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1.
J Environ Sci (China) ; 147: 62-73, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003077

RESUMEN

Non-ferrous metal smelting poses significant risks to public health. Specifically, the copper smelting process releases arsenic, a semi-volatile metalloid, which poses an emerging exposure risk to both workers and nearby residents. To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting, we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks. Results showed that zinc and copper (485.38 and 14.00 µg/L), and arsenic, lead, cadmium, vanadium, tin and antimony (46.80, 6.82, 2.17, 0.40, 0.44 and 0.23 µg/L, respectively) in workers (n=179) were significantly higher compared to controls (n=168), while Zinc, tin and antimony (412.10, 0.51 and 0.15 µg/L, respectively) of residents were significantly higher than controls. Additionally, workers had a higher monomethyl arsenic percentage (MMA%), showing lower arsenic methylation capacity. Source appointment analysis identified arsenic, lead, cadmium, antimony, tin and thallium as co-exposure metal(loid)s from copper smelting, positively relating to the age of workers. The hazard index (HI) of workers exceeded 1.0, while residents and control were approximately at 1.0. Besides, all three populations had accumulated cancer risks exceeding 1.0 × 10-4, and arsenite (AsIII) was the main contributor to the variation of workers and residents. Furthermore, residents living closer to the smelting plant had higher health risks. This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations, providing valuable insights for pollution control in non-ferrous metal smelting.


Asunto(s)
Metalurgia , Exposición Profesional , Humanos , Exposición Profesional/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Metales/orina , Metales/análisis , Medición de Riesgo , Arsénico/análisis , Monitoreo del Ambiente , Adulto , Contaminantes Ambientales/análisis , Persona de Mediana Edad
2.
Biomacromolecules ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956952

RESUMEN

The surface of food processing equipment is easily affected by biofilm-forming bacteria, leading to cross-contamination and food safety hazards. The critical issue is how to endow the surface of contact materials with antibacterial and antibiofilm abilities. A sustainable, stable, and antibiofilm coating was prepared by phase transition of glutenin. The disulfide bonds in glutenin were reduced by tris(2-carboxyethyl)phosphine, triggering the phase transition of glutenin. Hydrophobic interactions and intermolecular disulfide bonds may be the primary forces. Furthermore, the phase-transited products formed a nanoscale coating on the surface of stainless steel and glass under their own adhesion force and gravity. The coating exhibited good stability in harsh environments. More importantly, after 3 h of direct contact, the colony of Escherichia coli and Staphylococcus aureus decreased by one logarithm. The amount of biofilm was observed to be significantly decreased through optical microscopy and scanning electron microscopy. This article provides a foundational module for developing novel coatings.

3.
J Med Chem ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38959216

RESUMEN

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

4.
J Sci Food Agric ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967243

RESUMEN

BACKGROUND: Mycotoxin contamination of food has been gaining increasing attention. Hidden mycotoxins that interact with biological macromolecules in food could make the detection of mycotoxins less accurate, potentially leading to the underestimation of the total exposure risk. Interactions of the mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) with high-molecular glutenin were explored in this study. RESULTS: The recovery rates of AOH and AME (1, 2, and 10 µg kg-1) in three types of grains (rice, corn, and wheat) were relatively low. Molecular dynamics (MD) simulations indicated that AOH and AME bound to glutenin spontaneously. Hydrogen bonds and π-π stacking were the primary interaction forces at the binding sites. Alternariol with one additional hydroxyl group exhibited stronger binding affinity to glutenin than AME when analyzing average local ionization energy. The average interaction energy between AOH and glutenin was -80.68 KJ mol-1, whereas that of AME was -67.11 KJ mol-1. CONCLUSION: This study revealed the mechanisms of the interactions between AOH (or AME) and high-molecular glutenin using MD and molecular docking. This could be useful in the development of effective methods to detect pollution levels. These results could also play an important role in the evaluation of the toxicological properties of bound altertoxins. © 2024 Society of Chemical Industry.

