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Frontiers in Nutrition 2024Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that can be found in various food products, including those intended for infants. Due to their...
Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that can be found in various food products, including those intended for infants. Due to their potential health risks, it is crucial to develop sensitive analytical methods for the accurate determination of PAHs in infant foods. This study describes the development and validation of a highly sensitive method for the quantification of European PAH markers, namely benzo[a]pyrene, benzo[a]anthracene, chrysene, and benzo[b]fluoranthene, using gas chromatography-tandem mass spectrometry (GC-MS/MS), in baby food samples. The first step was the optimization of the sample preparation procedure, performed using different methods based on the QuEChERS approach, also testing different extraction solvents. Several factors such as extraction efficiency, selectivity, and recovery were evaluated to choose the most effective procedure for sample preparation. Furthermore, the GC-MS/MS method was optimized, evaluating parameters such as linearity, sensitivity, accuracy, and robustness using spiked infant food samples. The method demonstrated excellent linearities with a correlation coefficient higher than 0.999 over a wide concentration range, and limits of detection and limits of quantification in the range 0.019-0.036 μg/kg and 0.06-0.11 μg/kg, respectively. Extraction recoveries were between 73.1 and 110.7%, with relative standard deviations always lower than 8%. These findings are compliant with the indications of the European Commission (Reg. 836/2011). To assess the applicability of the method to official control activities, a survey was conducted on commercially available infant food products. Four markers were determined in commercial samples belonging to different food categories for infants and young children. The outcome of this monitoring showed that PAH contamination, in all samples, was below the quantification limits. In conclusion, the developed GC-MS/MS method provides a highly sensitive and reliable approach for the determination of PAHs in baby foods. The optimized sample preparation, instrumental parameters, and validation results ensure accurate quantification of 4 PAHs even at trace levels. This method could contribute to the assessment of PAH exposure in infants and it could support regulatory efforts to ensure the safety and quality of infant food products with regular monitoring.
PubMed: 38798769
DOI: 10.3389/fnut.2024.1403541 -
Novel 9-Methylanthracene Derivatives as p53 Activators for the Treatment of Glioblastoma Multiforme.Molecules (Basel, Switzerland) May 2024Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological...
Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (, , , , and ) exhibited good anti-glioma activity against U87 cells, with IC values lower than 2 μM. Notably, showed the best anti-glioma activity, with an IC value up to 0.53 μM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.
Topics: Humans; Glioblastoma; Tumor Suppressor Protein p53; Cell Line, Tumor; Apoptosis; Antineoplastic Agents; Anthracenes; Cell Proliferation; Brain Neoplasms; Proto-Oncogene Proteins; Cell Cycle Proteins
PubMed: 38792257
DOI: 10.3390/molecules29102396 -
International Journal of Molecular... May 2024can be a substantial concern, as it causes various diseases in aquaculture. An effective and green method for inhibiting is urgently required. Emodin, a naturally...
can be a substantial concern, as it causes various diseases in aquaculture. An effective and green method for inhibiting is urgently required. Emodin, a naturally occurring anthraquinone compound, was exploited as a photo-antimicrobial agent against . At the minimum inhibitory concentration of emodin (256 mg/L) to inactivate in 30 min, an 11.32% survival rate was observed under 45 W white compact fluorescent light irradiation. In addition, the antibacterial activity under natural sunlight (0.78%) indicated its potential for practical application. Morphological observations demonstrated that the cell walls and membranes of were susceptible to damage by emodin when exposed to light irradiation. More importantly, the photoinactivation of was predominantly attributed to the hydroxyl radicals and superoxide radicals produced by emodin, according to the trapping experiment and electron spin resonance spectroscopy. Finally, a light-dependent reactive oxygen species punching mechanism of emodin to photoinactivate was proposed. This study highlights the potential use of emodin in sunlight-mediated applications for bacterial control, thereby providing new possibilities for the use of Chinese herbal medicine in aquatic diseases prevention.
Topics: Emodin; Aeromonas hydrophila; Sunlight; Anti-Bacterial Agents; Microbial Sensitivity Tests; Reactive Oxygen Species
PubMed: 38791482
DOI: 10.3390/ijms25105444 -
Empagliflozin attenuates doxorubicin-induced cardiotoxicity by inhibiting the JNK signaling pathway.Biomedicine & Pharmacotherapy =... Jul 2024Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin, are pivotal therapies for heart failure. However, the effect of empagliflozin on doxorubicin-related...
BACKGROUND
Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin, are pivotal therapies for heart failure. However, the effect of empagliflozin on doxorubicin-related cardiac dysfunction remains unclear.
