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Psoriasis is considered to be multifactorial, with both genetic and environmental factors contributing to its development. Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment, originating from sources such as cigarette smoke, exhaust emissions, grilled foods, smoked foods and urban air. Researchs have established a link between PAHs exposure and autoimmune disorders; however, specific effects of PAHs on psoriasis remain underexplored. This study aims to evaluate the correlation between PAHs exposure and susceptibility to psoriasis. We analysed eight monohydroxy PAHs (1-Hydroxynaphthalene (1-NAP), 2-Hydroxynaphthalene (2-NAP), 3-Hydroxyfluorene (3-FLU), 2-Hydroxyfluorene (2-FLU), 1-Hydroxyphenanthrene (1-PHE), 1-Hydroxypyrene (1-PYR), 2-Hydroxyphenanthrene (2-PHE) and 3-Hydroxyphenanthrene (3-PHE)) in 5996 participants from the National Health and Nutrition Examination Survey (NHANES). We employed multivariate logistic regression, trend analysis, weighted quantile sum (WQS) regression and restricted cubic spline (RCS) analysis to investigate the relationship between PAHs exposure and psoriasis risk. Multivariate logistic regression and trend analysis revealed that monohydroxy PAHs, including 2-NAP, 3-FLU, 2-FLU and the mixture of 2-PHE and 3-PHE, are associated with an increased risk of psoriasis. Additionally, WQS regression showed a significant positive correlation between combined exposure to monohydroxy PAHs and psoriasis risk, with the mixture of 2-PHE and 3-PHE (47.3%) being the most influential factor. RCS regression further corroborated these findings. Specifically, 2-FLU can increase the expression of psoriasis-related inflammatory factors in HaCaT cells. In conclusion, PAHs exposure increases the risk of developing psoriasis. Efforts to reduce PAHs levels in the environment and minimise exposure are crucial for public health strategies aimed at preventing psoriasis.
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Hidrocarburos Policíclicos Aromáticos , Psoriasis , Humanos , Psoriasis/inducido químicamente , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Exposición a Riesgos Ambientales/efectos adversos , Encuestas Nutricionales , Factores de Riesgo , Modelos LogísticosRESUMEN
The recently discovered complete ammonia oxidation (comammox Nitrospira) containing clade A and clade B has further complemented our understanding of nitrification process. Nevertheless, understanding the community feature of comammox Nitrospira clades A and B and their relative contribution to nitrification in paddy rhizosphere are still in its infancy. In this study, we assessed the community diversity and structure of comammox Nitrospira clades A and B in paddy rhizosphere and bulk soils under thirty years of different fertilization strategies, i.e., non-fertilization control (CK), chemical fertilizers application (NPK), and NPK plus swine manure (NPKM), respectively. NPKM significantly increased the a-diversity (Chao1 and Shannon indices) of comammox Nitrospira clade A and altered the community structure (P < 0.05) but had little effect on clade B. A two-way analysis of variance (ANOVA) showed that the effect of long-term fertilization on soil comammox Nitrospira community and nitrification potential rate (PNR) was much greater than that of rhizosphere. Compared with NPK, soil PNR was greatly increased by 51.0% under the NPKM treatment in the rhizosphere (P < 0.05). Phylogenetic analysis showed that NPKM improved the relative abundances of sub-clade A.2.1 and sub-clade A.3.2 of the comammox clade A community, with an average increase of 212.2 and 210.4% in both rhizosphere and bulk soils relative to the NPK treatment. Soil organic matter, NH4+-N, and pH were significant soil drivers of comammox Nitrospira clades A and B community. Furthermore, linear regression and structural equation modeling clearly showed that comammox Nitrospira clade A a-diversity were significantly associated with soil PNR (P < 0.05). Our results suggest (i) that comammox Nitrospira clade A are sensitive to the organic fertilization; and (ii) that comammox Nitrospira clade A contribute more to nitrification than clade B under the long-term organic fertilized paddy soil.