5.
Clin Exp Med ; 24(1): 143, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38960935

RESUMEN

Immune checkpoint inhibitors (ICIs) are approved to treat colorectal cancer (CRC) with mismatch-repair gene deficiency, but the response rate remains low. Value of current biomarkers to predict CRC patients' response to ICIs is unclear due to heterogeneous study designs and small sample sizes. Here, we aim to assess and quantify the magnitude of multiple biomarkers for predicting the efficacy of ICIs in CRC patients. We systematically searched MEDLINE, Embase, the Cochrane Library, and Web of Science databases (to June 2023) for clinical studies examining biomarkers for efficacy of ICIs in CRC patients. Random-effect models were performed for meta-analysis. We pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for biomarkers predicting response rate and survival. 36 studies with 1867 patients were included in systematic review. We found that a lower pre-treatment blood neutrophil-to-lymphocyte ratio (n=4, HR 0.37, 95%CI 0.21-0.67) predicts good prognosis, higher tumor mutation burden (n=10, OR 4.83, 95%CI 2.16-10.78) predicts response to ICIs, and liver metastasis (n=16, OR 0.32, 95%CI 0.16-0.63) indicates resistance to ICIs, especially when combined with VEGFR inhibitors. But the predictive value of tumor PD-L1 expression (n=9, OR 1.01, 95%CI 0.48-2.14) was insignificant in CRC. Blood neutrophil-to-lymphocyte ratio, tumor mutation burden, and liver metastasis, but not tumor PD-L1 expression, function as significant biomarkers to predict efficacy of ICIs in CRC patients. These findings help stratify CRC patients suitable for ICI treatments, improving efficacy of immunotherapy through precise patient management. (PROSPERO, CRD42022346716).


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Inhibidores de Puntos de Control Inmunológico , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Biomarcadores de Tumor/genética , Pronóstico , Resultado del Tratamiento , Neutrófilos , Linfocitos
6.
J Mater Chem B ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949411

RESUMEN

Most existing hydrogels, even recently developed injectable hydrogels that undergo a reversible sol-gel phase transition in response to external stimuli, are designed to gel immediately before or after implantation/injection to prevent the free diffusion of materials and drugs; however, the property of immediate gelation leads to a very weak tumour-targeting ability, limiting their application in anticancer therapy. Therefore, the development of tumour-specific responsive hydrogels for anticancer therapy is imperative because tumour-specific responses improve their tumour-targeting efficacy, increase therapeutic effects, and decrease toxicity and side effects. In this review, we introduce the following three types of tumour-responsive hydrogels: (1) hydrogels that gel specifically at the tumour site; (2) hydrogels that decompose specifically at the tumour site; and (3) hydrogels that react specifically with tumours. For each type, their compositions, the mechanisms of tumour-specific responsiveness and their applications in anticancer treatment are comprehensively discussed.

7.
Singapore Med J ; 65(7): 380-388, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38973187

RESUMEN

ABSTRACT: Ischaemia with no obstructive coronary arteries (INOCA) has been a diagnostic and therapeutic challenge for decades. Several studies have demonstrated that INOCA is associated with an increased risk of death, adverse cardiovascular events, poor quality of life and high healthcare cost. Although there is increasing recognition of this entity in the Western population, in the Asian population, INOCA remains elusive and its prevalence uncertain. Despite its prognostic significance, diagnosis of INOCA is often delayed. In this review, we identified the multiple barriers to its diagnosis and management, and proposed strategies to overcome them.


Asunto(s)
Pueblo Asiatico , Isquemia Miocárdica , Humanos , Isquemia Miocárdica/epidemiología , Calidad de Vida , Pronóstico , Vasos Coronarios , Prevalencia , Factores de Riesgo , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico
8.
BMC Public Health ; 24(1): 1862, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992632

