RESUMEN
Developing a synthesis-free, multifunctional, and effective colorimetric assay system based on 3,3',5,5'-tetramethylbenzidine (TMB) oxidation is attractive yet challenging. Herein, we established a synergetic Cu2+/Cr6+-promoting strategy for TMB-based colorimetric detection of Cr6+. By introducing Cu2+, critical TMB·+···Cu(I/II)···TMB charge transfer complex (TMC) intermediates were in situ formed to reduce the activation energy of TMB oxidation, thereby accelerating Cr6+-mediated TMB oxidation. TMC intermediates also played a pivotal role in H2O2-participated TMB oxidation, clarifying the secondary responsibility of reactive oxygen species frequently caused by Fenton-like reactions. Leveraging the synergetic capacity between Cu2+ and Cr6+ for TMB oxidation, we demonstrated sensitive and specific colorimetric detections for Cr6+ with a limit of detection of 0.006 µM. With its convenient operation and rapid responsiveness, this strategy successfully enabled the practical detection of Cr6+ in real water samples. This work not only enhances the understanding of the internal acceleration mechanism in colorimetric sensing but also provides valuable opportunities to advance synthesis-free detection platforms.
RESUMEN
BACKGROUND: Elevated extracellular matrix (ECM) accumulation is a major contributing factor to the pathogenesis of fibrotic diseases. Recent studies have indicated that N6-methyladenosine (m6A) RNA modification plays a pivotal role in modulating RNA stability and contribute to the initiation of various pathological conditions. Howbeit, the precise mechanism by which m6A influences ECM deposition remains unclear. METHODS: In this study, we used hypertrophic scars (HTSs) as a paradigm to investigate ECM-related diseases. We focused on the role of ALKBH5-mediated m6A demethylation within the pathological progression of HTSs and examined its correlation with clinical stages. The effects of ALKBH5 ablation on ECM components were studied both in vivo and in vitro. Downstream targets of ALKBH5, along with their underlying mechanisms, were identified using integrated high-throughput analysis, RNA-binding protein immunoprecipitation and RNA pull-down assays. Furthermore, the therapeutic potential of exogenous ALKBH5 overexpression was evaluated in fibrotic scar models. RESULTS: ALKBH5 was decreased in fibroblasts derived from HTS lesions and was negatively correlated with their clinical stages. Importantly, ablation of ALKBH5 promoted the expression of COL3A1, COL1A1, and ELN, leading to pathological deposition and reconstruction of the ECM both in vivo and in vitro. From a therapeutic perspective, the exogenous overexpression of ALKBH5 significantly inhibited abnormal collagen deposition in fibrotic scar models. As determined by integrated high-throughput analysis, key ECM components including COL3A1, COL1A1, and ELN are direct downstream targets of ALKBH5. By means of its mechanism, ALKBH5 inhibits the expression of COL3A1, COL1A1, and ELN by removing m6A from mRNAs, thereby decreasing their stability in a YTHDF1-dependent manner. CONCLUSIONS: Our study identified ALKBH5 as an endogenous suppressor of pathological ECM deposition, contributing to the development of a reprogrammed m6A-targeted therapy for HTSs.
Asunto(s)
Desmetilasa de ARN, Homólogo 5 de AlkB , Matriz Extracelular , Fibrosis , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Matriz Extracelular/metabolismo , Fibrosis/metabolismo , Humanos , Ratones , Animales , Desmetilación , Colágeno Tipo III/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Masculino , Cadena alfa 1 del Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I/metabolismo , Fibroblastos/metabolismoRESUMEN
The application of low-condensation diesel in cold regions with extremely low ambient temperatures (-14 to -29 °C) has enabled the operation of diesel vehicles. Still, it may contribute to heavy haze pollution in cold regions during winter. Here we examine pollutant emissions from low-condensation diesel in China. We measure the emissions of elemental carbon (EC), organic carbon (OC), and elements, including heavy metals such as arsenic (As). Our results show that low-condensation diesel increased EC and OC emissions by 2.5 and 2.6 times compared to normal diesel fuel, respectively. Indicators of vehicular sources, including EC, As, lead (Pb), cadmium (Cd), chromium (Cr), nickel (Ni), and manganese (Mn), increased by approximately 20.2-162.5% when using low-condensation diesel. Seasonal variation of vehicular source indicators, observed at road site ambient environments revealed the enhancement of PM2.5 pollution by the application of low-condensation diesel in winter. These findings suggest that -35# diesel, a low-cetane index diesel, may enhance air pollution in winter, according to a dynamometer test conducted in laboratory. It raises questions about whether higher emissions are released if -35# diesel is applied to running vehicles in real-world cold ambient environments.