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Fertilizantes , Nitrificación , Rizosfera , Microbiología del Suelo , Suelo , Fertilizantes/análisis , China , Suelo/química , Filogenia , Amoníaco/metabolismo , OryzaRESUMEN
The objective of this study was to elucidate the protective role of quercetin in atherosclerosis by examining its effect on the phenotypic switch of vascular smooth muscle cells (VSMCs) to macrophage-like cells and the underlying regulatory pathways. Aorta tissues from apolipoprotein E-deficient (ApoE KO) mice fed a high-fat diet (HFD), treated with or without 100 mg/kg/day quercetin, were analyzed for histopathological changes and molecular mechanisms. Quercetin was found to decrease the size of atherosclerotic lesions and mitigate lipid accumulation induced by HFD. Fluorescence co-localization analysis revealed a higher presence of macrophage-like vascular smooth muscle cells (VSMCs) co-localizing with phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 3 (p-STAT3), and Krüppel-like factor 4 (KLF4) in regions of foam cell aggregation within aortic plaques. However, this co-localization was reduced following treatment with quercetin. Quercetin treatment effectively inhibited the KLF4-mediated phenotypic switch in oxidized low-density lipoprotein (ox-LDL)-loaded mouse aortic vascular smooth muscle cells (MOVAS), as indicated by decreased expressions of KLF4, LGALS3, CD68, and F4/80, increased expression of alpha smooth muscle actin (α-SMA), reduced intracellular fluorescence Dil-ox-LDL uptake, and decreased lipid accumulation. In contrast, APTO-253, a KLF4 activator, was found to reverse the effects of quercetin. Furthermore, AG490, a JAK2 inhibitor, effectively counteracted the ox-LDL-induced JAK2/STAT3 pathway-dependent switch to a macrophage-like phenotype and lipid accumulation in MOVAS cells. These effects were significantly mitigated by quercetin but exacerbated by coumermycin A1, a JAK2 activator. Our research illustrates that quercetin inhibits the KLF4-mediated phenotypic switch of VSMCs to macrophage-like cells and reduces atherosclerosis by suppressing the JAK2/STAT3 pathway.
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Aterosclerosis , Macrófagos , Músculo Liso Vascular , Miocitos del Músculo Liso , Quercetina , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Masculino , Ratones , Aorta/metabolismo , Aorta/efectos de los fármacos , Aorta/patología , Apolipoproteínas E/metabolismo , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Dieta Alta en Grasa/efectos adversos , Janus Quinasa 2/metabolismo , Factor 4 Similar a Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Fenotipo , Quercetina/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismoRESUMEN
AIMS: This study aimed to elucidate the biological roles and regulatory mechanisms of B-cell lymphoma 7 protein family member A (BCL7A) in acute myeloid leukemia (AML), particularly its interaction with polypyrimidine tract binding protein 1 (PTBP1) and the effects on cancer progression and drug resistance. METHODS: BCL7A expression levels were analyzed in AML tissues and cell lines, focusing on associations with promoter hypermethylation. Interaction with PTBP1 and effects of differential expression of BCL7A were examined in vitro and in vivo. The impacts on cell proliferation, cycle progression, apoptosis, and differentiation were studied. Additionally, the regulatory roles of BCL7A on interferon regulatory factor 7 (IRF7) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) were assessed. RESULTS: BCL7A was downregulated in AML due to promoter hypermethylation and negatively regulated by PTBP1. Upregulation of BCL7A impeded AML cell growth, induced apoptosis, promoted cell differentiation, and decreased cell infiltration into lymph nodes, enhancing survival in mouse models. Overexpression of BCL7A upregulated IRF7 and downregulated HMGCS1, linking to reduced AML cell malignancy and decreased resistance to cytarabine. CONCLUSIONS: BCL7A acts as a tumor suppressor in AML, inhibiting malignant progression and enhancing drug sensitivity through the IRF7/HMGCS1 pathway. These findings suggest potential therapeutic targets for improving AML treatment outcomes.
