RESUMEN
Quinones are among the most important components in natural organic matter (NOM) for redox reactions; however, no quinones in complex environmental media have been identified. To aid the identification of quinone-containing molecules in ultracomplex environmental samples, we developed a chemical tagging method that makes use of a Michael addition reaction between quinones and thiols (-SH) in cysteine (Cys) and cysteine-contained peptides (CCP). After the tagging, candidates of quinones in representative aqueous environmental samples (water extractions of biochar) were identified through high-resolution mass spectrometry (HRMS) analysis. The MS and UV spectra analysis showed rapid reactions between Cys/CCP and model quinones with ß-carbon from the same benzene ring available for Michael addition. The tagging efficiency was not influenced by other co-occurring nonquinone representative compounds, including caffeic acid, cinnamic acid, and coumaric acid. Cys and CCP were used to tag quinones in water extractions of biochars, and possible candidates of quinones (20 and 53 based on tagging with Cys and CCP, respectively) were identified based on the HRMS features for products of reactions with Cys/CCP. This study has successfully demonstrated that such a Michael addition reaction can be used to tag quinones in complex environmental media and potentially determine their identities. The method will enable an in-depth understanding of the redox chemistry of NOM and its critical chemical compositions and structures.
Asunto(s)
Cisteína , Espectrometría de Masas , Péptidos , Quinonas , Cisteína/química , Péptidos/química , Quinonas/química , Carbón Orgánico/químicaRESUMEN
Two new strains JP48T and JP55 affiliated with the acidobacterial class Terriglobia have been isolated from fen soil sampled in the Fichtelgebirge Mountains near Bayreuth, Germany. Both strains were Gram-stain-negative, non-motile, non-spore-forming rods that divide by binary fission, segregate exopolysaccharide-like material and form capsules. Strains JP48T and JP55 grew at 4-36 °C (optimum at 27 °C), pH 3.6-7.3 (optimum at pH 4.6-5.5) and with NaCl concentrations of 0-3% (optimum at 1.0%; w/v). Strains JP48T and JP55 grew aerobically on a wide range of organic substrates including mono- and oligosaccharides, amino acids and short-chained fatty acids. MK-8 was identified as the major respiratory quinone. The major fatty acids for strains JP48T and JP55 were iso-C15â:â0, C16â:â1 ω7c, C16â:â0 and iso-diabolic acid. Phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, lysophophatidylethanolamine, phosphatidylcholine, unidentified glyco- and glycophospholipids, and unidentified high mass lipid species were the major polar membrane lipids. The G+C content of strains JP48T and JP55 was 57.4 and 57.2 mol%, respectively. The genomes of strains JP48T and JP55 contained nine potential secondary metabolite regions encoding for the compound classes NRPS(-like), T3PKS, terpene, or lanthipeptide class IV. Phylogenetic reconstruction and 16S rRNA gene sequence similarities of 98.3 and 96.9% identified Edaphobacter dinghuensis DHF9T and Edaphobacter lichenicola DSM 104462T as the most closely related type strains to strains JP48T and JP55. Based on their phenotype, phylogeny and chemotaxonomy, we propose the novel species Edaphobacter paludis sp. nov. (type strain JP48T=DSM 109919T=CECT 30269T; additional strain JP55=DSM 109920=CECT 30268) within the class Terriglobia of the phylum Acidobacteriota.
Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Microbiología del Suelo , ARN Ribosómico 16S/genética , Ácidos Grasos/química , ADN Bacteriano/genética , Alemania , Vitamina K 2/análogos & derivados , Quinonas/análisis , Acidobacteria/genética , Acidobacteria/clasificación , Acidobacteria/aislamiento & purificación , Fosfolípidos/químicaRESUMEN
BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Angiotensina II , Endotelio Vascular , Células Endoteliales de la Vena Umbilical Humana , Hipertensión , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III , Óxido Nítrico , Angiotensina II/farmacología , Animales , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Hipertensión/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Óxido Nítrico/metabolismo , Ratones , Salvia/química , Endotelina-1/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Quinonas/farmacología , Simulación del Acoplamiento Molecular , Presión Sanguínea/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Quinones represent a class of crude organic compounds ubiquitously distributed in nature. Their distinctive quinone-type structure confers upon them unique properties and applications. Quinones demonstrate significant biological activities, including antioxidant, antimicrobial, and antitumor properties. Additionally, they demonstrate noteworthy physicochemical characteristics, including excellent dyeing properties and stability. Given their diverse qualities, quinones hold significant promise for applications in industrial manufacturing, healthcare, and food production, thus garnering considerable attention in recent years. While there is a growing body of research on quinones, the existing literature falls short of providing a comprehensive review encompassing recent advancements in this field along with established knowledge. This paper offers a comprehensive review of research progress for quinones, encompassing structural classification, source synthesis, extraction methods, properties, functions, and specific applications. It serves as a reference and theoretical foundation for the further development and utilization of quinones.
Asunto(s)
Antiinfecciosos , Antioxidantes , Quinonas , Quinonas/química , Quinonas/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antioxidantes/farmacología , Antioxidantes/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
Psoriasis, which severely affects the sufferer's life quality, is a chronic skin disease still lacking satisfactory medication. Recently, signal transducer and activator of transcription 3 (STAT3) was revealed playing an important role in the progression of psoriasis. In this paper, a total of 59 quinone derivatives with various scaffolds were designed, synthesized, and evaluated for antipsoriatic potential as STAT3 inhibitors. Among them, 15e was identified as the most potent antipsoriatic agent and could bind to STAT3; reduce both total and phosphorylated STAT3 levels, inhibit the nuclear translocation of STAT3; and, therefore, inhibit the transcription and expression of the propsoriatic factor IL-17A. In vivo experiments on mice showed that the topical application of 15e was effective in alleviating IMQ-induced psoriasis without noticeable side effects. In all, this research rendered 15e as a promising drug candidate for psoriasis.
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Diseño de Fármacos , Psoriasis , Factor de Transcripción STAT3 , Psoriasis/tratamiento farmacológico , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Animales , Humanos , Ratones , Interleucina-17/metabolismo , Interleucina-17/antagonistas & inhibidores , Quinonas/farmacología , Quinonas/síntesis química , Quinonas/uso terapéutico , Quinonas/química , Relación Estructura-Actividad , Ratones Endogámicos BALB CRESUMEN
L-Cysteine (Cys)-activatable photosensitizer 3 was designed and synthesized based on hypocrellin B (1). Cys is a novel tumor-associated biomarker. 3 exhibited negligible photosensitizing ability without Cys. However, when 1 was released from 3 by reaction with Cys, the photosensitizing activity was restored. Furthermore, 3 showed selective and effective photo-cytotoxicity against only cancer cells such as HeLa and A549 cells that highly express Cys when irradiated with 660 nm light, which is inside the phototherapeutic window.
Asunto(s)
Antineoplásicos , Cisteína , Perileno , Fármacos Fotosensibilizantes , Quinonas , Humanos , Quinonas/química , Quinonas/farmacología , Quinonas/síntesis química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Perileno/química , Perileno/análogos & derivados , Perileno/farmacología , Perileno/síntesis química , Cisteína/química , Células HeLa , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Células A549 , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Supervivencia Celular/efectos de los fármacos , FotoquimioterapiaRESUMEN
Human NAD(P)H-quinone oxidoreductase1 (HNQO1) is a two-electron reductase antioxidant enzyme whose expression is driven by the NRF2 transcription factor highly active in the prooxidant milieu found in human malignancies. The resulting abundance of NQO1 expression (up to 200-fold) in cancers and a barely detectable expression in body tissues makes it a selective marker of neoplasms. NQO1 can catalyze the repeated futile redox cycling of certain natural and synthetic quinones to their hydroxyquinones, consuming NADPH and generating rapid bursts of cytotoxic reactive oxygen species (ROS) and H2O2. A greater level of this quinone bioactivation due to elevated NQO1 content has been recognized as a tumor-specific therapeutic strategy, which, however, has not been clinically exploited. We review here the natural and new quinones activated by NQO1, the catalytic inhibitors, and the ensuing cell death mechanisms. Further, the cancer-selective expression of NQO1 has opened excellent opportunities for distinguishing cancer cells/tissues from their normal counterparts. Given this diagnostic, prognostic, and therapeutic importance, we and others have engineered a large number of specific NQO1 turn-on small molecule probes that remain latent but release intense fluorescence groups at near-infrared and other wavelengths, following enzymatic cleavage in cancer cells and tumor masses. This sensitive visualization/quantitation and powerful imaging technology based on NQO1 expression offers promise for guided cancer surgery, and the reagents suggest a theranostic potential for NQO1-targeted chemotherapy.