RESUMEN

OBJECTIVE: Previous studies have revealed associations between sleep quality and mental health, yet the comprehensive role of sleep quality, daytime dysfunction, social exclusion, and self-control in difficulties with emotion regulation remains unclear. This study aimed to elucidate how sleep quality affects emotion regulation difficulties among middle school students through pathways involving daytime dysfunction, social exclusion, and self-control, thereby providing a more comprehensive theoretical basis for mental health interventions. METHODS: Utilizing the pittsburgh sleep quality index, the adolescent social exclusion scale, the brief self-control scale, and emotion regulation scale-short form, we assessed 1067 students randomly selected from four middle schools from October to November 2023. After the removal of extreme values (those exceeding 3 standard deviations), 806 students were retained for data analysis. RESULTS: Our findings indicate that poor sleep quality significantly contributes to increased daytime dysfunction(ß = 0.86, SE = 0.07, p < .001), which in turn affects social exclusion(ß = 0.60, SE = 0.16, p < 0 0.001), self-control abilities(ß = 1.27, SE = 0.16, p < .001) and emotion regulation difficulties(ß = 1.56, SE = 0.30, p < .001). Social exclusion mediates the relationship between sleep quality and emotion regulation difficulties(Estimate = 0.11, SE = 0.04, 95% CI [0.04, 0.20] ). CONCLUSION: The aim of this study is to provide new insights into the development of effective intervention measures to improve sleep and mental health in adolescents.


Asunto(s)
Regulación Emocional , Autocontrol , Calidad del Sueño , Humanos , Adolescente , Femenino , Masculino , Autocontrol/psicología , Distancia Psicológica , Análisis de Mediación , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Encuestas y Cuestionarios , Aislamiento Social/psicología
9.
World J Gastrointest Oncol ; 16(6): 2541-2554, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38994140

RESUMEN

BACKGROUND: Stage classification for Siewert II adenocarcinoma of the esophagogastric junction (AEG) treated with neoadjuvant chemotherapy (NAC) has not been established. AIM: To investigate the optimal stage classification for Siewert II AEG with NAC. METHODS: A nomogram was established based on Cox regression model that analyzed variables associated with overall survival (OS) and disease-specific survival (DSS). The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test, Akaike information criterion, Harrell concordance index, time-receiver operating characteristic curve, and decision curve analysis. RESULTS: Data from 725 patients with Siewert type II AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses revealed that sex, marital status, race, ypT stage, and ypN stage were independent prognostic factors of OS, whereas sex, race, ypT stage, and ypN stage were independent prognostic factors for DSS. These factors were incorporated into the OS and DSS nomograms. Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer. Finally, a user-friendly web application was developed for clinical use. CONCLUSION: The nomogram established specifically for patients with Siewert type II AEG receiving NAC demonstrated good prognostic performance. Validation using external data is warranted before its widespread clinical application.

10.
J Environ Manage ; 366: 121532, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38986382

RESUMEN

Injection of an alkaline absorbent into the flue gas can significantly reduce SO2 and SO3 emissions. The article presents alkaline absorbents employed in industrial processes to remove SO2 and SO3 from flue gases, detailing their characteristics and applications across various process conditions. It summarizes the mechanisms and influencing factors behind SO2 and SO3 removal, outlines the impact of multi-component gases, particularly SO2, on SO3 removal in actual flue gases, and elucidates this competitive phenomenon from a theoretical standpoint. The article compares the application scenarios and efficiencies of alkaline absorbents across different processes, identifies the optimal combinations of various absorbents and processes, and proposes a synergistic approach for the removal of SO2 and SO3. The findings demonstrate that by injecting calcium- or sodium-based absorbents into dry processes, SO2 and SO3 can be removed efficiently and cost-effectively, with process optimization and absorbent modifications further enhancing the SOx removal efficiency. In the future, by blending two or more absorbents and applying them to dry processes, a synergistic removal of SO2 and SO3 can be achieved.

