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Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and endstage renal disease, and is characterized by persistent proteinuria and decreased glomerular filtration rate. Despite extensive efforts, the increasing incidence highlights the urgent need for more effective treatments. Histone methylation is a crucial epigenetic modification, and its alteration can destabilize chromatin structure, thereby regulating the transcriptional activity of specific genes. Histone methylation serves a substantial role in the onset and progression of various diseases. In patients with DKD, changes in histone methylation are pivotal in mediating the interactions between genetic and environmental factors. Targeting these modifications shows promise in ameliorating renal histological manifestations, tissue fibrosis and proteinuria, and represents a novel therapeutic frontier with the potential to halt DKD progression. The present review focuses on the alterations in histone methylation during the development of DKD, systematically summarizes its impact on various renal parenchymal cells and underscores the potential of targeted histone methylation modifications in improving DKD outcomes.
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Nefropatias Diabéticas , Epigênese Genética , Histonas , Humanos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/terapia , Nefropatias Diabéticas/tratamento farmacológico , Histonas/metabolismo , Animais , Metilação , Processamento de Proteína Pós-Traducional , Código das HistonasRESUMO
Sucrose shows the potential of stabilizing foam system. This study systematically evaluated the mechanism by which sucrose improved foaming properties and mechanical characteristics of foams stabilized by soy protein isolate/gellan gum/guar gum ternary complex. Results showed that sucrose could bond to the surface of ternary complex or self-aggregate within the continuous phase, resulting in the neutralization of charges (nearly zero) and an increase in particle size (up to 62.54 µm). The addition of 30 % sucrose reinforced foam system with an increased foamability (305.99 %) but a longer foaming time (10 min) during foaming process. Moreover, the mechanical characteristics, including hardness, elastic strength (Power-law constant) and solid characteristic (frequency exponent), were also significantly enhanced to 1.26 N, 354.7956 and 2.5873, respectively, which were 1.65, 1.94 and 1.11 times than those of foams without sucrose. The microscopic mechanism lied in the reduced water freedom degree caused by sucrose, which generated a compact structural network around bubbles for providing a stable and stiff structure to foams. These findings will provide clear theoretical guidance for regulating mechanical characteristics of aerated foods by using sucrose as structural building blocks.
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Background: Disorders of lipid metabolism play a key role in the initiation and progression of chronic kidney disease (CKD). Recently, research on lipid metabolism in CKD has rapidly increased worldwide. However, comprehensive bibliometric analyses in this field are lacking. Therefore, this study aimed to evaluate publications in the field of lipid metabolism in CKD over the past 20 years based on bibliometric analysis methods to understand the important achievements, popular research topics, and emerging thematic trends. Methods: Literature on lipid metabolism in CKD, published between 2004 and 2023, was retrieved from the Web of Science Core Collection. The VOSviewer (v.1.6.19), CiteSpace (v.6.3 R1), R language (v.4.3.2), and Bibliometrix (v.4.1.4) packages (https://www.bibliometrix.org) were used for the bibliometric analysis and visualization. Annual output, author, country, institution, journal, cited literature, co-cited literature, and keywords were also included. The citation frequency and H-index were used to evaluate quality and influence. Results: In total, 1,285 publications in the field of lipid metabolism in CKD were identified in this study. A total of 7,615 authors from 1,885 institutions in 69 countries and regions published articles in 466 journals. Among them, China was the most productive (368 articles), and the United States had the most citations (17,880 times) and the highest H-index (75). Vaziri Nosratola D, Levi Moshe, Fornoni Alessia, Zhao Yingyong, and Merscher Sandra emerged as core authors. Levi Moshe (2,247 times) and Vaziri Nosratola D (1,969 times) were also authors of the top two most cited publications. The International Journal of Molecular Sciences and Kidney International are the most published and cited journals in this field, respectively. Cardiovascular disease (CVD) and diabetic kidney disease (DKD) have attracted significant attention in the field of lipid metabolism. Oxidative stress, inflammation, insulin resistance, autophagy, and cell death are the key research topics in this field. Conclusion: Through bibliometric analysis, the current status and global trends in lipid metabolism in CKD were demonstrated. CVD and DKD are closely associated with the lipid metabolism of patients with CKD. Future studies should focus on effective CKD treatments using lipid-lowering targets.