Asunto(s)
NAD(P)H Deshidrogenasa (Quinona) , Neoplasias , Humanos , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/genética , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Neoplasias/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Animales , Quinonas/farmacología , Quinonas/metabolismo , Terapia Molecular DirigidaRESUMEN
A key challenge in oxidative potential (OP) assays is to accurately assess the cumulative impact of redox-active aerosol species rather than only their individual effects. This study investigates the OP of single and combined mixtures of 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), 9,10-phenanthrenequinone (9,10-PQ), 1,4-benzoquinone (1,4-BQ), Cu, Fe, Mn, and Zn in standard ascorbic acid (OPAA) and the synthetic respiratory tract lining fluid (OPRTLF) assays. In both OPAA and OPRTLF, binary mixtures showed additive and synergistic effects in the presence of 1,2-NQ. The mixture of Cu and Zn showed substantial synergisms in both assays, while the mixtures in the absence of 1,2-NQ primarily induced antagonistic effects. For the first time, we propose linear equations to improve the prediction of OP values by considering the impacts of synergistic and antagonistic effects. Under this approach, we observed that the potential effects caused by binary mixtures in ambient particulate matter (PM) samples could account for up to 68 % of the PM-OP values in Fez, Morocco (OPmAA: 0.34 nmol min-1 µg-1 and OPmRTLF: 0.18 nmol min-1 µg-1). The present study improves the understanding of effects of chemical interaction of potentially toxic substances that are important in the understanding of PM-induced oxidative stress in the human body.
Asunto(s)
Ácido Ascórbico , Oxidación-Reducción , Quinonas , Ácido Ascórbico/farmacología , Ácido Ascórbico/química , Quinonas/química , Metales/toxicidad , Material Particulado/toxicidad , Material Particulado/análisisRESUMEN
Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.
Asunto(s)
Chalcona , Glucocorticoides , Osteoporosis , Quinonas , Ratas Sprague-Dawley , Animales , Osteoporosis/inducido químicamente , Osteoporosis/prevención & control , Osteoporosis/metabolismo , Osteoporosis/tratamiento farmacológico , Ratas , Quinonas/farmacología , Chalcona/análogos & derivados , Chalcona/farmacología , Glucocorticoides/efectos adversos , Antiinflamatorios/farmacología , Densidad Ósea/efectos de los fármacos , Masculino , Femenino , Dexametasona/farmacologíaRESUMEN
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) has been identified to induce acute toxicity to multifarious aquatic organisms at exceptionally low concentrations. The ubiquity and harmful effects of 6PPD-Q emphasize the critical need for its degradation from water ecosystems. Herein, we explored the transformation of 6PPD-Q by an ultraviolet-activated peroxymonosulfate (UV/PMS) system, focusing on mechanism, products and toxicity variation. Results showed that complete degradation of 6PPD-Q was achieved when the initial ratio of PMS and 6PPD-Q was 60:1. The quenching experiments and EPR tests indicated that SO4â¢- and â¢OH radicals were primarily responsible for 6PPD-Q removal. Twenty-one degradation products were determined through high-resolution orbitrap mass spectrometry, and it was postulated that hydroxylation, oxidative cleavage, quinone decomposition, ring oxidation, as well as rearrangement and deamination were the major transformation pathways of 6PPD-Q. Toxicity prediction revealed that all identified products exhibited lower acute and chronic toxicities to fish, daphnid and green algae compared to 6PPD-Q. Exposure experiments also uncovered that 6PPD-Q considerably reduced the community diversity and altered the community assembly and functional traits of the sediment microbiome. However, we discovered that the toxicity of 6PPD-Q degradation solutions was effectively decreased, suggesting the superior detoxifying capability of the UV/PMS system for 6PPD-Q. These findings highlight the underlying detrimental impacts of 6PPD-Q on aquatic ecosystems and enrich our understanding of the photochemical oxidation behavior of 6PPD-Q.