METHODS
Human induced pluripotent stem cell- and embryonic stem cell-derived cardiomyocytes were used to investigate the direct effect of empagliflozin on human cardiomyocytes. Then, the c-Jun amino-terminal kinases (JNK) inhibitor SP600125 was administered to the doxorubicin cardiotoxicity model in vitro and in vivo to investigate the role of JNK in empagliflozin.
RESULTS
In human stem cell-derived cardiomyocytes, pretreatment with empagliflozin attenuated doxorubicin-induced cleavage of caspase 3 and other apoptosis markers. Empagliflozin significantly attenuated doxorubicin-induced phosphorylation of JNK and p38. Inhibiting the phosphorylation of JNK (SP600125) or STAT3 attenuated doxorubicin-induced apoptosis, but inhibiting the phosphorylation of p38 did not. SP600125 inhibits the phosphorylation of STAT3 (S727), and a STAT3 (Y705) inhibitor also inhibits the phosphorylation of JNK. Empagliflozin and SP600125 attenuated doxorubicin-induced increases in reactive oxygen species (ROS) and decreases in oxidized nicotinamide adenine dinucleotide (NAD). In animal studies, empagliflozin and SP600125 attenuated doxorubicin-induced cardiac dysfunction and fibrosis.
CONCLUSIONS
Empagliflozin attenuated doxorubicin-induced apoptosis by inhibiting the phosphorylation of JNK and its downstream signaling pathways, including ROS and NAD+.
Topics: Glucosides; Benzhydryl Compounds; Doxorubicin; Cardiotoxicity; Myocytes, Cardiac; Humans; Animals; Apoptosis; MAP Kinase Signaling System; Sodium-Glucose Transporter 2 Inhibitors; Male; Reactive Oxygen Species; Anthracenes; JNK Mitogen-Activated Protein Kinases; Phosphorylation; Mice; Induced Pluripotent Stem Cells; Mice, Inbred C57BL
PubMed: 38788603
DOI: 10.1016/j.biopha.2024.116759 -
Biomedicine & Pharmacotherapy =... Jul 2024Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as...
Reynoutria japonica consisted of emodin-8-β-D-glucoside ameliorates Dermatophagoides farinae extract-induced atopic dermatitis-like skin inflammation in mice by inhibiting JAK/STAT signaling.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-β-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management.
Topics: Animals; Dermatitis, Atopic; Signal Transduction; Mice; Dermatophagoides farinae; STAT Transcription Factors; Janus Kinases; Humans; Glucosides; Cytokines; Male; Skin; Emodin; Keratinocytes; Plant Extracts; Inflammation
PubMed: 38788600
DOI: 10.1016/j.biopha.2024.116765 -
Ecotoxicology and Environmental Safety Jul 2024Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative...
Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative and anti-inflammatory properties such as diosgenin (DG) and emodin (ED) can be a therapeutic intervention targeting silica-induced pulmonary inflammation and fibrosis. Hydrophobicity and low bioavailability are the barriers that restrict the therapeutic efficacy of DG and ED against pulmonary defects. Encapsulating these APCs in polymeric nanoparticles can overcome this limitation. The present study has thus explored the anti-inflammatory and anti-fibrotic effects of polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) individually loaded with DG (DGn) or ED (EDn) and in combine DG+ED [(DG+ED)n] in respirable silica dust (RSD)-induced pulmonary fibrosis silicosis rat model. Our study found that individual and combined NPs revealed physiochemical characteristics appropriate for IV administration with sustained-drug release purposes. Physiological evaluations of RSD-induced silicosis rats suggested that no treatment could improve the body weight. Still, they reduced the lung coefficient by maintaining lung moisture. Only (DG+ED)n significantly cleared free lung silica. All interventions were found to attribute the increased per cent cell viability in BALF, reduce cytotoxicity via minimizing LDH levels, and balance the oxidant-antioxidant status in silicotic rats. The expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1) were efficiently down-regulated with NPs interventions compared to pure (DG+ED) treatment. All drug treatments significantly declined, the 8-HdG and HYP productions indicate that RSD-induced oxidative DNA damage and collagen deposition were successfully repaired. Moreover, histopathological investigations proposed that individual or combined drugs NPs interventions could decrease the fibrosis and alveolitis grades in RSD-induced silicosis rats. However, (DG+ED)n intervention significantly inhibited pulmonary fibrosis and alveolitis compared to pure (DG+ED) treatment. In conclusion, the RSD can induce oxidative stress and inflammation in rats, producing reactive oxygen species (ROS)-mediated cytotoxicity to pulmonary cells and leading to silicosis development. The IV administration of combined NP suppressed lung inflammation and collagen formation by maintaining oxidant-antioxidant status and effectively interrupting the fibrosis-silicosis progression. These results may be attributed to the improved bioavailability of DG and ED through their combined nano-encapsulation-mediated targeted drug delivery.