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ETHNOPHARMACOLOGICAL RELEVANCE: Osteosarcoma (OS) is characterized by rapid growth and frequent pulmonary metastasis. Eurycoma longifolia Jack, a flowering plant primarily found in Southeast Asian countries, is commonly used in traditional herbal medicine. Its root extract is mainly used for against cancer, malaria, parasites and other conditions. The active compound in its root extract, eurycomanone (EUR), has been proven to inhibit lung and liver cancer proliferation. AIM OF THE STUDY: Our research aimed to investigate the inhibitory effect and underlying molecular mechanism of EUR on OS growth and metastasis. MATERIALS AND METHODS: In vitro experiments: western blotting (WB) screened 41 compounds that inhibited GRP78 expression and evaluated the protein levels of GRP78, PARP, cleaved-PARP, MMP2, and MMP9. Cell proliferation was evaluated using CCK-8, EdU, colony formation assay, and cell apoptosis was assessed by flow cytometry. Transwell, wound healing, and tube formation assays were performed to determine the effect of EUR on tumor invasion, migration, and angiogenesis, respectively. Quantitative real-time polymerase chain (qRT-PCR) and dual-luciferase activity assays detected GRP78 mRNA stability and transcription levels post-EUR and thapsigargin treatment. RNA-Seq identified signaling pathways inhibited by EUR. In vivo experiments: effects of EUR in mice were evaluated by H&E staining to detect lung metastasis and potential toxic effects in tissues. Immunohistochemical (IHC) staining detected the expression of Ki-67, CD31, and cleaved caspase-3 in tumors. RESULTS: GRP78 is highly expressed in OS and correlated with poor prognosis. In vitro, eurycomanone (EUR) significantly downregulated GRP78 expression, inhibited cell proliferation, migration, invasion, tube formation, and induced apoptosis. Moreover, it enhanced trichostatin A (TSA) sensitivity and exhibited inhibitory effects on other cancer types. Mechanistically, EUR decreased GRP78 mRNA stability and transcription. In vivo, EUR inhibited proliferation and invasion in tibial and PDX models. CONCLUSIONS: Our study demonstrated that EUR inhibits the growth and metastasis of OS by reducing GRP78 mRNA stability and inhibiting its transcription, which offers a novel approach for clinical treatment of OS.
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Antineoplásicos Fitogênicos , Neoplasias Ósseas , Proliferação de Células , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico , Osteossarcoma , Animais , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Humanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/isolamento & purificação , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB C , Apoptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Movimento Celular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , FemininoRESUMO
BACKGROUND: Camptothecin (CPT) is one of the frequently used small chemotherapy drugs for treating hepatocellular carcinoma (HCC), but its clinical application is limited due to severe toxicities and acquired resistance. Combined chemo-gene therapy has been reported to be an effective strategy for counteracting drug resistance while sensitizing cancer cells to cytotoxic agents. Thus, we hypothesized that combining CPT with miR-145 could synergistically suppress tumor proliferation and enhance anti-tumor activity. METHODS: Lactobionic acid (LA) modified lipid nanoparticles (LNPs) were developed to co-deliver CPT and miR-145 into asialoglycoprotein receptors-expressing HCC in vitro and in vivo. We evaluated the synergetic antitumor effect of miR-145 and CPT using CCK8, Western blotting, apoptosis and wound scratch assay in vitro, and the mechanisms underlying the synergetic antitumor effects were further investigated. Tumor inhibitory efficacy, safety evaluation and MRI-visible ability were assessed using diethylnitrosamine (DEN) + CCl4-induced HCC mouse model. RESULTS: The LA modification improved the targeting delivery of cargos to HCC cells and tissues. The LA-CMGL-mediated co-delivery of miR-145 and CPT is more effective on tumor inhibitory than LA-CPT-L or LA-miR-145-L treatment alone, both in vitro and in vivo, with almost no side effects during the treatment period. Mechanistically, miR-145 likely induces apoptosis by targeting SUMO-specific peptidase 1 (SENP1)-mediated hexokinase (HK2) SUMOylation and glycolysis pathways and, in turn, sensitizing the cancer cells to CPT. In vitro and in vivo tests confirmed that the loaded Gd-DOTA served as an effective T1-weighted contrast agent for noninvasive tumor detection as well as real-time monitoring of drug delivery and biodistribution. CONCLUSIONS: The LA-CMGL-mediated co-delivery of miR-145 and CPT displays a synergistic therapy against HCC. The novel MRI-visible, actively targeted chemo-gene co-delivery system for HCC therapy provides a scientific basis and a useful idea for the development of HCC treatment strategies in the future.