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Rayos Ultravioleta , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Sedimentos Geológicos/química , Peróxidos/química , Animales , Microbiota , Quinonas/química , Oxidación-ReducciónRESUMEN
A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped, designated strain CAU 1642 T, was isolated from a Salicornia herbacea collected from a tidal flat in the Yellow Sea. Strain CAU 1642 T grew optimally at pH 8.0 and 30 °C. The highest 16S rRNA gene sequence similarity was 97.25%, with Pseudomarinomonas arenosa CAU 1598 T, and phylogenetic analysis indicated that strain CAU 1642 T belongs to the genus Pseudomarinomonas. The major cellular fatty acids were iso-C15:0, iso-C16:0, and summed feature 9 (iso-C17:1ω9c and/or 10-methyl C16:0). Ubiquinone-8 was the major respiratory quinone. The draft genome of strain CAU 1642 T was 4.5 Mb, with 68.7 mol% of G + C content. The phylogenetic, phenotypic, and chemotaxonomic analysis data reveal strain CAU 1642 T to be of a novel genus in the family Lysobacteraceae, with the proposed name Pseudomarinomonas salicorniae sp. nov. with type strain CAU 1642 T (= KCTC 92084 T = MCCC 1K07085T).
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Composición de Base , Chenopodiaceae , ADN Bacteriano , Ácidos Grasos , Filogenia , ARN Ribosómico 16S , Chenopodiaceae/microbiología , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , Ácidos Grasos/química , ADN Bacteriano/genética , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Análisis de Secuencia de ADN , Quinonas/análisis , Ubiquinona/química , Ubiquinona/análogos & derivados , Genoma BacterianoRESUMEN
The widespread occurrence and accumulation of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone metabolite, 6PPD quinone (6PPD-Q), have been globally recognized as a critical environmental issue. However, knowledge on the adverse effects of 6PPD and 6PPD-Q on freshwater invertebrates is limited. This study investigated the effects of 6PPD and its oxidative byproduct, 6PPD-Q, on the growth and reproduction of Daphnia pulex. Through 21-day exposure experiments, we measured the uptake of 0.1, 1, and 10 µg/L 6PPD and 6PPD-Q by D. pulex and assessed the effects on growth and fecundity of D. pulex. While 6PPD and 6PPD-Q did not affect the mortality rate of D. pulex, 6PPD-Q exposure inhibited the growth of D. pulex, indicating potential ecological risks. In particular, the reproductive capacity of D. pulex remained unaffected across the tested concentrations of 6PPD and 6PPD-Q, suggesting specific toxicological pathways that warrant further investigation. This study underscored the importance of evaluating the sublethal effects of emerging contaminants such as 6PPD and 6PPD-Q on aquatic invertebrates, and highlighted the need for comprehensive risk assessments to better understand their environmental impacts.