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Apoptosis , Proliferación Celular , Resistencia a Antineoplásicos , Ribonucleoproteínas Nucleares Heterogéneas , Leucemia Mieloide Aguda , Proteína de Unión al Tracto de Polipirimidina , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Ratones , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Proteína de Unión al Tracto de Polipirimidina/genética , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , Metilación de ADN , Regiones Promotoras Genéticas , Progresión de la Enfermedad , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Femenino , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Diferenciación Celular/efectos de los fármacos , Regulación Leucémica de la Expresión Génica/efectos de los fármacosRESUMEN
BACKGROUND: There is increasing evidence suggesting that serum neurofilament light chain (sNfL) levels can be used as biomarkers for axonal injury. Retinol is recognized for its significant involvement in nervous system function, but the precise connection between dietary retinol and sNfL levels remains uncertain. OBJECTIVE: Our objective was to investigate the relationship between dietary retinol intake and sNfL, and to find an optimal retinol intake level for neurological health. METHODS: In the National Health and Nutrition Examination Survey (NHANES), conducted from 2013 to 2014, a cohort of 1684 participants who met the criteria were selected for the study. sNfL levels were measured from stored serum samples using a novel high-throughput immunoassay platform from Siemens Healthineers. Assessment of dietary retinol intake was performed by a uniformly trained interviewer through a 24 h dietary recall method. A generalized linear model was evaluated to assess the correlation between dietary retinol intake and sNfL concentrations. Furthermore, the nonlinear association between the two is further explored using restricted cubic spline (RCS) analysis. RESULTS: Upon adjusting for potential confounders, a 10% increase in dietary retinol intake was associated with a 3.47% increase in sNfL levels (95% CI: 0.54%, 6.49%) across all participants. This relationship was more pronounced in specific subgroups, including those under 60 years of age, non-obese, impaired estimated glomerular filtration rate (eGFR), and non-diabetic. In subgroup analysis, among those younger than 60 years of age (percent change: 3.80%; 95% CI: 0.43%, 7.28%), changes were found in non-obese participants (percent change: 6.28%; 95% CI: 2.66%, 10.02%), those with impaired eGFR (percent change: 6.90%; 95% CI: 1.44%, 12.65%), and non-diabetic patients (percentage change: 4.17%; 95% CI: 1.08%, 7.36%). RCS analysis showed a linear relationship between dietary retinol intake and sNfL levels. Furthermore, the positive correlation between the two was more significant after the inflection point, according to piecewise linear analysis. CONCLUSION: This current investigation uncovered a J-shaped relationship between dietary retinol and sNfL levels, suggesting that axonal damage can occur when dietary retinol intake increases more than a specific threshold. These findings need to be further confirmed in future prospective studies to determine the precise intake level that may trigger axonal injury.
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Biomarcadores , Proteínas de Neurofilamentos , Encuestas Nutricionales , Vitamina A , Humanos , Masculino , Femenino , Persona de Mediana Edad , Proteínas de Neurofilamentos/sangre , Vitamina A/sangre , Vitamina A/administración & dosificación , Adulto , Biomarcadores/sangre , Dieta/métodos , Anciano , Estados Unidos , Estudios TransversalesRESUMEN
Groundwater salinization, a major eco-environmental problem in arid and semi-arid areas, can accelerate soil salinization, reducing crop productivity and imbalances in ecosystem diversity. This study classified water samples collected from the Ulansuhai Lake basin into five clusters using self-organizing maps (SOM). On this basis, multiple isotopes (δ18Owater, δD, 87Sr/86Sr, δ18Osulfate and δ34S) and isotopic models (Rayleigh fractionation and Bayesian isotope mixing models) were used to identify and quantify the genesis and evolution of groundwater salinization. The results showed that the samples were brackish or saline water, and the hydrochemical types were dominated by Na + K-Cl (SO4). It has been proved that the processes associated with groundwater salinization in the Ulansuhai Lake basin were dominated by water-rock interaction and human inputs. Among them, evaporite dissolution contributed substantially to groundwater salinity. Furthermore, salt inputs from human activities cannot be negligible. Based on the model calculations, evaporite dissolution accounted for the most significant proportion of all sources, with a mean value of 53 %. In addition, human inputs from regular agricultural activities (28 % from sewage and manure and 8 % from fertilizers) constituted another vital source of groundwater salinization associated with extensive agricultural activities in the study area. This study's results can deepen our understanding of the genesis of groundwater salinization and the evolution of the agricultural drainage lake basin. This knowledge will assist the Environmental Protection Department in developing effective policies for groundwater management in the Yellow River Basin.