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Camptotecina , Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Nanopartículas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Humanos , Nanopartículas/química , Camptotecina/farmacologia , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Lipídeos/química , LipossomosRESUMO
Resveratrol is a non-flavonoid polyphenolic compound with numerous functional properties, such as anticancer, anti-inflammation, anti-oxidation, anti-obesity and more. However, resveratrol's poor solubility within aqueous media and low stability usually lead to compromised bioavailability, ultimately limiting its uptake and applications. Nanodelivery technologies have been studied intensively due to their potential in effectively improving resveratrol properties, thereby providing promising solutions for enhancing the bioavailability of resveratrol. Thus, this article aimed to review the recent advances of resveratrol nanodelivery systems, specifically on the types of nanodelivery systems, the corresponding preparation principles, advantages, as well as potential limitations associated. Meanwhile, studies have also found that coupled with nanodelivery systems, the functional properties of resveratrol could trigger apoptosis in cancer cells and inflammatory cells through various signaling pathways. Therefore, this article will also lead into discussions on the application aspects of resveratrol nanodelivery systems, emphasizing toward the fields of biomedical and food sciences. Potential pitfalls of resveratrol nanodelivery systems, such as issues with toxicity and target release, as well as outlooks regarding resveratrol nanodelivery systems are included in the Conclusion section, in the hope to provide insights for relevant future research.
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Resveratrol , Resveratrol/química , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Resveratrol/farmacocinética , Humanos , Animais , Sistemas de Liberação de Medicamentos/métodos , Disponibilidade Biológica , Nanopartículas/químicaRESUMO
Lipid homeostasis is crucial for proper cellular and systemic functions. A growing number of studies confirm the importance of lipid homeostasis in diabetic kidney disease (DKD). Lipotoxicity caused by imbalance in renal lipid homeostasis can further exasperate renal injury. Large lipid deposits and lipid droplet accumulation are present in the kidneys of DKD patients. Autophagy plays a critical role in DKD lipid homeostasis and is involved in the regulation of lipid content. Inhibition or reduction of autophagy can lead to lipid accumulation, which in turn further affects autophagy. Lipophagy selectively recognizes and degrades lipids and helps to regulate cellular lipid metabolism and maintain intracellular lipid homeostasis. Therefore, we provide a systematic review of fatty acid, cholesterol, and sphingolipid metabolism, and discuss the responses of different renal intrinsic cells to imbalances in lipid homeostasis. Finally, we discuss the mechanism by which autophagy, especially lipophagy, maintains lipid homeostasis to support the development of new DKD drugs targeting lipid homeostasis.
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Autofagia , Nefropatias Diabéticas , Homeostase , Metabolismo dos Lipídeos , Humanos , Nefropatias Diabéticas/metabolismo , Metabolismo dos Lipídeos/fisiologia , Autofagia/fisiologia , Animais , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Esfingolipídeos/metabolismo , Rim/metabolismoRESUMO
The aim of individuals consuming health supplements is to attain a robust state through nutritional regulation. However, some unscrupulous manufacturers, motivated by profit, fraudulently incorporate drugs or unauthorized components with therapeutic effects into the product for instant product performance enhancement. The long-term use of these products may inadvertently inflict harm on human health and fail to promote nutritive healthcare. The illegal inclusion of these substances is prevalent in kidney-tonifying and sexuality-enhancing products. Developing effective analytical methods to identify these products and screen for illegal added ingredients can effectively prevent such products from reaching and remaining on the market. A target screening method for the detection and quantification of 90 phosphodiesterase type 5 inhibitors (PDE-5is) in 5 kinds of health products was developed and validated. The type of dietary supplements varied from tablets, capsules, and protein powder to wine and beverages. Sample preparation was completed with a one-step liquid phase extraction. The screening process of 90 PDE-5is was done efficiently within 25 min by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using the dynamic multiple reaction monitoring (dMRM) technique. The LODs of 90 PDE-5is were detected at levels ranging from 25 to 85 ng/g or ng/mL. This novel targeting methodology was effective and can be applied to routine market supervision. Among 286 batches of samples, 8 batches were found to be positive. Three kinds of PDE-5is were first detected in healthy products. The screening method demonstrated herein will be a promising and powerful tool for rapid screening of PDE-5is.