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Daphnia , Reproducción , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/toxicidad , Reproducción/efectos de los fármacos , Daphnia/efectos de los fármacos , Daphnia/fisiología , Fenilendiaminas/toxicidad , Quinonas/metabolismo , Quinonas/toxicidad , Agua Dulce , Cladóceros/efectos de los fármacos , Cladóceros/fisiologíaRESUMEN
Nanofibers have emerged as a highly effective method for drug delivery, attributed to their remarkable porosity and ability to regulate drug release rates while minimizing toxicity and side effects. In this study, we successfully loaded the natural anticancer drugs curcumin (CUR) and hypocrellin A (HA) into pure poly(l-lactic acid) (PLLA) and PLLA-silk protein (PS) composite nanofibers through electrospinning technology. This result was confirmed through comprehensive analysis involving SEM, FTIR, XRD, DSC, TG, zeta potential, and pH stability analysis. The encapsulation efficiency of all samples exceeded 85%, demonstrating the effectiveness of the loading process. Additionally, the drug release doses were significantly higher in the composites compared to pure PLLA, owing to the enhanced crystallinity and stability of the silk proteins. Importantly, the composite nanofibers exhibited excellent pH stability in physiological and acidic environments. Furthermore, the drug-loaded composite nanofibers displayed strong inhibitory effects on cancer cells, with approximately 28% (HA) and 37% (CUR) inhibition of cell growth and differentiation within 72 h, while showing minimal impact on normal cells. This research highlights the potential for controlling drug release through the manipulation of fiber diameter and crystallinity, paving the way for wider applications of electrospun green nanomaterials in the field of medicine.
Asunto(s)
Antineoplásicos , Proliferación Celular , Curcumina , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Fibroínas , Nanofibras , Tamaño de la Partícula , Perileno , Fenol , Poliésteres , Quinonas , Curcumina/química , Curcumina/farmacología , Nanofibras/química , Fibroínas/química , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Poliésteres/química , Quinonas/química , Quinonas/farmacología , Proliferación Celular/efectos de los fármacos , Fenol/química , Perileno/química , Perileno/análogos & derivados , Perileno/farmacología , Ensayo de Materiales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Preparaciones de Acción Retardada/química , Supervivencia Celular/efectos de los fármacos , Línea Celular TumoralRESUMEN
BACKGROUND: Liver fibrosis is a prevalent pathological process in chronic liver diseases characterized by excessive extracellular matrix (ECM) deposition and abnormal angiogenesis. Notably, hepatic stellate cells (HSCs) are the primary source of ECM. Activated HSCs not only secrete numerous pro-fibrotic cytokines but also are endowed with a pro-angiogenic phenotype to promote pathological angiogenesis. Therefore, targeted modulation of HSCs has emerged as a pivotal strategy for addressing liver fibrosis. Hydroxysafflor yellow A (HSYA) is a homology of medicine and food colourant with good pharmacological activity. However, the precise mechanisms of HSYA against liver fibrosis remain unclear. PURPOSE: The objective of this study was to elucidate the impact of HSYA on liver fibrosis and pathological angiogenesis, as well as the underlying mechanisms in vitro and in vivo studies. METHODS: The efficacy and mechanisms of HSYA on TGF-ß1-induced HSCs and VEGFA-induced endothelial cells were investigated by MTT assay, EdU cell proliferation assay, cell scratch assay, Elisa assay, immunofluorescence assay, molecular docking, cell transfection assay, western blot analysis and RT-qPCR analysis. In CCl4-induced liver fibrosis mice model, H&E, Masson, and Sirius red staining were used to observe histopathology. Serum transaminase activity and liver biochemical indexes were tested by biochemical kit. Immunohistochemical, fluorescence