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Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcγ receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by Group A Streptococcus and ImpA secreted by Pseudomonas aeruginosa, as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers αVß3 on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using pre-loading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EV-based cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation.
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Vesículas Extracelulares , Fagocitosis , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Fagocitosis/inmunología , Humanos , Animales , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/metabolismo , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/inmunología , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/inmunología , Pseudomonas aeruginosa/inmunologíaRESUMEN
Free radical damage and oxidative stress are thought to play a crucial role in the development of neurodegenerative diseases. Walnut peptides, especially walnut oligopeptides, have been shown to protect nerve cells from oxidative stress and inflammatory damage, as well as improve memory function. In this study, walnut peptides were obtained from walnut meal through enzymatic hydrolysis, ultrafiltration, and gel filtration chromatography. A novel oligopeptide called AQ was successfully isolated and its chemical structure was identified as AASCDQ using ESI-MS/MS. AQ demonstrated remarkable scavenging activity against O2- free radicals (81.00%), DPPH free radicals (79.40%), and ABTS free radicals (67.09%) at a concentration of 1 mg mL-1. Furthermore, AQ exhibited strong neuroprotective effects against hydrogen peroxide-induced damage in SH-SY5Y cells, reducing cell injury and apoptosis. AQ also effectively inhibited the secretion of pro-inflammatory factors NO (IC50 = 46.03 ± 0.32 µM) and suppressed the expression of IL-6 and TNF-α in RAW264.7 cells stimulated by LPS. In vivo experiments demonstrated that AQ promoted angiogenesis in the quail chick chorioallantoic membrane assay and reduced ROS accumulation in Caenorhabditis elegans, thereby extending its lifespan. The anti-inflammatory mechanism of AQ was further confirmed by western blotting. In summary, the novel oligopeptide AQ possesses potential neuroprotective effects, including antioxidant, anti-inflammatory, angiogenic, and anti-aging properties, making it a promising candidate for the development of functional foods and pharmaceutical products.
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Caenorhabditis elegans , Juglans , Fármacos Neuroprotectores , Oligopéptidos , Animales , Juglans/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Ratones , Caenorhabditis elegans/efectos de los fármacos , Células RAW 264.7 , Humanos , Oligopéptidos/farmacología , Oligopéptidos/química , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Especies Reactivas de Oxígeno/metabolismo , Nueces/química , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
BACKGROUND: Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus.1 We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC. METHODS: CLRS for six patients with CSC was performed from January 2021 to January 2022. We demonstrated the detailed skills of parametrial management during CLRS for CSC in case 5 by means of a video. A 58-year-old woman diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1 CSC received CLRS through five operative ports (Fig. 1). RESULTS: The magnetic resonance imaging (MRI) scans and gross appearance of the specimen are shown in Fig. 2. The median age and body mass index (BMI) of the six patients were 53 years and 23.8, respectively. The median blood loss was 275 mL; the median time of operation was 218 min; the median length of hospitalization was 15 days; and the median time to recover urinary function was 12 days. One patient underwent postoperative radiation for pathologically proven adenocarcinoma with deep stromal invasion,2 while the other five did not. After a median follow-up of 24 months, no patients experienced