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Suplementos Nutricionais , Espectrometria de Massa com Cromatografia Líquida , Inibidores da Fosfodiesterase 5 , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Suplementos Nutricionais/análise , Espectrometria de Massa com Cromatografia Líquida/métodos , Inibidores da Fosfodiesterase 5/análise , Inibidores da Fosfodiesterase 5/química , Espectrometria de Massas em Tandem/métodosRESUMO
Oat products have gained widespread recognition as a health food due to their rich and balanced nutritional profile and convenience. However, the unique matrix composition of oats, which differs significantly from other cereals, presents specific challenges for mycotoxin analysis. This study presents an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method enhanced with an innovative egg white gel pretreatment for the simultaneous analysis of 13 regulated and unregulated trichothecenes in oats. The method demonstrated excellent performance with high accuracy (> 87.5%), repeatability (< 5.7%), and reproducibility (< 8.1%). Analysis of 100 commercial oat products revealed a concerning detection rate (78%) for at least one of the 11 trichothecenes investigated. Notably, deoxynivalenol, exceeding the standard limit in 2% of samples, exhibited the highest detection rate (62%). Additionally, concerning co-occurrence patterns and positive correlations were observed, highlighting potential synergistic effects. The first-time detection of unregulated mycotoxins (T-2 triol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, and neosolaniol) underscores the need for comprehensive monitoring. This method, while developed for oats, shows potential for broader application to other cereals, though further investigation and confirmation are necessary. These findings suggest a potentially underestimated risk of trichothecenes in oats, necessitating continuous monitoring to ensure consumer safety.
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Avena , Contaminação de Alimentos , Limite de Detecção , Espectrometria de Massas em Tandem , Tricotecenos , Avena/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Tricotecenos/análise , Contaminação de Alimentos/análise , Géis/química , Reprodutibilidade dos TestesRESUMO
The conventional covalent organic framework (COF)-based electrolytes with tailored ionic conducting behaviors are typically fabricated in the powder morphology, requiring further compaction procedures to operate as solid electrolyte tablets, which hinders the large-scale manufacturing of COF materials. In this study, we present a feasible electrospinning strategy to prepare scalable, self-supporting COF membranes (COMs) that feature a rigid COF skeleton bonded with flexible, lithiophilic polyethylene glycol (PEG) chains, forming an ion conduction network for Li⺠transport. The resulting PEG-COM electrolytes exhibit enhanced dendrite inhibition and high ionic conductivity of 0.153 mS cm⻹ at 30 °C. The improved Li⺠conduction in PEG-COM electrolytes stems from the loose ion pairing in the structure and the production of higher free Li⺠content, as confirmed by solid-state 7Li NMR experiments. These changes in the local microenvironment of Li⺠facilitate its directional movement within the COM pores. Consequently, solid-state symmetrical Li|Li, Li|LFP, and pouch cells demonstrate excellent electrochemical performance at 60 °C. This strategy offers a universal approach for constructing scalable COM-based electrolytes, thereby broadening the practical applications of COFs in solid-state lithium metal batteries.
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Urushiol-induced allergic contact dermatitis (ACD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to pruritus and eczematous lesions. ACD is triggered by immune imbalance. Aloe emodin is an anthraquinone derivative extracted from rhubarb, aloe and other traditional Chinese medicines. It has a wide range of pharmacological effects, including anti-inflammatory, anti-tumor, and anti-allergic effects. The purpose of our study was to demonstrate the effectiveness of aloe-emodin on urushiol-induced acute pruritus and allergic contact dermatitis. The results showed that urushiol could stimulate keratinocytes to release chemokines CXCL1, CXCL2, CCL2, TSLP, and TNF-α, which recruit or activate mast cells. Aloe-emodin treatment inhibited inflammatory-response-induced mast cell degranulation in skin lesions and suppressed the expression of inflammatory cytokines, such as interleukin-4, and interleukin-6. Therefore, the results indicate that aloe-emodin can improve urushiol-induced acute pruritus and allergic contact dermatitis in mice by inhibiting mast cell degranulation.