Topics: Animals; Diosgenin; Silicosis; Silicon Dioxide; Pulmonary Fibrosis; Rats; Emodin; Nanoparticles; Male; Dust; Oxidative Stress; Anti-Inflammatory Agents; Rats, Wistar; Lung; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 38788565
DOI: 10.1016/j.ecoenv.2024.116483 -
Toxics May 2024Soil contamination of polycyclic aromatic hydrocarbons (PAHs), especially caused by the mixture of two or more PAHs, raised great environmental concerns. However,...
Soil contamination of polycyclic aromatic hydrocarbons (PAHs), especially caused by the mixture of two or more PAHs, raised great environmental concerns. However, research on the migration and transformation processes of PAHs in soils and their interactions with native communities is limited. In this work, soil samples from uncontaminated sites around the industrial parks in Handan, Hengshui, and Shanghai were artificially supplemented with three concentrations of anthracene (Ant), 9-chloroanthracene (9-ClAnt), benzopyrene (BaP), and chrysene (Chr). Ryegrass was planted to investigate the degradation of PAHs and its interaction with native soil organisms in the constructed ryegrass-microbe-soil microcosmic system. The bacterial and fungal communities in soil were affected by PAHs; their species diversity and relative abundance changed after exposure to different concentrations of PAHs, among which , , , and bacteria were correlated to the degradation of PAHs. On the 56th day, the contents of BaP, Chr, and Ant decreased with the degradation process, while the degradation of 9-ClAnt was limited. Nineteen intermediates, including hydroxylation and carboxylated compounds, were identified. The present research would help clarify the potential interactions between PAHs and native organisms in contaminated sites, providing fundamental information for evaluating the transformation risks of PAHs in the natural environment.
PubMed: 38787140
DOI: 10.3390/toxics12050361 -
Marine Drugs Apr 2024Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to...
Metabolic Blockade-Based Genome Mining of Sea Anemone-Associated sp. S1502 Identifies Atypical Angucyclines WS-5995 A-E: Isolation, Identification, Biosynthetic Investigation, and Bioactivities.
Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to be an effective strategy to accelerate the discovery of natural products from both terrestrial and marine microorganisms. Here, the metabolic blockade-based genome mining strategy was applied to the discovery of other metabolites in a sea anemone-associated sp. S1502. We constructed a mutant sp. S1502/Δ that switched to producing the atypical angucyclines WS-5995 A-E, among which WS-5995 E is a new compound. A biosynthetic gene cluster () of the angucyclines was identified through gene knock-out and heterologous expression studies. The biosynthetic pathways of WS-5995 A-E were proposed, the roles of some tailoring and regulatory genes were investigated, and the biological activities of WS-5995 A-E were evaluated. WS-5995 A has significant anti- activity with an IC value of 2.21 μM. The production of antibacterial streptopyrroles and anticoccidial WS-5995 A-E may play a protective role in the mutual relationship between sp. S1502 and its host.
Topics: Streptomyces; Animals; Sea Anemones; Multigene Family; Anti-Bacterial Agents; Biosynthetic Pathways; Genome, Bacterial; Biological Products; Anthraquinones; Angucyclines and Angucyclinones
PubMed: 38786587
DOI: 10.3390/md22050195 -
Ultrasonics Sonochemistry Jul 2024Single-bubble sonoluminescence spectra of the following samples were recorded in the modes of standing and moving bubble in liquid near the center of its levitation...
Single-bubble sonoluminescence spectra of the following samples were recorded in the modes of standing and moving bubble in liquid near the center of its levitation under the action of ultrasound: water contaminated with additives of commercial gasoline (1.5 - 38 mg·L), water with additives of individual gasoline components (hexane, benzene, toluene, p-xylene, naphthalene, anthracene, and p-terphenyl), and solutions of these gasoline components in hexane. Characteristic bands λ of gasoline component emitters are recorded in the sonoluminescence spectra of a moving bubble for water samples contaminated with additives of commercial gasoline: 290 (p-xylene), 340 (p-terphenyl), 381, 399, 424, 449 (anthracene), and 438, 474, 516, 564 nm (C, a hydrocarbon decomposition product during sonolysis).These bands are as a spectral portrait of gasoline contamination of water: they make it possible to identify gasoline in water in the above mentioned range of its content and to find a quantitative content of individual gasoline components.
PubMed: 38776866
DOI: 10.1016/j.ultsonch.2024.106916 -
PloS One 2024In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery...
BACKGROUND
In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment.
METHODS
The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023.
RESULTS
Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion.
CONCLUSION
By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.
Topics: Anthraquinones; Humans; Neoplasms; Antineoplastic Agents; Drug Design; Molecular Docking Simulation; Computer-Aided Design; Drug Discovery
PubMed: 38776291
DOI: 10.1371/journal.pone.0301396