complications, recurrence, or death (Table 1). CONCLUSIONS: This study details the skills of CLRS for CSC, especially space development and the 'no-look, no-touch' tumor-free principle. It is helpful for clinicians to perform safe and standardized surgery on patients with early-stage CSC. Fig. 1 Trocar placement of complete laparoscopic type C2 radical surgery for early-stage CSC. CSC cervical stump cancer, S superior, I inferior, R right, L left, U umbilicus Fig. 2 MRI scans and gross appearance of the specimen for case 5 with CSC at FIGO 2018 stage IIA1. The tumor lesion on the cervical stump is indicated by yellow arrows. a Axial T2-weighted image; b DKI image; c ADC map; d sagittal T2-weighted image; e sagittal T1-weighted image; f gross appearance of the surgical specimen. MRI magnetic resonance imaging, CSC cervical stump cancer, FIGO International Federation of Gynecology and Obstetrics, DKI diffusional kurtosis imaging, ADC apparent diffusion coefficient Table 1 Clinicopathological characteristics, operative details, and outcomes of patients with cervical stump cancer Patient no. Age at diagnosis (years) BMI Reasons for subtotal hysterectomy FIGO 2018 stage Histology Operation Operation time (mins) Blood loss (mL) Urinary catheter (days) Hospital stay (days) Complications Depth of invasion LVSI LNs dissected TNM stage Tumor size (mm) Postoperative radiotherapy Follow-up (months) Recurrence Death 1 50 25.9 Uterine myoma IIA1 ASC CLRS+PLND 221 360 10 12 No Middle one-third N 13 T2a1N0M0 16 No 30 No No 2 55 17.3 Uterine myoma IB1 AC CLRS+PLND 191 270 20 12 No Deep one-third N 24 T1b1N0M0 10 Yes 20 No No 3 50 24.8 Uterine myoma IB1 SC CLRS+PLND 295 310 13 15 No Superficial one-third N 21 T1b1N0M0 15 No 25 No No 4 63 30.1 Uterine myoma IB1 SC CLRS+PLND 213 180 6 16 No Superficial one-third N 25 T1b1N0M0 15 No 19 No No 5 58 20.2 Postpartum hemorrhage IIA1 SC CLRS+PLND 220 100 11 14 No Middle one-third N 21 T2a1N0M0 15 No 24 No No 6 46 22.7 Uterine myoma IB1 SC CLRS+PLND 215 120 14 17 No Superficial one-third N 26 T1b1N0M0 12 No 23 No No BMI body mass index, FIGO International Federation of Gynecology and Obstetrics, ASC cervical adenosquamous carcinoma, AC cervical adenocarcinoma, SC cervical squamous carcinoma, CLRS+PLND complete laparoscopic radical surgery and pelvic node dissections, LVSI lymphovascular space invasion, N negative, LNs lymph nodes, TNM tumor node metastasis.
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Laparoscopía , Neoplasias del Cuello Uterino , Humanos , Femenino , Laparoscopía/métodos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Pronóstico , Estudios de Seguimiento , Histerectomía/métodos , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Neoplasia Residual/cirugía , Neoplasia Residual/patologíaRESUMEN
Histone lysine lactylation (Kla) has emerged as a distinct epigenetic modification that differs markedly from established acylation modifications through the unique addition of a lactyl group to a lysine residue. Such modifications not only alter nucleosome structure but also significantly impact chromatin dynamics and gene expression, thus playing a crucial role in cellular metabolism, inflammatory responses, and embryonic development. The association of histone Kla with various metabolic processes, particularly glycolysis and glutamine metabolism, underscores its pivotal role in metabolic reprogramming, including in cancerous tissues, where it contributes to tumorigenesis, immune evasion, and angiogenesis. In addition, histone Kla is involved in the pathogenesis of various diseases, particularly several cancers and neurodegenerative diseases. The identification of histone Kla opens new avenues for therapeutic interventions targeting specific Kla sites. In this review, we summarize the differences between histone Kla modifications and other acylation modifications, discuss the mechanisms and roles of histone Kla in disease, and conclude by describing existing drugs and potential targets. This study provides new insights into the mechanisms linking histone Kla to diseases and into the discovery of new drugs and targets.