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BACKGROUND: Silicosis is an irreversible fibrotic disease of the lung caused by chronic exposure to silica dust, which manifests as infiltration of inflammatory cells, excessive secretion of pro-inflammatory cytokines, and pulmonary diffuse fibrosis. As the disease progresses, lung function further deteriorates, leading to poorer quality of life of patients. Currently, few effective drugs are available for the treatment of silicosis. Bicyclol (BIC) is a compound widely employed to treat chronic viral hepatitis and drug-induced liver injury. While recent studies have demonstrated anti-fibrosis effects of BIC on multiple organs, including liver, lung, and kidney, its therapeutic benefit against silicosis remains unclear. In this study, we established a rat model of silicosis, with the aim of evaluating the potential therapeutic effects of BIC. METHODS: We constructed a silicotic rat model and administered BIC after injury. The FlexiVent instrument with a forced oscillation system was used to detect the pulmonary function of rats. HE and Masson staining were used to assess the effect of BIC on silica-induced rats. Macrophages-inflammatory model of RAW264.7 cells, fibroblast-myofibroblast transition (FMT) model of NIH-3T3 cells, and epithelial-mesenchymal transition (EMT) model of TC-1 cells were established in vitro. And the levels of inflammatory mediators and fibrosis-related proteins were evaluated in vivo and in vitro after BIC treatment by Western Blot analysis, RT-PCR, ELISA, and flow cytometry experiments. RESULTS: BIC significantly improved static compliance of lung and expiratory and inspiratory capacity of silica-induced rats. Moreover, BIC reduced number of inflammatory cells and cytokines as well as collagen deposition in lungs, leading to delayed fibrosis progression in the silicosis rat model. Further exploration of the underlying molecular mechanisms revealed that BIC suppressed the activation, polarization, and apoptosis of RAW264.7 macrophages induced by SiO2. Additionally, BIC inhibited SiO2-mediated secretion of the inflammatory cytokines IL-1ß, IL-6, TNF-α, and TGF-ß1 in macrophages. BIC inhibited FMT of NIH-3T3 as well as EMT of TC-1 in the in vitro silicosis model, resulting in reduced proliferation and migration capability of NIH-3T3 cells. Further investigation of the cytokines secreted by macrophages revealed suppression of both FMT and EMT by BIC through targeting of TGF-ß1. Notably, BIC blocked the activation of JAK2/STAT3 in NIH-3T3 cells required for FMT while preventing both phosphorylation and nuclear translocation of SMAD2/3 in TC-1 cells necessary for the EMT process. CONCLUSION: The collective data suggest that BIC prevents both FMT and EMT processes, in turn, reducing aberrant collagen deposition. Our findings demonstrate for the first time that BIC ameliorates inflammatory cytokine secretion, in particular, TGF-ß1, and consequently inhibits FMT and EMT via TGF-ß1 canonical and non-canonical pathways, ultimately resulting in reduction of aberrant collagen deposition and slower progression of silicosis, supporting its potential as a novel therapeutic agent.