11.
Medicine (Baltimore) ; 103(28): e38860, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996164

RESUMEN

The purpose of the current study was to analyze whether aortic calcification had impact on the anastomotic leakage (AL) after rectal cancer (RC) surgery. We collected patients' information from January 2011 to January 2020 in a single teaching hospital. Preoperative computed tomography images were obtained. Abdominal aortic calcification (AAC), superior mesenteric aortic calcification, and inferior mesenteric aortic calcification were recorded. The difference of AL and grade C AL was calculated. A total of 2412 RC patients were included in this study. Ninety-seven (4.0%) RC patients experienced AL and 47 (1.9%) RC patients experienced grade C AL. The amount of AAC, superior mesenteric aortic calcification, and inferior mesenteric aortic calcification was 1546 (64.1%), 128 (5.3%), and 31 (1.3%). The AL group had higher portion of AAC (P = .019) than the no AL group, and the grade C AL group had higher portion of AAC (P = .016) than the no grade C AL group. In univariate logistic regression analysis, AAC was a significant potential factor for AL (P = .021, OR = 1.739, 95% CI = 1.088-2.779) and grade C AL (P = .019, OR = 2.339, 95% CI = 1.115-4.986). However, in multivariate logistic regression, AAC was not an independent predictive factor for AL (P = .157, OR = 1.443, 95% CI = 0.871-2.358) or grade C AL (P = .064, OR = 2.055, 95% CI = 0.960-4.399). AAC was associated with higher amount of AL and grade C AL, however, AAC was not an independent predictive factor for AL or grade C AL.


Asunto(s)
Fuga Anastomótica , Neoplasias del Recto , Calcificación Vascular , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Masculino , Femenino , Fuga Anastomótica/etiología , Fuga Anastomótica/epidemiología , Persona de Mediana Edad , Anciano , Calcificación Vascular/diagnóstico por imagen , Estudios Retrospectivos , Aorta Abdominal/cirugía , Aorta Abdominal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Enfermedades de la Aorta/cirugía , Factores de Riesgo
12.
Front Psychiatry ; 15: 1435394, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045549

RESUMEN

Background: Research from observational studies has demonstrated a link between Alzheimer's disease (AD) and a higher risk of cardiovascular disease (CVD). Uncertainty surrounds the exact genetic cause of AD and coronary heart disease, particularly unstable angina (UA). Mendelian randomization (MR) analysis was used to examine the causal genetic link between AD and UA to evaluate the impact of AD on UA. Methods: The purpose of the bidirectional MR analysis was to investigate the link between exposure and illness causation. Genetic instrumental variables for AD were obtained from European populations using genome-wide association studies (GWAS). The primary causal conclusions were obtained using the inverse variance weighted approach (IVW), and other sensitivity analysis techniques were employed. Sensitivity analyses were carried out to evaluate heterogeneity and horizontal pleiotropy to guarantee accurate MR results. Results: An elevated risk of UA was linked to genetically predicted AD (IVW: OR=3.439, 95% CI: 1.565-7.555, P=0.002). A substantial genetic relationship between UA and the risk of AD was not supported by any evidence in the reverse study (IVW: OR=0.998, 95% CI: 0.995-1.001, P=0.190). Various MR techniques produced consistent results. Sensitivity analysis revealed no discernible heterogeneity or horizontal pleiotropy. Conclusions: One risk factor for UA that we found in our bidirectional Mendelian randomization trial was AD. This highlights the necessity of researching the underlying molecular mechanisms linked to AD and UA as well as the possibility of creating individualized treatment plans based on genetic data.

13.
Lipids Health Dis ; 23(1): 220, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039525

RESUMEN

BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.


Asunto(s)
Estenosis Coronaria , Infarto del Miocardio , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Masculino , Estudios Prospectivos , Infarto del Miocardio/genética , Persona de Mediana Edad , Pronóstico , Estenosis Coronaria/genética , Adulto , Apolipoproteína A-I/genética , Intervención Coronaria Percutánea , Serina Endopeptidasas/genética , Genotipo , Apolipoproteína B-100/genética , Predisposición Genética a la Enfermedad
14.
Nat Commun ; 15(1): 6215, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043664

RESUMEN

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Recurrencia Local de Neoplasia , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Femenino , Recurrencia Local de Neoplasia/genética , Persona de Mediana Edad , Anciano , Pronóstico , Genómica/métodos , Adulto , Estadificación de Neoplasias , Aprendizaje Profundo , Supervivencia sin Enfermedad
15.
Front Oncol ; 14: 1371599, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035744

RESUMEN

With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.