RESUMEN
BACKGROUND: After receiving neoadjuvant chemoradiation, the number of examined lymph nodes in resectable gastroesophageal cancer (GEC) will decrease, this may not accurately determine the N staging. So our study evaluates the clinical significance of a new staging model based on the logarithmic odds of positive lymph nodes (LODDS) in patients with GEC after receiving neoadjuvant chemoradiation. METHODS: A total of 1 130 patients with pathologically diagnosed GEC who received neoadjuvant chemoradiation from 2004 to 2019 included in the National Cancer Institute Surveillance, Epidemiology, and Results (SEER) database were selected for analysis. Lymph nodes were staged according to the AJCC TNM staging system (eighth edition) and LODDS. Patient prognosis across the two systems were evaluated by the Kaplan-Meier method, differences in node staging were evaluated by the Akaike information criterion and Bayesian information criterion. In addition, 914 patients from our center were externally validated. RESULTS: Compared to the traditional TNM staging system, the new TLODDSM staging system was comprised of stage I, stage II, stage IIIA, stage IIIB, and stage IVA, and decision curve analysis showed that the new staging system had higher benefits for different decision thresholds than the old staging system. The Akaike information criterion and Bayesian information criterion of the new staging system was lower than those of the old staging system, indicating the sensitivity of the TLODDSM staging system for predicting the prognosis of patients was higher. In addition, stage-IIIB or -IVA patients in the new staging system benefited from adjuvant chemotherapy. The externally validated data from our center supported this conclusion. CONCLUSIONS: Compared to the TNM staging system, the TLODDSM staging system has significant advantages in predicting prognosis of patients with GEC who have completed neoadjuvant chemoradiation, guiding the adjuvant chemotherapy for patients.
Asunto(s)
Neoplasias Esofágicas , Ganglios Linfáticos , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Gástricas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Anciano , Ganglios Linfáticos/patología , Quimioradioterapia , Adulto , Estimación de Kaplan-Meier , Oportunidad Relativa , Programa de VERF , Reproducibilidad de los Resultados , Metástasis LinfáticaRESUMEN
INTRODUCTION: Benign esophageal tumors are uncommon, accounting for approximately 2% of esophageal tumors. Esophageal schwannoma is a much rarer solid tumor with few cases reported in the literature. Open surgery is the surgical approach of choice for the treatment of esophageal tumors. With the advent of thoracoscopy, more and more countries are adopting a thoracoscopic approach to treat esophageal tumors, but there is still no clear surgical standard or modality for the treatment of esophageal tumors. PATIENT CONCERNS: A 50-year-old woman was admitted to our hospital. Over the past 2 months, her clinical presentation has included progressively worse swallowing disorder and weight loss. Gastroscopy showed an elevated lesion with a smooth surface visible 18 cm out from the incisors. An electron circumferential ultrasound endoscopy showed a hemispherical bulge with a smooth surface 18 to 23 cm from the incisor; the bulge originated from the intrinsic muscular layer and showed a heterogeneous mixed moderate ultrasound with a little blood flow signal and blue-green elastography in 1 of the sections measuring approximately 4 cmâ ×â 3 cm. Chest computed tomography (CT) showed a mass-like soft tissue shadow in the upper esophagus measuring approximately 39 mmâ ×â 34 mm, with a CT The lumen was compressed and narrowed, and the lumen of the upper part of the lesion was dilated, and the adjacent trachea was compressed and displaced to the right. INTERVENTIONS: After completion of the examination, assisted by artificial pneumothorax and thoracoscopic resection of esophageal masses were performed. DIAGNOSIS AND OUTCOMES: Postoperative pathology report: Mesenchymal-derived tumor (esophagus), combined with immunohistochemical staining results and morphologic features supported schwannoma. The patient's postoperative course was calm. The patient's postoperative dysphagia subsided. CONCLUSION: We describe a case of successful treatment of a schwannoma of the upper esophagus using artificial pneumothorax-assisted VATS. The combined use of Sox10 and S100 helps to improve the sensitivity and specificity of schwannoma diagnosis. Damage to the esophageal lining was avoided by mixed thoracoscopic and endoscopic exploration. This approach can also be applied to benign esophageal tumors in the thoracic and subthoracic segments, leading to better minimally invasive results.
