSMASH analysis, 58 biosynthetic gene clusters (BGCs), including 16 non-ribosomal peptide synthetases (NRPSs), 21 terpene synthases, 12 polyketide synthetases (PKSs), and 9 hybrids, were identified. In addition, succinic acid was identified as the major metabolite within the fungal extract, while 20 minor bioactive compounds were identified through LC-MS/MS-based molecular networking on a GNPS database. Conclusions: These findings support the biotechnological potential of A. alstroemeriae S6 as an alternative producer of succinic acid, as well as novel anti-bacterial agents. Full article

Malaria continues to pose a significant global health burden, driving the search for novel antimalarial agents to address emerging drug resistance. This study evaluated the antiplasmodial potential of Ziziphus mauritiana Lam. (Rhamnaceae) roots through an integrated phytochemical and pharmacological approach. The ethanol extract, along with its derived fractions, demonstrated potent in vitro activity against the chloroquine-sensitive Plasmodium falciparum strain 3D7 (Pf3D7), with the ethyl acetate-soluble (IC₅₀ = 11.35 µg/mL) and alkaloid-rich (IC₅₀ = 4.75 µg/mL) fractions showing particularly strong inhibition. UHPLC-DAD-ESI-QTOF-MS/MS-based molecular networking enabled the identification of thirty-two secondary metabolites (1–32), comprising twenty-five cyclopeptide alkaloids (CPAs), five of which had not yet been described (11, 20, 22, 23, 25), and seven known triterpenoids. Bioactivity-guided isolation yielded thirteen purified compounds (5, 6, 14, 26–30, 32–36), with betulinic acid (30; IC₅₀ = 19.0 µM) and zizyberenalic acid (32; IC₅₀ = 20.45 µM) exhibiting the most potent antiplasmodial effects. Computational ADMET analysis identified mauritine F (4), hemisine A (10), and nummularine R (21) as particularly promising lead compounds, demonstrating favourable pharmacokinetic properties, low toxicity profiles, and predicted activity against both family A G protein-coupled receptors and evolutionarily distinct Plasmodium protein kinases. Quantitative analysis revealed exceptionally high concentrations of key bioactive constituents, notably zizyberenalic acid (24.3 mg/g) in the root extracts. These findings provide robust scientific validation for the traditional use of Z. mauritiana in malaria treatment while identifying specific cyclopeptide alkaloids and triterpenoids as valuable scaffolds for antimalarial drug development. The study highlights the effectiveness of combining advanced metabolomics, bioassay-guided fractionation, and computational pharmacology in natural product-based drug discovery against resistant malaria strains. Full article

As potable water becomes limited, alternative water sources, such as reclaimed wastewater, for crop irrigation have gained attention. However, reclaimed wastewater for irrigation may expose edible crops to compounds of emerging concern (CECs), which may include pharmaceutics, hazardous waste, and volatile substances. Of these CECs, carbamazepine (CBZ) is of particular interest because only 7% of CBZ is filtered out during traditional wastewater treatment processing methods. Two trials were designed to evaluate the uptake and partitioning of CBZ in lettuce grown in a deep-water culture system (DWC) at low and high concentrations. The first trial (0 µg L⁻¹, 12.5 µg L⁻¹, 25 µg L⁻¹, and 50 µg L⁻¹) of CBZ had few effects on lettuce (Lactuca sativa var. capitata) growth, and low concentrations of accumulated CBZ were found in lettuce tissues. As a result, increased concentrations of CBZ were used in the second trial (0 mg L⁻¹, 21 mg L⁻¹, 41 mg L⁻¹, and 83 mg L⁻¹). Greater amounts of CBZ accumulated in plant tissues and the application of higher rates of CBZ negatively affected the growth and overall health of the lettuce. Further research is needed to determine the impacts of CECs on plant uptake and growth, as well as the environmental conditions. Full article