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Histonas , Animales , Humanos , Epigénesis Genética/fisiología , Histonas/metabolismo , Lisina/metabolismo , Lisina/química , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Procesamiento Proteico-Postraduccional/fisiología , Código de HistonasRESUMEN
Glutathione (GSH), a robust endogenous antioxidant, actively participates in the modulation of the redox status of cysteine residues in proteins. Previous studies have indicated that GSH can prevent ß-cell failure and prediabetes caused by chronic oscillating glucose (OsG) administration. However, the precise mechanism underlying the protective effect is not well understood. Our current research reveals that GSH is capable of reversing the reduction in Nrf2 levels, as well as downstream genes Grx1 and HO-1, in the islet ß-cells of rats induced by chronic OsG. In vitro experiments have further demonstrated that GSH can prevent ß-cell dedifferentiation, apoptosis, and impaired insulin secretion caused by OsG. Additionally, GSH facilitates the translocation of Nrf2 into the nucleus, resulting in an upregulation of Nrf2-targeted genes such as GCLC, Grx1, HO-1, and NQO1. Notably, when the Nrf2 inhibitor ML385 is employed, the effects of GSH on OsG-treated ß-cells are abrogated. Moreover, GSH enhances the S-glutathionylation of Keap1 at Cys273 and Cys288, but not Cys151, in OsG-treated ß-cells, leading to the dissociation of Nrf2 from Keap1 and facilitating Nrf2 nuclear translocation. In conclusion, the protective role of GSH against OsG-induced ß-cell failure can be partially attributed to its capacity to enhance Keap1 S-glutathionylation, thereby activating the Nrf2 signaling pathway. These findings provide novel insights into the prevention and treatment of ß-cell failure in the context of prediabetes/diabetes, highlighting the potential of GSH.
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BACKGROUND: Ovarian granulosa cell tumors (OGCTs) feature low incidence, indolent growth and late recurrence. Treatment for recurrent OGCTs is challenging. METHODS: The present study was designed to explore the prognostic factors and establish a nomogram to predict cancer-specific survival (CSS) for OGCTs patients. Enrolled in the study were 1459 eligible patients in the Surveillance, Epidemiology, and End Results (SEER) database, who were randomized to the training (n = 1021) or testing set (n = 438) at a ratio of 7:3. Univariate and multivariate Cox regression analyses were employed to screen the prognostic factors. The predictors were determined by using the Least absolute shrinkage and selection operator (LASSO) regression analysis. The model was constructed via the Cox proportional hazards risk regression analysis. The performance and clinical value of the nomograms was assessed with C-index, calibration plots, and decision curve analysis. RESULTS: Age, pTNM stage, tumor size, surgery of the primary tumor, surgery of regional lymph nodes (LNs), residual disease after surgery, and chemotherapy were considered as significant predictive factors for CSS in OGCTs patients. After screening, the prognostic factors except surgery of regional LNs and chemotherapy were employed to build the nomogram. With desirable discrimination and calibration, the nomogram was more powerful in predicting CSS than the American Joint Committee on Cancer staging system in clinical use. CONCLUSION: This novel prognostic nomogram, which comprises a stationary nomogram and a web-based calculator, offers convenience for clinicians in personalized decision-making including optimal treatment plans and prognosis assessments for OGCTs patients.
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Tumor de Células de la Granulosa , Nomogramas , Humanos , Femenino , Pronóstico , Tumor de Células de la Granulosa/diagnóstico , Tumor de Células de la Granulosa/terapia , Bases de Datos FactualesRESUMEN
Radiative cooling (RC) is a carbon-neutral cooling technology that utilizes thermal radiation to dissipate heat from the Earth's surface to the cold outer space. Research in the field of RC has garnered increasing interest from both academia and industry due to its potential to drive sustainable economic and environmental benefits to human society by reducing energy consumption and greenhouse gas emissions from conventional cooling systems. Materials innovation is the key to fully exploit the potential of RC. This review aims to elucidate the materials development with a focus on the design strategy including their intrinsic properties, structural formations, and performance improvement. The main types of RC materials, i.e., static-homogeneous, static-composite, dynamic, and multifunctional materials, are systematically overviewed. Future trends, possible challenges, and potential solutions are presented with perspectives in the concluding part, aiming to provide a roadmap for the future development of advanced RC materials.