in situ hybridization (FISH), western blot analysis and RT-qPCR analysis were implemented to determine the mechanism of HSYA in vivo. RESULTS: Herein, our findings confirmed that HSYA inhibited the proliferation, migration and activation of HSCs, as evidenced by a reduction in cell viability, relative migration rate, EdU staining intensity, and pro-fibrotic mRNAs and proteins expression in vitro. Mechanistically, HSYA played an anti-fibrotic and anti-angiogenic role by partially silencing PDGFRB in activated HSCs, thereby disrupting PDGFRB/MEK/ERK signal transduction and inhibiting the expression of HIF-1α, VEGFA and VEGFR2 proteins. Importantly, PDGFRB was a target gene of miR-29a-3p. Treatment with HSYA reversed the down-regulation of miR-29a-3p and antagonized PDGFRB signaling pathway in TGF-ß1-induced HSCs transfected with miR-29a-3p inhibitor. Consistent with our in vitro study, HSYA exhibited a good hepatoprotective effect in CCl4-induced liver fibrosis mice by reducing serum ALT and AST levels, decreasing the contents of four fibrosis indicators (HA, PIIIP, ColIV and LN) and hydroxyproline, and inhibiting the TGF-ß1/TGFBR signaling pathway. In terms of mechanisms, HSYA alleviated pathological angiogenesis in fibrotic liver by deactivating PDGFRB signaling pathway and impairing the positive expression of CD31. Subsequently, FISH results further corroborated HSYA affected the activation of HSCs and angiogenesis achieved by the concurrent upregulation of miR-29a-3p and downregulation of α-SMA and VEGFA. Additionally, treatment with HSYA also forged a link between HSCs and endothelial cells, as supported by inhibiting the aberrant proliferation of endothelial cells. CONCLUSION: Fundamentally, the current study has illustrated that HSYA ameliorates liver fibrosis by repressing HSCs-mediated pro-fibrotic and pro-angiogenic processes, which is contingent upon the regulatory effect of HSYA on the miR-29a-3p/PDGFRB axis. These findings provide compelling evidence bolstering the potential of HSYA as a therapeutic agent in liver fibrosis.
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Inhibidores de la Angiogénesis , Chalcona , Células Estrelladas Hepáticas , Cirrosis Hepática , MicroARNs , Quinonas , Animales , Cirrosis Hepática/tratamiento farmacológico , Chalcona/análogos & derivados , Chalcona/farmacología , Quinonas/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Ratones , Masculino , Inhibidores de la Angiogénesis/farmacología , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos C57BL , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Antifibróticos/farmacología , Movimiento Celular/efectos de los fármacosRESUMEN
N,N'-Substituted p-phenylenediamine quinones (PPD-Qs) are the emerging toxicant, which transform from the rubber tire antioxidant N,N'-substituted p-phenylenediamines (PPDs). Because of their potential toxic and widespread occurrence in the environment, PPD-Qs have received great attention. However, efficiently extracting PPD-Qs from complex samples is still a challenge. Herein, a cysteine functional covalent organic framework (Cys-COF) designed according to the "donor-acceptor" sites of hydrogen bonding of PPD-Qs was synthesized via click reaction and then used as solid-phase extraction (SPE) adsorbent. Cys-COF can form the seven-member ring adsorption structure with PPD-Qs via hydrogen bonding. The adsorption mechanism was tentatively revealed by density functional theory (DFT). After optimizing the Cys-COF-SPE parameters, PPD-Qs were efficiently extracted from water, soil, sediment, and fish, followed by detection using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The Cys-COF-SPE-UHPLC-MS/MS method exhibited ideal linearity (R2 ≥ 0.9932), high relative recoveries (80.4-111 %), and low limits of detection (0.0001-0.0013 ng mL-1). In addition, the bioconcentration kinetics in goldfish provides a feasible platform to investigate the toxicity and accumulated ability of PPD-Qs.