Hemp (Cannabis sativa L.) products have gained attention in poultry nutrition for their rich content of polyunsaturated fatty acids (PUFAs), bioactive compounds, and potential functional benefits. However, findings on their impact on laying-hen performance, egg quality, and yolk fatty acid profiles have been inconsistent. This meta-analysis aimed to evaluate the effects of dietary hemp products on laying-hen performance, egg quality traits, and yolk fatty acid composition, while exploring potential sources of heterogeneity across studies. A comprehensive literature search identified 21 studies that met the inclusion criteria. A random-effects model was used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CIs) for various outcomes, including production performance, egg quality, and yolk fatty acid profiles. Subgroup and meta-regression analyses assessed the influence of factors such as inclusion level, hen age, and hemp product type. The results showed that hemp supplementation had no significant effect on hen-day production, egg mass, feed conversion ratio, or feed intake. However, yolk redness (SMD = 4.40; 95% CI: 2.46, 6.33; p < 0.001) and yellowness (SMD = 4.45; 95% CI: 2.75, 6.16; p < 0.001) were significantly enhanced. Hemp feeding also increased n-3 PUFA levels in egg yolk, including C18:3n3, C20:5n3, and C22:6n3, while reducing saturated and monounsaturated fatty acids. Subgroup analysis indicated that inclusion levels > 10% and hen age ≤ 25 weeks were associated with slight reductions in hen-day production, whereas older hens (>25 weeks) showed increased egg weight. In conclusion, hemp products can enrich yolk pigmentation and n-3 PUFA content in eggs, supporting the production of functional, value-added eggs without compromising the laying-hen performance. Full article

Background: Brain injuries, including stroke and traumatic brain injury (TBI), pose a major healthcare challenge due to their severe consequences and complex recovery. While ischemic strokes are more common, hemorrhagic strokes have a worse prognosis. TBI often affects young adults and leads to long-term disability. A critical concern in these patients is the frequent development of chronic critical illness, compounded by metabolic disturbances and malnutrition that hinder recovery. Objective: This study aimed to compare changes in nutritional status parameters under standard enteral nutrition protocols and clinical outcomes in prolonged/chronic critically ill patients with TBI or stroke versus such a population of patients without TBI or stroke. Methods: This matched prospective–retrospective cohort study included intensive care unit (ICU) patients with TBI or stroke from the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology and patients without these conditions from the eICU-CRD database. Inclusion criteria comprised age 18–74 years, ICU stay >5 days, and enteral nutrition. Patients with re-hospitalization, diabetes, acute organ failure, or incomplete data were excluded. Laboratory values and clinical outcomes were compared between the two groups. Propensity score matching (PSM) was used to balance baseline characteristics (age, sex, and body mass index). Results: After PSM, 29 patients with TBI or stroke and 121 without were included. Univariate analysis showed significant differences in 21 laboratory parameters and three hospitalization outcomes. On day 1, the TBI/stroke group had higher hemoglobin, hematocrit, lymphocytes, total protein, and albumin, but lower blood urea nitrogen (BUN), creatinine, and glucose. By day 20, they had statistically significantly lower calcium, BUN, creatinine, and glucose. This group also showed less change in lymphocytes, calcium, and direct bilirubin. Hospitalization outcomes showed longer mechanical ventilation duration (p = 0.030) and fewer cases of acute kidney injury (p = 0.0220) in the TBI/stroke group. Conclusions: TBI and stroke patients exhibit unique metabolic patterns during prolonged/chronic critical illness, differing significantly from other ICU populations in protein/glucose metabolism and complication rates. These findings underscore the necessity for specialized nutritional strategies in neurocritical care and warrant further investigation into targeted metabolic interventions. Full article