Asunto(s)
Neoplasias Esofágicas , Neurilemoma , Toracoscopía , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/diagnóstico , Femenino , Persona de Mediana Edad , Neurilemoma/cirugía , Neurilemoma/patología , Neurilemoma/diagnóstico , Neurilemoma/diagnóstico por imagen , Toracoscopía/métodosRESUMEN
The high-intactness and ultraclean fabrication of suspended 2D materials has always been a challenge due to their atomically thin nature. Here, we present a universal polymer-free transfer approach for fabricating suspended 2D materials by using volatile micro-molecule cyclododecane as the transfer medium, thus ensuring the ultraclean and intact surface of suspended 2D materials. For the fabricated monolayer suspended graphene, the intactness reaches 99% for size below 10 µm and suspended size reaches 36 µm. Owing to the advantages of ultra-cleanness and large size, the thermal conductivity reaches 4914 W m - 1 K - 1 at 338 K. Moreover, this strategy can also realize efficient batch transfer of suspended graphene and is applicable for fabricating other 2D suspended materials such as MoS2. Our research not only establishes foundation for potential applications and investigations of intrinsic properties of large-area suspended 2D materials, but also accelerates the wide applications of suspended graphene grid in ultrahigh-resolution TEM characterization.
RESUMEN
This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11.
RESUMEN
Nucleases play pivotal roles in DNA repair and apoptosis. Moreover, they have various applications in biotechnology and industry. Among nucleases, TatD has been characterized as an exonuclease with various biological functions in different organisms. Here, we biochemically characterized the potential TatD nuclease from Thermus thermophilus. The tatD gene from T. thermophilus was cloned, then the recombinant TatD nuclease was expressed and purified. Our results revealed that the TthTatD nuclease could degrade both single-stranded and double-stranded DNA, and its activity is dependent on the divalent metal ions Mg2+ and Mn2+. Remarkably, the activity of TthTatD nuclease is highest at 37 °C and decreases with increasing temperature. TthTatD is not a thermostable enzyme, even though it is from a thermophilic bacterium. Based on the sequence similarity and molecular docking of the DNA substrate into the modeled TthTatD structure, several key conserved residues were identified and their roles were confirmed by analyzing the enzymatic activities of the site-directed mutants. The residues E86 and H149 play key roles in binding metal ions, residues R124/K126 and K211/R212 had a critical role in binding DNA substrate. Our results confirm the enzymatic properties of TthTatD and provide a primary basis for its possible application in biotechnology.
Asunto(s)
Proteínas Bacterianas , Thermus thermophilus , Thermus thermophilus/enzimología , Thermus thermophilus/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/aislamiento & purificación , Simulación del Acoplamiento Molecular , Clonación Molecular , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/química , Exodesoxirribonucleasas/metabolismoRESUMEN
The present study aimed to assess the relationship between body shape, physical activity (PA), and systolic blood pressure (SBP) and diastolic blood pressure (DBP). A novel visualization method was used to examine the effects of body shape combined with physical activity on hypertension. Data from 54,303 participants were obtained from the China Health and Nutrition Survey (CHNS) and analyzed using logistic regression models and standardized regression coefficients of linear models. These models were used to explore factors and effects of body shape indices and other parameters on SBP and DBP. The logistic regression model revealed that compared to transport-related PA, the aggregated variables (weight and waist) were associated with a 2.44-fold and 1.65-fold increase in the risk of hypertension, respectively (p < .05). The average aggregated standardized coefficient of the linear model, based on 1000 bootstrap resamples, indicated that the Base Shape group had the strongest explanatory power for hypertension, followed by the Habits group. However, the explanatory power of the PA group was around 10 and 22 times lower than that of the Base Shape group for DBP and SBP, respectively (p < .05). These results demonstrate that increasing physical activity, with emphasizing a healthy body shape, and adopting positive lifestyle habits can effectively contribute to the prevention and control of hypertension.