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Fibrose Pulmonar , Transdução de Sinais , Silicose , Fator de Crescimento Transformador beta1 , Animais , Silicose/tratamento farmacológico , Silicose/patologia , Silicose/metabolismo , Silicose/complicações , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Fibrose Pulmonar/complicações , Camundongos , Transdução de Sinais/efeitos dos fármacos , Células RAW 264.7 , Masculino , Fator de Crescimento Transformador beta1/metabolismo , Células NIH 3T3 , Ratos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pulmão/patologia , Pulmão/efeitos dos fármacos , Citocinas/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Inflamação/patologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Compostos de BifeniloRESUMO
Background: Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored. Purpose: The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice. Methods: In vivo: 3.5% DSS-induced experimental colitis mice were treated with BTW (Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro: Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels. Results: BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway. Conclusion: BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
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PURPOSE: Resolvin D1 (RvD1) inhibits inflammation, reduces oxidative stress, and forecasts the risk of cardiovascular events, but relevant evidence in hemodialysis patients is lacking. This study intended to investigate the predictive value of RvD1 for major adverse cardiovascular events (MACE) risk in hemodialysis patients. METHODS: Totally, 252 patients who underwent hemodialysis were included. Serum RvD1 was measured by enzyme-linked immunosorbent assay. Patients were followed up with a median of 12.1 months. MACE was recorded during the follow-up period. RESULTS: RvD1 was inversely correlated with diabetes history (P = 0.002), cardiac troponin T (TnT) (P = 0.029), and high sensitivity C-reactive protein (hsCRP) (P < 0.001) in hemodialysis patients. 25 hemodialysis patients experienced MACE. RvD1 was reduced in hemodialysis patients with MACE versus those without MACE (P = 0.004). RvD1 exhibited a certain value in forecasting MACE risk, with an area under curve (AUC) of 0.675 [95% confidence interval CI: 0.565-0.786]. Increased RvD1 cut by median (P = 0.043) and cut by quartile (P = 0.042) were related to decreased accumulating MACE in hemodialysis patients. Moreover, RvD1 independently predicted declined MACE risk [odds ratio (OR) = 0.644, P = 0.045], but age (OR = 1.048, P = 0.039) and TnT (OR = 1.006, P = 0.005) independently predicted ascended MACE risk in hemodialysis patients. The combination of these independent factors displayed a good value for estimating MACE risk in hemodialysis patients with an AUC of 0.744 (95% CI: 0.640-0.849). CONCLUSION: Serum RvD1 is inversely correlated with diabetes history, TnT, and hsCRP in hemodialysis patients. More importantly, it could serve as a potential marker to predict MACE risk in these patients.
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Ru-based pyrochlores (e.g., Y2Ru2O7-d) are promised to replace IrO2 in polymer electrolyte membrane (PEM) electrolyzers. It is significant to reveal the cliff attenuation on the oxygen evolution reaction (OER) performance of these pyrochlores. In this work, we monitor the structure changes and electrochemical behavior of Y2Ru2O7-d over the OER process, and it is found that the reason of decisive OER inactivation is derived from an insulator transition occurred within Y2Ru2O7-d due to its inner ²perfecting² lattice induced by continuous atom rearrangement. Therefore, a stabilization strategy of the Ir-substituted Y2Ru2O7-d is proposed to alleviate this undesirable behavior. The double-exchange interaction between Ru and Ir in [RuO6] and [IrO6] octahedra leads the charge redistribution with simultaneous spin configuration adjustment. The electronic state in newly formed octahedrons centered with Ru 4d3 (with the state of eg'2--a1g-1 eg0) and Ir 5d6 (eg'4a1g-2 eg0) relieves the uneven electron distributions in [RuO6] orbital. The attenuated Jahn-Teller effect alleviates atom rearrangement, represented as the mitigation of insulator transition, surface reconstruction, and metal dissolution. As results, the Ir-substituted Y2Ru2O7-d presents the greatly improved OER stability and PEM durability. This study unveils the OER degradation mechanism and stabilization strategy for material design of Ru-based OER catalysts for electrochemical applications.
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Introduction: Healthcare is essential for asthma control, however, whether family-supported healthcare improves therapeutic effects in childhood asthma remains unclear. Methods: The enrolled patients were randomly divided into control and intervention groups. The pulmonary function was evaluated by forced expiratory volume in 1 s as a percentage of forced vital capacity (FEV1/FVC) and fractional exhaled nitric oxide (FeNO). Asthma control and life quality were assessed via a childhood asthma control test and pediatric asthma quality of life questionnaire. Inflammatory cytokines interleukin-6 (IL-6) and interleukin-17 (IL-17) were determined by enzyme-linked immunosorbent assay. Results: No significant differences existed in the basic characteristics of asthma children and their parents among two groups. The increase of FEV1/FVC was higher in the intervention group versus the control group (76.47 ± 10.76% vs 69.76 ± 8.88%, p = 0.001 at the time of post-intervention), and the decrease of FeNO was greater in the intervention group (30.43 ± 6.85 bbp vs 35.64 ± 6.62 bbp, p = 0.003 at the time of post-intervention). Family-supported healthcare highly improved asthma control and quality of life in childhood asthma post-treatment. Meanwhile, the inflammatory cytokines IL-17 (118.14 ± 25.79 pg/mL in intervention group vs 142.86 ± 28.68 pg/mL in control group, p = 0.004 at the time of post-intervention) and IL-6 (103.76 ± 23.11 pg/mL in intervention group vs 119.73 ± 22.68 pg/mL in control group, p = 0.009 at the time of post-intervention) significantly decreased by family-supported healthcare intervention. Importantly, acute exacerbation (80.8% in intervention group vs 95.7% in control group, p = 0.030) and rehospitalization cases (88.5% in intervention group vs 100% in control group, p = 0.028) also decreased by family-supported healthcare intervention. Discussion: Family-supported healthcare improves pulmonary function and quality of life while alleviates inflammation, acute exacerbation, and rehospitalization in childhood asthma post-routine treatment.