Background: Herbal medicine represents a rich yet complex source of bioactive compounds, offering both therapeutic potential and toxicological risks. Methods: In this study, we systematically evaluated the biological effects of three traditional herbal extracts—Mentha longifolia, Scrophularia orientalis, and Echium biebersteinii—using Caenorhabditis elegans as an in vivo model. Results: All three extracts significantly reduced worm survival, induced larval arrest, and triggered a high incidence of males (HIM) phenotypes, indicative of mitotic failure and meiotic chromosome missegregation. Detailed analysis of germline architecture revealed extract-specific abnormalities, including nuclear disorganization, ectopic crescent-shaped nuclei, altered meiotic progression, and reduced bivalent formation. These defects were accompanied by activation of the DNA damage response, as evidenced by upregulation of checkpoint genes (atm-1, atl-1), increased pCHK-1 foci, and elevated germline apoptosis. LC-MS profiling identified 21 major compounds across the extracts, with four compounds—thymol, carvyl acetate, luteolin-7-O-rutinoside, and menthyl acetate—shared by all three herbs. Among them, thymol and carvyl acetate significantly upregulated DNA damage checkpoint genes and promoted apoptosis, whereas thymol and luteolin-7-O-rutinoside contributed to antioxidant activity. Notably, S. orientalis and E. biebersteinii shared 11 of 14 major constituents (79%), correlating with their similar phenotypic outcomes, while M. longifolia exhibited a more distinct chemical profile, possessing seven unique compounds. Conclusions: These findings highlight the complex biological effects of traditional herbal extracts, demonstrating that both beneficial and harmful outcomes can arise from specific phytochemicals within a mixture. By deconstructing these extracts into their active components, such as thymol, carvyl acetate, and luteolin-7-O-rutinoside, we gain critical insight into the mechanisms driving reproductive toxicity and antioxidant activity. This approach underscores the importance of component-level analysis for accurately assessing the therapeutic value and safety profile of medicinal plants, particularly those used in foods and dietary supplements. Full article

Experiences of life-threatening stimuli can induce post-traumatic stress disorder (PTSD), which is associated with long-lasting behavioral and neurochemical abnormalities. Despite its increased global incidence, the current treatment options for PTSD remain limited, highlighting the need for novel therapeutic strategies. As oxidative stress and neuroinflammation contribute to PTSD, the use of powerful antioxidants such as thiamine (B1 vitamin) compounds may counteract disease development. Young C57BL/6 mice received thiamine or benfotiamine in drinking water (each at a dose of 200 mg/kg/day) for 21 days, and for the last five days, they were subjected to rat exposure. Mice were studied for anxiety-like behavior, exploration, locomotion, grooming, social interactions, pain sensitivity, brain changes in protein carbonyl (PC), total glutathione (TG), and gene expression of distress and inflammation markers. Rat exposure induced anxiety-like behavior, excessive grooming, and alteration in locomotion, along with other abnormalities. Stressed, untreated mice had elevated levels of PC and TG in the prefrontal cortex, hippocampus, amygdala, and striatum and increased expression of Il-1β, Tnf, c-Fos, Cox-1, and Cox-2. Treatment with thiamine or benfotiamine significantly ameliorated most of these changes in the stressed groups. Thus, thiamine compounds may have therapeutic potential in patients with PTSD, owing to their antioxidant and anti-inflammatory properties. Full article

The widespread environmental dissemination of imidazole compounds necessitates robust analytical monitoring tools. This study developed a novel isotope-labeled surrogate-based high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of 21 imidazoles in water, sediment, and soil. The optimized SPE protocol using Oasis HLB cartridges achieved high recoveries, with chromatographic separation completed in 25 min. Six isotope-labeled standards effectively corrected matrix effects (−57% to 8%), yielding MQLs < 1.0 ng·L⁻¹ (water) and <1.0 μg·kg⁻¹ (sediment/soil). Validation confirmed linearity (R² > 0.995), accuracy (60–120% recovery for 20/21 analytes), and precision (relative standard deviation, RSD < 15%). Its application in Jiulong River revealed significant contamination, detecting eight imidazoles in both water (up to 49.29 ng·L⁻¹) and sediment (up to 24.01 μg·kg⁻¹). This standardized tool enables routine monitoring of pharmaceutical residues across environmental compartments, supporting regulatory frameworks. Full article

The title compound, C₂₆H₂₁BrN₂O₅ (Compound 4), was obtained via our previously described procedure with modifications, i.e., via a facile one-pot three component reaction starting from commercially available materials. Compound 4 was crystallized from nitromethane. It crystalized in a triclinic crystal system, in the P-$\overline{1}$ space group. The crystal structure of 4 is described herein. Hirsfeld surface analysis, generated by the Crystal Explorer 21 software, was used to visualize the intermolecular close contacts in the title compound. The electrostatic, dispersion, and total energies in the crystal structure were calculated using the same program. Full article