Asunto(s)
Química Clic , Cisteína , Fenilendiaminas , Quinonas , Extracción en Fase Sólida , Espectrometría de Masas en Tándem , Fenilendiaminas/química , Cisteína/química , Extracción en Fase Sólida/métodos , Espectrometría de Masas en Tándem/métodos , Quinonas/química , Quinonas/aislamiento & purificación , Química Clic/métodos , Cromatografía Líquida de Alta Presión/métodos , Animales , Límite de Detección , Adsorción , Estructuras Metalorgánicas/química , PecesRESUMEN
A Gram-staining-negative, facultative aerobic, motile strain, designated strain ZSDE20T, was isolated from the surface seawater of Qingdao offshore. Phylogenetic analysis of the 16S rRNA gene of strain ZSDE20T, affiliated it to the genus Photobacterium. It was closely related to Photobacterium lutimaris DF-42 T (98.92% 16S rRNA gene sequence similarity). Growth occurred at 4-28ºC (optimum 28ºC), pH 1.0-7.0 (optimum 7.0) and in the presence of 1-7% (w/v) NaCl (optimum 3%). The dominant fatty acids were summed feature 3 (C16:1 ω7c or/and C16:1 ω6c, 34.23%), summed feature 8 (C18:1 ω7c and C18:1 ω6c, 10.36%) and C16:0 (20.05%). The polar lipids of strain ZSDE20T comprised phosphatidylethanolamine, phosphatidylcholine, lyso-phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol dimannoside, phosphatidylinositol mannosides and two unknown lipids. The major respiratory quinone was ubiquinone-8 (Q-8). The DNA G + C content of strain ZSDE20T was 45.6 mol%. Average nucleotide identity (ANI) values between ZSDE20T and its reference species were lower than the threshold for species delineation (95-96%); in silico DNA-DNA hybridization further showed that strain ZSDE20T had less than 70% similarity to its relatives. Based on the polyphasic evidences, strain ZSDE20T is proposed as representing a novel species of the genus Photobacterium, for which the name Photobacterium pectinilyticum sp. nov. is proposed. The type strain is ZSDE20T (= MCCC 1K06283T = KCTC 82885 T).
Asunto(s)
Composición de Base , ADN Bacteriano , Ácidos Grasos , Photobacterium , Filogenia , ARN Ribosómico 16S , Agua de Mar , Agua de Mar/microbiología , ARN Ribosómico 16S/genética , Photobacterium/genética , Photobacterium/clasificación , Photobacterium/aislamiento & purificación , Photobacterium/metabolismo , Photobacterium/fisiología , ADN Bacteriano/genética , Ácidos Grasos/análisis , Ácidos Grasos/química , China , Técnicas de Tipificación Bacteriana , Hibridación de Ácido Nucleico , Análisis de Secuencia de ADN , Quinonas/análisis , Fosfolípidos/análisisRESUMEN
Carthamus tinctorius L. (Safflower) is extensively used as a functional food and herbal medicine, with its application closely associated with hydroxysafflor yellow A (HSYA). However, the low oral bioavailability of HSYA in safflower extract (SFE) limits its health benefits and application. Our study found that co-administration of 250, 330, and 400 mg/kg peach kernel oil (PKO) increased the oral bioavailability of HSYA in SFE by 1.99-, 2.11-, and 2.49-fold, respectively. The enhanced bioavailability is attributed to improved lipid solubility and intestinal permeability of HSYA in SFE due to PKO. PKO is believed to modify membrane fluidity and tight junctions, increase paracellular penetration, and inhibit the expression and function of P-glycoprotein, enhancing the transcellular transport of substrates. These mechanisms suggest that PKO is an effective absorption enhancer. Our findings provide valuable insights for developing functional foods with improved bioavailability.