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The occurrence of myocardial ischemia/reperfusion injury is commonly observed during cardiac surgery; however, there remains a dearth of effective therapeutic strategies to mitigate this injury. The a disintegrin and metallopeptidase domain 10 (ADAM10) is a transmembrane protein anchored on the cell membrane surface, and its precise mechanism of action in myocardial ischemia/reperfusion injury remains incompletely understood. This study aims to investigate the impact of ADAM10 on cardiomyocyte injury induced by hypoxia/reoxygenation (H/R) and elucidate the underlying mechanisms. The ADAM10 overexpression plasmid was transfected into H9c2 cells, which were subsequently treated with the Notch signaling pathway inhibitor DAPT and cultured under H/R conditions. Cell proliferation activity was assessed using the CCK-8 assay. The levels of LDH, SOD, and MDA were quantified through colorimetric analysis. The levels of ROS and the rate of apoptosis were measured using flow cytometry. The morphological changes in the nucleus of H9c2 cells were observed by employing Hoechst 33258 staining. The mRNA expression levels of ADAM10, Notch1, NICD, and Hes1 in H9c2 cells were determined using qRT-PCR. The expressions of Notch signaling pathway and apoptosis-related proteins were analyzed by Western blot. Overexpression of ADAM10 provided protection to H9c2 cells against injury induced by H/R, leading to an increase in SOD levels and alleviation of oxidative stress caused by the accumulation of ROS and the decrease of SOD activity. Meanwhile, overexpression of ADAM10 inhibited apoptosis in H9c2 cells exposed to H/R by regulating the expression of apoptosis-related proteins, such as Bax, Bcl-2 and Cleaved-caspase-3. Additionally, overexpression of ADAM10 facilitated the activation of the Notch1 signaling pathway in H9c2 cells exposed to H/R by upregulating the protein expression of Notch1, NICD, and Hes1. However, the protective effect of ADAM10 on H/R-induced H9c2 cells was partially reversed by DAPT. Our findings demonstrate that ADAM10 exerts protective effects in H/R-induced H9c2 cells by suppressing oxidative stress and apoptosis via the activation of the Notch signaling pathway.