16.
Molecules ; 29(13)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38999130

RESUMEN

Catalyzed by Rh2(esp)2 (10 mol%) and (±)-BINAP (20 mol%) in DCE at 80 °C, the cascade assembly between diazobarbiturates and alkylidene pyrazolones proceeded readily and produced spiro-furopyrimidines in 38-96% chemical yields. The chemical structure of the prepared spirofuro-pyrimidines was firmly confirmed by X-ray diffraction analysis.

17.
J Pharm Biomed Anal ; 248: 116325, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38959755

RESUMEN

The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components-scutellarin and luteolin-which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications.


Asunto(s)
Apigenina , Microbioma Gastrointestinal , Glucuronatos , Luteolina , Scutellaria , Espectrometría de Masas en Tándem , Microbioma Gastrointestinal/efectos de los fármacos , Luteolina/farmacología , Luteolina/metabolismo , Luteolina/farmacocinética , Scutellaria/química , Apigenina/farmacología , Glucuronatos/metabolismo , Humanos , Espectrometría de Masas en Tándem/métodos , Línea Celular Tumoral , Animales , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología , Cromatografía Liquida/métodos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/farmacocinética , Disponibilidad Biológica , Masculino , Biotransformación , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética
18.
Transl Oncol ; 47: 102047, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38972174

RESUMEN

Osteosarcoma, one of the most common primary malignancies in children and adolescents, has the primary characteristics of a poor prognosis and high rate of metastasis. This study used super-enhancer-related genes derived from two different cell lines to construct five novel super-enhancer-related gene prognostic models for patients with osteosarcoma. The training and testing datasets were used to confirm the prognostic models of the five super-enhancer-related genes, which resulted in an impartial predictive element for osteosarcoma. The immunotherapy and prediction of the response to anticancer drugs have shown that the risk signature of the five super-enhancer-related genes positively correlate with chemosensitivity. Furthermore, functional analysis of the risk signature genes revealed a significant relationship between gene groups and the malignant characteristics of tumours. TNF Receptor Superfamily Member 11b (TNFRSF11B) was selected for functional verification. Silencing of TNFRSF11B suppressed the proliferation, migration, and invasion of osteosarcoma cells in vitro and suppressed osteosarcoma growth in vivo. Moreover, transcriptome sequencing was performed on MG-63 cells to study the regulatory mechanism of TNFRSF11B in osteosarcoma cells, and it was discovered that TNFRSF11B is involved in the development of osteosarcoma via the phosphoinositide 3-kinase signalling pathway. Following the identification of TNFRSF11B as a key gene, we selected an inhibitor that specifically targeted this gene and performed molecular docking simulations. In addition, risedronic acid inhibited osteosarcoma growth at both cellular and molecular levels. In conclusion, the super-enhancer-related gene signature is a viable therapeutic tool for osteosarcoma prognosis and treatment.

19.
Proc Natl Acad Sci U S A ; 121(29): e2323040121, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38985761

RESUMEN

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Estomas de Plantas , Transducción de Señal , Fosforilación , Estomas de Plantas/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Dominios Proteicos , Mutación
20.
Food Chem ; 459: 140416, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39024877

RESUMEN

Matrix effects limit the application of surface-enhanced Raman scattering (SERS) technology in the field of food safety. This study elucidated it from the perspective of protein corona by employing a model system for melamine SERS detection in milk. Compared with the melamine standard solution, higher detection limits (1 mg/L and 10 mg/L) are observed in milk matrix. The melamine signal exhibits an 80% reduction in whey protein solution, suggesting that protein has a significant impact on SERS signals. The changes in particle size, zeta potential and UV-vis spectra indicate the AuNPs interact with whey protein. Forming protein corona inhibits the melamine-induced AuNPs aggregation, reducing the number of 'hot spot' and the adsorption of melamine on AuNPs (from 0.28 mg/L to 0.07 mg/L), which may be responsible for signal loss. The found matrix effect from protein corona provides new insights for developing strategies about reducing matrix effect in SERS application.

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