Asunto(s)
Ejercicio Físico , Hipertensión , Humanos , Masculino , Persona de Mediana Edad , Femenino , China , Adulto , Población Urbana , Anciano , Presión Sanguínea/fisiología , Encuestas Nutricionales , Factores de RiesgoRESUMEN
Aflatoxin B1 (AFB1) contamination is a food safety issue threatening human health globally. Biodegradation is an effective method for overcoming this problem, and many microorganisms have been identified as AFB1-degrading strains. However, the response mechanisms of these microbes to AFB1 remain unclear. More degrading enzymes, especially of new types, need to be discovered. In this study, a novel AFB1-degrading strain, DDC-4, was isolated using coumarin as the sole carbon source. This strain was identified as Bacillus halotolerans through physiological, biochemical, and molecular methods. The strain's degradation activity was predominantly attributable to thermostable extracellular proteins (degradation rate remained approximately 80% at 90 °C) and was augmented by Cu2+ (95.45% AFB1 was degraded at 48 h). Alpha/beta hydrolase (arylesterase) was selected as candidate AFB1-degrading enzymes for the first time as a gene encoding this enzyme was highly expressed in the presence of AFB1. Moreover, AFB1 inhibited many genes involved in the nucleotide synthesis of strain DDC-4, which is possibly the partial molecular mechanism of AFB1's toxicity to microorganisms. To survive under this stress, sporulation-related genes were induced in the strain. Altogether, our study identified a novel AFB1-degrading strain and explained its response mechanisms to AFB1, thereby providing new insights for AFB1 biodegradation.
Asunto(s)
Aflatoxina B1 , Bacillus , Aflatoxina B1/metabolismo , Bacillus/metabolismo , Bacillus/genética , Biodegradación Ambiental , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
The disparity between growth substrates and application-specific substrates can be mediated by reliable graphene transfer, the lack of which currently strongly hinders the graphene applications. Conventionally, the removal of soft polymers, that support the graphene during the transfer, would contaminate graphene surface, produce cracks, and leave unprotected graphene surface sensitive to airborne contaminations. In this work, it is found that polyacrylonitrile (PAN) can function as polymer medium for transferring wafer-size graphene, and encapsulating layer to deliver high-performance graphene devices. Therefore, PAN, that is compatible with device fabrication, does not need to be removed for subsequent applications. The crack-free transfer of 4 in. graphene onto SiO2/Si wafers, and the wafer-scale fabrication of graphene-based field-effect transistor arrays with no observed clear doping, uniformly high carrier mobility (≈11 000 cm2 V-1 s-1), and long-term stability at room temperature, are achieved. This work presents new concept for designing the transfer process of 2D materials, in which multifunctional polymer can be retained, and offers a reliable method for fabricating wafer-scale devices of 2D materials with outstanding performance.
RESUMEN
Bacterial RecJ exhibits 5'â3' exonuclease activity that is specific to ssDNA; however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.
Asunto(s)
Proteínas Arqueales , Proteínas Arqueales/química , Proteínas Arqueales/metabolismo , Proteínas Arqueales/genética , Cristalografía por Rayos X , Methanocaldococcus/enzimología , Methanocaldococcus/metabolismo , Unión Proteica , Multimerización de Proteína , ADN Helicasas/metabolismo , ADN Helicasas/química , ADN Helicasas/genética , Modelos Moleculares , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/química , Exodesoxirribonucleasas/genéticaRESUMEN
Recent years have witnessed advances in chemical vapor deposition growth of graphene films on metal foils with fine scalability and thickness controllability. However, challenges for obtaining wrinkle-free, defect-free and large-area uniformity remain to be tackled. In addition, the real commercial applications of graphene films still require industrially compatible transfer techniques with reliable performance of transferred graphene, excellent production capacity, and suitable cost. Transferred graphene films, particularly with a large area, still suffer from the presence of transfer-related cracks, wrinkles and contaminants, which would strongly deteriorate the quality and uniformity of transferred graphene films. Potential applications of graphene films include moisture barrier films, transparent conductive films, electromagnetic shielding films, and optical communications; such applications call different requirements for the performance of transferred graphene, which, in turn, determine the suitable transfer techniques. Besides the reliable transfer process, automatic machines should be well developed for the future batch transfer of graphene films, ensuring the repeatability and scalability. This mini-review provides a summary of recent advances in the transfer of graphene films and offers a perspective for future directions of transfer techniques that are compatible for industrial batch transfer.