Assuntos
Proteína ADAM10 , Secretases da Proteína Precursora do Amiloide , Apoptose , Hipóxia Celular , Proteínas de Membrana , Miócitos Cardíacos , Transdução de Sinais , Fatores de Transcrição HES-1 , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/patologia , Animais , Ratos , Linhagem Celular , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Fatores de Transcrição HES-1/metabolismo , Fatores de Transcrição HES-1/genética , Receptores Notch/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genética , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células , Dipeptídeos/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Estresse Oxidativo , Diaminas/farmacologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genéticaRESUMO
In recent years, ozone (O3) has emerged as the primary air pollutant in China, superseding PM2.5. Previous studies have concentrated on the spatiotemporal variation of ozone pollution, the analysis of its sources and drivers, as well as its environmental impacts and health benefits. Since ozone pollution can be dynamically transferred through industrial activities and meteorological factors, it is crucial to scientifically identify the spatial spillover and path-dependent effects of ozone pollution in China. However, existing studies have not yet addressed this issue. Therefore, we investigate the spatiotemporal evolution and the spatial spillover of ozone pollution by means of the exploratory spatial data analysis (ESDA) using panel data of 30 Chinese provinces from 2013 to 2020 in this study. The dynamic spatial Durbin model (SDM) was employed to reveal the key drivers of ozone pollution from the perspectives of spatial spillover and path-dependence effects. The direct and spillover effects of each driver on ozone pollution are systematically analyzed. The results show that from 2013 to 2020 ozone concentrations followed a fluctuating upward trend at national and provincial scales. Ozone pollution presented significant spatial spillover and path dependence effects. The direct effects indicated that economic growth, technological level, industrial structure, energy structure, ventilation coefficient, relative humidity and precipitation were the key drivers of local ozone pollution. The spillover effects indicated that population density, technology level, industrial structure, environmental regulations, ventilation coefficient, sunshine hours and relative humidity had significant spatial spillover effects on ozone pollution of surrounding regions. These findings will contribute to the understanding of the spatial spillover and path-dependent effects of O3 pollution, and provide scientific guidance for regional synergy and long-term ozone control policies in China.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Ozônio , Análise Espaço-Temporal , Ozônio/análise , China , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricosRESUMO
Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment and functional loss in elderly patients. Progressive remodeling of cerebral microvessels due to arterial hypertension or other vascular risk factors, such as aging, can cause dementia or stroke. Typical imaging characteristics of CSVD include cerebral microbleeds (CMB), brain atrophy, small subcortical infarctions, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). Nevertheless, no animal models that reflect all the different aspects of CSVD have been identified. Here, we generated a new CSVD animal model using D-galactose (D-gal) combined with cerebral hypoperfusion in spontaneously hypertensive rats (SHR), which showed all the hallmark pathological features of CSVD and was based on vascular risk factors. SHR were hypodermically injected with D-gal (400 mg/kg/d) and underwent modified microcoil bilateral common carotid artery stenosis surgery. Subsequently, neurological assessments and behavioral tests were performed, followed by vascular ultrasonography, electron microscopy, flow cytometry, and histological analyses. Our rat model showed multiple cerebrovascular pathologies, such as CMB, brain atrophy, subcortical small infarction, WMH, and EPVS, as well as the underlying causes of CSVD pathology, including oxidative stress injury, decreased cerebral blood flow, structural and functional damage to endothelial cells, increased blood-brain barrier permeability, and inflammation. The use of this animal model will help identify new therapeutic targets and subsequently aid the development and testing of novel therapeutic interventions. Main process of the study: Firstly, we screened for optimal conditions for mimicking aging by injecting D-gal into rats for 4 and 8 weeks. Subsequently, we performed modified microcoil BCAS intervention for 4 and 8 weeks in rats to screen for optimal hypoperfusion conditions. Finally, based on these results, we combined D-gal for 8 weeks and modified microcoil BCAS for 4 weeks to explore the changes in SHR.
Assuntos
Envelhecimento , Doenças de Pequenos Vasos Cerebrais , Modelos Animais de Doenças , Galactose , Hipertensão , Ratos Endogâmicos SHR , Animais , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Envelhecimento/patologia , Masculino , Ratos , Hipertensão/complicações , Fatores de Risco , Circulação Cerebrovascular , Encéfalo/patologia , Encéfalo/diagnóstico por imagemRESUMO
Naturally occurring substances and their derivatives function as vital resources for pesticides that can be used in fields, such as insecticide production and fungicide development. As a botanical entity displaying multifaceted biological functions, wormwood has received thorough scrutiny across multiple sectors. The insect repellency potency combined with antibacterial and antifungal activities of wormwood position it as a potential candidate for prospective development into eco-friendly chemical pesticides. In this research, Wormwood essential oil was procured via ethanol water under ultrasonic scenarios and subsequently diluted with PEG 400 to formulate green chemical pesticides. The defensive efficacy of this green pesticide on plants was validated through 2 weeks of clustered plant growth experiments. Active constituents that exerted their effects were scrutinized by GC-MS. Furthermore, this green pesticide also displays efficacious effects on the prevention and management of aphids, exhibiting a dose-dependent relationship. 4-terpenol, eucalyptol, carvacrol, and L-borneol were identified by GC-MS as the predominant active constituents in this green chemical pesticide. Wormwood can be leveraged to develop green chemical pesticides, which can protect plants without contaminating the environment.