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Flexible thermoelectric devices show great promise as sustainable power units for the exponentially increasing self-powered wearable electronics and ultra-widely distributed wireless sensor networks. While exciting proof-of-concept demonstrations have been reported, their large-scale implementation is impeded by unsatisfactory device performance and costly device fabrication techniques. Here, we develop Ag2Se-based thermoelectric films and flexible devices via inkjet printing. Large-area patterned arrays with microscale resolution are obtained in a dimensionally controlled manner by manipulating ink formulations and tuning printing parameters. Printed Ag2Se-based films exhibit (00 l)-textured feature, and an exceptional power factor (1097 µWm-1K-2 at 377 K) is obtained by engineering the film composition and microstructure. Benefiting from high-resolution device integration, fully inkjet-printed Ag2Se-based flexible devices achieve a record-high normalized power (2 µWK-2cm-2) and superior flexibility. Diverse application scenarios are offered by inkjet-printed devices, such as continuous power generation by harvesting thermal energy from the environment or human bodies. Our strategy demonstrates the potential to revolutionize the design and manufacture of multi-scale and complex flexible thermoelectric devices while reducing costs, enabling them to be integrated into emerging electronic systems as sustainable power sources.
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Background: Alternative splicing (AS) is a biological process that allows genes to be translated into diverse proteins. However, aberrant AS can predispose cells to aberrations in biological mechanisms. RNA binding proteins (RBPs), closely affiliated with AS, have gained increased attention in recent years. Among these RBPs, RBM25 has been reported to participate in the cardiac pathological mechanism through regulating AS; however, the involvement of RBM25 as a splicing factor in heart failure remains unclarified. Methods: RBM25 was overexpressed in H9c2 cells to explore the target genes bound and regulated by RBM25 during heart failure. RNA sequencing (RNA-seq) was used to scrutinize the comprehensive transcriptional level before identifying AS events influenced by RBM25. Further, improved RNA immunoprecipitation sequencing (iRIP-seq) was employed to pinpoint RBM25-binding sites, and RT-qPCR was used to validate specific genes modulated by RBM25. Results: RBM25 was found to upregulate the expression of genes pertinent to the inflammatory response and viral processes, as well as to mediate the AS of genes associated with cellular apoptosis and inflammation. Overlap analysis between RNA-seq and iRIP-seq suggested that RBM25 bound to and manipulated the AS of genes associated with inflammation in H9c2 cells. Moreover, qRT-PCR confirmed Slc38a9, Csf1, and Coro6 as the binding and AS regulatory targets of RBM25. Conclusion: Our research implies that RBM25 plays a contributory role in cardiac inflammatory responses via its ability to bind to and regulate the AS of related genes. This study offers preliminary evidence of the influence of RBM25 on inflammation in H9c2 cells.