RESUMEN
BACKGROUND: Enhancing angiogenesis may be an effective strategy to promote functional recovery after ischemic stroke. Inflammation regulates angiogenesis. Microglia are crucial cells that initiate inflammatory responses after various brain injuries. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a role in regulating brain injury. This study aimed to explore the effects of NEAT1-regulated microglial polarization on the neovascularization capacity of cerebrovascular endothelial cells and the underlying molecular regulatory mechanisms. METHODS: Mouse cerebral arterial endothelial cells (mCAECs) were co-cultured with BV-2 cells in different groups using a Transwell system. NEAT1 expression levels were measured by fluorescence quantitative reverse transcription PCR. Levels of IL-1ß, IL-6, TNF-α, Arg-1, IL-4, and IL-10 were determined using ELISA. Expression levels of CD86 and CD163 were detected by immunofluorescence. The neovascularization capacity of mCAECs was assessed using CCK-8, Transwell, Transwell-matrigel, and tube formation assays. Label-free quantification proteomics was carried out to identify differentially expressed proteins. Protein levels were measured by Western blotting. RESULTS: NEAT1 overexpression induced M1 polarization in BV-2 cells, whereas NEAT1 knockdown blocked lipopolysaccharide-induced M1 polarization in microglia. NEAT1-overexpressing BV-2 cells suppressed the angiogenic ability of mCAECs, and NEAT1-knocking BV-2 cells promoted the angiogenic ability of mCAECs under lipopolysaccharide treatment. Label-free quantitative proteomic analysis identified 144 upregulated and 131 downregulated proteins that were induced by NEAT1 overexpression. The AMP-activated protein kinase (AMPK) signaling pathway was enriched in the Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed proteins. Further verification showed that NEAT1 inactivated the AMPK signaling pathway. Moreover, the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide reversed the effect of NEAT1 on BV-2 polarization and the regulatory effect of NEAT1-overexpressing BV-2 cells on the angiogenic ability of mCAECs. CONCLUSIONS: NEAT1 inhibits the angiogenic activity of mCAECs by inducing M1 polarization of BV-2 cells through the AMPK signaling pathway. This study further clarified the impact and mechanism of NEAT1 on microglia and the angiogenic ability of cerebrovascular endothelial cells.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Células Endoteliales , Microglía , ARN Largo no Codificante , Transducción de Señal , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , Ratones , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Arterias Cerebrales/metabolismo , Arterias Cerebrales/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/genética , Línea Celular , Polaridad Celular/efectos de los fármacosRESUMEN
Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.
Asunto(s)
Proteínas Potenciadoras de Unión a CCAAT , Matriz Extracelular , Queloide , ARN Largo no Codificante , Queloide/genética , Queloide/metabolismo , Queloide/patología , Humanos , ARN Largo no Codificante/genética , Matriz Extracelular/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Animales , Ratones , Regulación de la Expresión Génica , Fibroblastos/metabolismo , Regiones Promotoras Genéticas , Masculino , Regulación hacia ArribaRESUMEN
The purpose of this study was to design a novel antioxidant and antibacterial film for food packaging using food-grade raw materials. The films were designed and fabricated based on carboxymethyl chitosan and pectin incorporated with procyanidins (PCs) and phycocyanin (Phy) by the tape casting method. The effects of different proportions of PCs and Phy on the properties and functions of the prepared films were studied. The results showed that the thickness of films could range from 55 to 70 µm, with dense network structure and uniform distribution of elements. Compared with C-Film group, the film loaded with PCs and Phy had lower water solubility and swelling rate, and higher tensile strength and elongation at break. FITR and XRD spectra revealed the molecular interaction mechanism among carboxymethyl chitosan, pectin, PCs and Phy, which could effectively endow the films with ultraviolet barrier properties. Moreover, the addition of PCs and Phy could effectively improve the antioxidant capacity and antibacterial effect of films, for example, the free radical scavenging abilities of most films were above 80% when the concentration of PCs was 40 µg mL-1. In view of these functional properties, the prepared film containing PCs and Phy have been successfully used in food packaging, which was proved by the preservation experiment of grapes. This study can provide theoretical and technical guidance for the preparation of biodegradable antibacterial films, and their application in the food packaging field.