Asunto(s)
Disponibilidad Biológica , Carthamus tinctorius , Chalcona , Extractos Vegetales , Prunus persica , Quinonas , Chalcona/química , Chalcona/análogos & derivados , Chalcona/farmacología , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/metabolismo , Quinonas/química , Quinonas/metabolismo , Carthamus tinctorius/química , Animales , Prunus persica/química , Prunus persica/metabolismo , Humanos , Aceites de Plantas/química , Masculino , Ratas Sprague-Dawley , Ratas , Absorción Intestinal/efectos de los fármacosRESUMEN
Two Gram-stain-negative, aerobic, rod-shaped, non-endospore-forming and motile bacterial strains, designated IT1137T and S025T, were isolated from an intertidal sediment sample collected from the Fildes Peninsula (King George Island, Maritime Antarctica) and a soil sample under red snow in the Ny-Ålesund region (Svalbard, High Arctic), respectively. The 16S rRNA gene sequence similarity values grouped them in the genus Pseudomonas. The two strains were characterized phenotypically using API 20E, API 20NE, API ZYM and Biolog GENIII tests and chemotaxonomically by their fatty acid contents, polar lipids and respiratory quinones. Multilocus sequence analysis (concatenated 16S rRNA, gyrB, rpoB and rpoD sequences), together with genome comparisons by average nucleotide identity and digital DNA-DNA hybridization, were performed. The results showed that the similarity values of the two isolates with the type strains of related Pseudomonas species were below the recognized thresholds for species definition. Based on polyphasic taxonomy analysis, it can be concluded that strains IT1137T and S025T represent two novel species of the genus Pseudomonas, for which the names Pseudomonas paeninsulae sp. nov. (type strain IT1137T=PMCC 100533T=CCTCC AB 2023226T=JCM 36637T) and Pseudomonas svalbardensis sp. nov. (type strain S025T=PMCC 200367T= CCTCC AB 2023225T=JCM 36638T) are proposed.
Asunto(s)
Técnicas de Tipificación Bacteriana , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Tipificación de Secuencias Multilocus , Hibridación de Ácido Nucleico , Filogenia , Pseudomonas , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Microbiología del Suelo , ARN Ribosómico 16S/genética , Pseudomonas/genética , Pseudomonas/clasificación , Pseudomonas/aislamiento & purificación , Sedimentos Geológicos/microbiología , ADN Bacteriano/genética , Regiones Árticas , Regiones Antárticas , Ácidos Grasos/análisis , Svalbard , Composición de Base , Quinonas/análisisRESUMEN
Substituted p-phenylenediamines (PPDs), a class of antioxidants, have been widely used to extend the lifespan of rubber products, such as tires and pipes. During use, PPDs will generate their quinone derivatives (PPD-Qs). In recent years, PPDs and PPD-Qs have been detected in the global environment. Among them, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), the oxidation product of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), has been identified as highly toxic to coho salmon, with the lethal concentration of 50 % (LC50) being 95 ng/L, highlighting it as an emerging pollutant of great concern. This review summarizes the physicochemical properties, global environmental distribution, bioaccessibility, potential toxicity, human exposure risk, and green measures of PPDs and PPD-Qs. These chemicals exhibit lipophilicity, bioaccumulation potential, and poor aqueous stability. They have been found in water, air, dust, soil, and sediment worldwide, indicating their significance as emerging pollutants. Notably, current studies have identified electronic waste (e-waste), such as discarded wires and cables, as a non-negligible source of PPDs and PPD-Qs, in addition to tire wear. PPDs and PPD-Qs exhibit strong bioaccumulation in aquatic organisms and mammals, with a tendency for biomagnification within the food web, posing health threats to humans. Available toxicity data indicate that PPDs and PPD-Qs have negative effects on aquatic organisms, mammals, and invertebrates. Acute exposure leads to death and acute damage, and long-term exposure can cause a series of adverse effects, including growth and development toxicity, reproductive toxicity, neurotoxicity, intestinal toxicity, and multi-organ damage. This paper discusses current research gaps and offers recommendations to understand better the occurrence, behavior, toxicity, and environmental exposure risks of PPDs and PPD-Qs.
Asunto(s)
Antioxidantes , Contaminantes Ambientales , Fenilendiaminas , Fenilendiaminas/toxicidad , Humanos , Contaminantes Ambientales/toxicidad , Quinonas/toxicidad , Exposición a Riesgos Ambientales , Monitoreo del AmbienteRESUMEN
BACKGROUND: Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. METHODS: En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. RESULTS: The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. CONCLUSIONS: The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.