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Empalme Alternativo , Insuficiencia Cardíaca , Proteínas con Motivos de Reconocimiento de ARN , Factores de Empalme de ARN , Empalme Alternativo/genética , Insuficiencia Cardíaca/genética , Inflamación/genética , Proteínas Nucleares/genética , Proteínas de Unión al ARN/genética , Animales , Ratas , Factores de Empalme de ARN/genética , Proteínas con Motivos de Reconocimiento de ARN/genéticaRESUMEN
Plastic products have become ubiquitous in society, and entered various ecosystems due to the massive scale of production. The United Nations Environment Program (UNEP) has listed microplastics (MPs), which form when plastic remnants degrade, as a global emerging pollutant, and the association between soil pollution and MPs has become a popular research topic. This paper systematically reviews research focusing on MP-related soil pollution from the past 10 years (2012-2022), with the identified papers demonstrating that interactions between MPs and soil aggregates has become a research frontier in the field. The presented research provides evidence that soil aggregates are important storage sites for MPs, and that storage patterns of MPs within soil aggregates are influenced by MP characteristics. In addition, MPs affect the formation, turnover, and stability of soil aggregates through the introduction of fracture points along with diverse physicochemical characteristics such as composition and specific surface area. The current knowledge base includes certain issues and challenges that could be addressed in future research by extending the spatial and temporal scales over which microplastic-soil aggregate interactions are studied, unifying quantitative and qualitative methods, and tracing the fates of MPs in the soil matrix. This review contributes to enriching our understanding of how terrestrial MPs interact with soil aggregates, and whether they pose a risk to soil health.
RESUMEN
The sustainability of water resources is a major challenge for the Ordos Basin and Loess Plateau of China. The basis of effective water management is an understanding of the water cycle process. This study investigated the surface water-groundwater origins and connectivity using stable isotopes (δD and δ18O) of surface water and groundwater in 11 river basins in the Ordos Basin. It was found that the surface water-groundwater origins and hydraulic connection were characterized by regional differences, mainly induced by climatic characteristics, hydrogeological conditions and human activities. Specifically, the impact of thick loess deposits caused surface water and groundwater to take long time to produce a hydraulic connection. In contrast, areas with thin loess deposits and frequent human activities showed a good connectivity between surface water and groundwater. As for water origins, summer precipitation was a common source of surface water and groundwater in the study area, and groundwater discharge was another source of surface water. However, surface water and groundwater were subjected to different degrees of evaporation during receiving precipitation recharge. Notably, thick loess deposits had an impact on groundwater evaporation because both the recharge of precipitation to groundwater and the discharge of groundwater to surface water took a long time. In addition, it was found that frequent human activities (mining, irrigation and urban construction) could weaken the impact of evaporation. This large-scale analysis provided new insights into the origins and connectivity of surface water and groundwater in areas with thick unsaturated zones for water resources management.
Asunto(s)
Agua Subterránea , Hidrógeno , Humanos , Isótopos de Oxígeno/análisis , Agua , Monitoreo del Ambiente , Isótopos/análisis , Ríos , ChinaRESUMEN
Hypoxia, the hallmark of malignant tumors, has been recognized as a major obstacle for photodynamic therapy (PDT). Precisely targeting cancer cells in intricate biological scenarios by a hypoxia-resistant photosensitizer (PS) is the cornerstone to conquer the inevitable tumor recurrence and metastasis. Herein, we describe an organic NIR-II PS (TPEQM-DMA) possessing potent type-I phototherapeutic efficacy to overcome the intrinsic pitfalls of PDT in combating hypoxic tumors. TPEQM-DMA exhibited prominent NIR-II emission (>1000 nm) with an aggregation-induced emission feature and efficiently produced superoxide anion and hydroxyl radical in the aggregate state under white light irradiation exclusively through a low-O2-dependent type-I photochemical process. The suitable cationic nature assisted TPEQM-DMA to accumulate in cancerous mitochondria. Meanwhile, the PDT of TPEQM-DMA impaired the cellular redox homeostasis, led to the mitochondrial dysfunction, and raised the level of lethal peroxidized lipids, which induced cellular apoptosis and ferroptosis. This synergistic cell death modality enabled TPEQM-DMA to suppress the growth of cancer cells, multicellular tumor spheroids, and tumors. To improve the pharmacological properties of TPEQM-DMA, TPEQM-DMA nanoparticles were prepared by encapsulation of polymer. In vivo experiments proved the appealing NIR-II fluorescence imaging-guided PDT effect of TPEQM-DMA nanoparticles for tumors.
Asunto(s)
Ferroptosis , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Neoplasias/tratamiento farmacológico , Nanopartículas/química , Apoptosis , Mitocondrias , Hipoxia , Línea Celular TumoralRESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.