RESUMEN
PURPOSE: This study aimed to evaluate the protective effects of gentiopicroside against lipopolysaccharide-induced chondrocyte inflammation. METHODS: SW 1353 chondrosarcoma cells were stimulated with LPS (5 µg/ml) for 24 h and treated with different concentrations of gentiopicroside (GPS) for 24 h. The toxic effects of GPS on chondrocytes were determined using a CCK-8 assay and EdU staining. Western blotting, qPCR, and immunofluorescence analysis were used to examine the protective effect of GPS against the inflammatory response in chondrocytes induced by lipopolysaccharide (LPS). One-way ANOVA was used to compare the differences between the groups (significance level of 0.05). RESULTS: The CCK-8 results showed that 10, 20 and 40 µM GPS had no significant toxic effects on chondrocytes; GPS effectively reduced the production of IL-1ß and PGE2, reversed LPS-induced extracellular matrix degradation in cartilage by inhibiting the Stat3/Runx2 signaling pathway, and suppressed the hypertrophic transformation of SW 1353 chondrosarcoma cells. CONCLUSION: Our study demonstrated that GPS significantly inhibited the LPS-induced inflammatory response and hypertrophic cellular degeneration in SW 1353 chondrosarcoma cells and is a valuable traditional Chinese medicine for the treatment of knee osteoarthritis.
Asunto(s)
Condrosarcoma , Glucósidos Iridoides , Osteoartritis , Humanos , Condrocitos/metabolismo , Lipopolisacáridos/toxicidad , Osteoartritis/metabolismo , Sincalida/metabolismo , Sincalida/farmacología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Hipertrofia , Condrosarcoma/tratamiento farmacológico , Interleucina-1beta/metabolismo , FN-kappa B/metabolismoRESUMEN
Background: Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) poses a serious health threat and becomes a new challenge. T2DM patients with CKD fall into three categories, diabetic nephropathy (DN), non-diabetic kidney disease (NDKD), and diabetic nephropathy plus non-diabetic kidney disease (DN + NDKD), according to kidney biopsy. The purpose of our study was to compare the clinical characteristics and kidney outcomes of DN, NDKD, and DN + NDKD patients. Methods: Data on clinical characteristics, pathological findings, and prognosis were collected from June 2016 to July 2022 in patients with previously diagnosed T2DM and confirmed DN and or NDKD by kidney biopsy at Tongji Hospital in Wuhan, China. The endpoint was defined as kidney transplantation, dialysis, or a twofold increase in serum creatinine. Results: In our 6-year retrospective cohort research, a total of 268 diabetic patients were admitted and categorized into three groups by kidney biopsy. The 268 patients were assigned to DN (n = 74), NDKD (n = 109), and DN + NDKD (n = 85) groups. The most frequent NDKD was membranous nephropathy (MN) (n = 45,41.28%). Hypertensive nephropathy was the most common subtype in the DN+NDKD group (n = 34,40%). A total of 34 patients (12.7%) reached the endpoint. The difference between the Kaplan-Meier survival curves of the DN, NDKD, and DN + NDKD groups was significant (p < 0.05). Multifactorial analysis showed that increased SBP [HR (95% CI): 1.018(1.002-1.035), p = 0.025], lower Hb [HR(95% CI): 0.979(0.961-0.997), p = 0.023], higher glycosylated hemoglobin [HR(95% CI): 1.338(1.080-1.658), p = 0.008] and reduced serum ALB [HR(95% CI): 0.952(0.910-0.996), p = 0.032] were risk factors for outcomes in the T2DM patients with CKD. Conclusions: This research based on a Chinese cohort demonstrated that the risk of endpoint events differed among DN, NDKD, and DN+NDKD patients. In T2DM patients with CKD, DN patients displayed worse kidney prognosis than those with NDKD or DN + NDKD. Increased SBP, higher glycosylated hemoglobin, lower Hb, and decreased serum ALB may be correlated with adverse kidney outcomes in T2DM patients.
Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Nefropatías Diabéticas/terapia , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina Glucada , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/complicacionesRESUMEN
Introduction: Pineal cysts have long been considered a benign intracranial variation. However, in our clinical practice, it has been observed that some children with central precocious puberty (CPP) who have pineal cysts experience rapid progression in adolescent development. In recent years, there has been a significant increase in the prevalence of CPP in girls, leading to more diagnoses of CPP among children with pineal cysts. Despite this, there is no consensus regarding whether pineal cysts contribute to CPP as one of its organic factors. This study aimed to analyze the clinical characteristics of pineal cysts in children with CPP and explore the potential effects of pineal cysts on puberty development. Methods: This single-center study retrospectively analyzed clinical data from girls aged 3 to 10 years who underwent head/pituitary magnetic resonance imaging at the Children's Hospital Affiliated to Zhengzhou University between 2019 and 2022. The study categorized the detection rates of pineal cysts based on systematic disease classification and compared the rates of cyst detection between girls diagnosed with CPP and those without CPP. Subsequently, CPP-diagnosed girls with pineal cysts were examined. Among CPP-diagnosed girls meeting the study's criteria, those with pineal cysts formed the 'cyst group,' while those without cysts were matched in a 1:1 ratio based on age and body mass index to form the 'non-cyst group.' Comparative analyses were conducted to assess the clinical characteristics between these two groups. CPP-diagnosed girls with cysts were further subdivided into three groups according to cyst size (≤5 mm, 5.1-9.9 mm, and ≥10 mm) to investigate potential differences in clinical characteristics among these subgroups. The study involved an analysis of clinical data from girls diagnosed with CPP and included imaging follow-ups to explore the progression of pineal cysts over time. Results: Among the 23,245 girls who underwent head/pituitary magnetic resonance imaging scans, the detection rate of pineal cysts was 3.6% (837/23,245), with most cases being associated with endocrine diseases. The detection rate of pineal cysts in CPP patients was 6.4% (262/4099), which was significantly higher than the 3.0% (575/19,146) in patients without CPP. In comparison to the non-cyst group, the cyst group exhibited statistically significant increases in estradiol levels, peak luteinizing hormone (LH) levels, peak LH/follicle-stimulating hormone (FSH) ratios, uterine body length, and cervix length (P < 0.001). As cyst size increased, there were significant rises in LH peak, peak LH/FSH ratio, uterine body length, and cervical length (P < 0.01). Estradiol levels and left ovarian volume also showed an increasing trend (P < 0.05). Among girls who underwent follow-up imaging, 26.3% (5/19) exhibited an increase in cyst size. Conclusion: Pineal cysts are relatively common in children with CPP. They may affect the pubertal development process, with larger cysts correlating to faster pubertal development. Therefore, the authors hypothesize that pineal cysts may trigger CPP in some cases, especially when the cysts are larger than 5 mm in size, as indicated by our data.
Asunto(s)
Quistes del Sistema Nervioso Central , Quistes , Pubertad Precoz , Niño , Femenino , Humanos , Adolescente , Hormona Luteinizante , Pubertad Precoz/diagnóstico , Estudios Retrospectivos , Hormona Folículo Estimulante , Quistes/complicaciones , Quistes/diagnóstico por imagen , Hormona Folículo Estimulante Humana , Quistes del Sistema Nervioso Central/complicaciones , Quistes del Sistema Nervioso Central/diagnóstico por imagen , EstradiolRESUMEN
Diverse paths generated by reactive oxygen species (ROS) can mediate contaminant transformation and fate in the soil/aquatic environments. However, the pathways for ROS production upon the oxygenation of redox-active ferrous iron minerals are underappreciated. Ferrihydrite (Fh) can be reduced to produce Fe(II) by Shewanella oneidensis MR-1, a representative strain of dissimilatory iron-reducing bacteria (DIRB). The microbial reaction formed a spent Fh product named mr-Fh that contained Fe(II). Material properties of mr-Fh were characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). Magnetite could be observed in all mr-Fh samples produced over 1-day incubation, which might greatly favor the Fe(II) oxygenation process to produce hydroxyl radical (â¢OH). The maximum amount of dissolved Fe(II) can reach 1.1 mM derived from added 1 g/L Fh together with glucose as a carbon source, much higher than the 0.5 mM generated in the case of the Luria-Bertani carbon source. This may confirm that MR-1 can effectively reduce Fh and produce biogenetic Fe(II). Furthermore, the oxygenation of Fe(II) on the mr-Fh surface can produce abundant ROS, wherein the maximum cumulative â¢OH content is raised to about 120 µM within 48 h at pH 5, but it is decreased to about 100 µM at pH 7 for the case of MR-1/Fh system after a 7-day incubation. Thus, MR-1-mediated Fh reduction is a critical link to enhance ROS production, and the â¢OH species is among them the predominant form. XPS analysis proves that a conservable amount of Fe(II) species is subject to adsorption onto mr-Fh. Here, MR-1-mediated ROS production is highly dependent on the redox activity of the form Fe(II), which should be the counterpart presented as the adsorbed Fe(II) on surfaces. Hence, our study provides new insights into understanding the mechanisms that can significantly govern ROS generation in the redox-oscillation environment.