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Recent studies have shown that microRNA-16-5p (miR-16-5p) plays a crucial role in the pathological mechanism of vascular calcification. Nevertheless, the expression profile of miR-16-5p in maintenance hemodialysis (MHD) patients who are predisposed to vascular calcification remains unknown. This study aims to investigate the potential associations between calcification risk and serum miR-16-5p expression among MHD patients. This cross-sectional study involved 132 MHD patients from the Dialysis Center of Beijing Friendship Hospital between 1 January 2019 and 31 December 2020. The degree of calcification in MHD patients was assessed using the Abdominal aortic calcification (AAC) score, and miR-16-5p expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) with the 2-ΔΔCT method. Statistical analyses, including spearman correlation, linear regression and logistic regression analysis were used to explore the associations between laboratory parameters and AAC score. Calcifications were observed in 79(59.80%) patients. The linear regression showed a one-quartile decrease in miR-16-5p expression led to a significant increase in the AAC score by 5.336 (95% CI: 2.670-10.662, p = 0.000). Multivariate logistic regression analyses revealed that decreased miR-16-5p expression, reduced serum urea nitrogen, elevated white blood cell count, and longer dialysis vintage were significantly associated with an increased incidence of vascular calcification. The Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) of the miR-16-5p-based logistic regression model was 0.842 (95% CI: 0.771-0.913, p = 0.000). There was an independent association between miR-16-5p expression and calcification degree. Lower miR-16-5p expression levels seem to be a potential risk factor of vascular calcification in MHD patients.
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Aorta Abdominal , MicroARNs , Diálisis Renal , Calcificación Vascular , Humanos , MicroARNs/sangre , Masculino , Femenino , Diálisis Renal/efectos adversos , Calcificación Vascular/sangre , Calcificación Vascular/etiología , Persona de Mediana Edad , Aorta Abdominal/patología , Aorta Abdominal/diagnóstico por imagen , Estudios Transversales , Anciano , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Curva ROC , Factores de Riesgo , Modelos LogísticosRESUMEN
The recovery of precious metals (PMs) from secondary resources has garnered significant attention due to environmental and economic considerations. Covalent organic frameworks (COFs) have emerged as promising adsorbents for this purpose, owing to their tunable pore size, facile functionalization, exceptional chemical stability, and large specific surface area. This review provides an overview of the latest research progress in utilizing COFs to recover PMs. Firstly, the design and synthesis strategies of chemically stable COF-based materials, including pristine COFs, functionalized COFs, and COF-based composites, are delineated. Furthermore, the application of COFs in the recovery of gold, silver, and platinum group elements is delved into, emphasizing their high adsorption capacity and selectivity as well as recycling ability. Additionally, various interaction mechanisms between COFs and PM ions are analyzed. Finally, the current challenges faced by COFs in the field of PM recovery are discussed, and potential directions for future development are proposed, including enhancing the recyclability and reusability of COF materials and realizing the high recovery of PMs from actual acidic wastewater. With the targeted development of COF-based materials, the recovery of PMs can be realized more economically and efficiently in the future.
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Cisplatin (DDP) resistance poses a significant challenge in the treatment of ovarian cancer. Studies have shown that the combination of certain polysaccharides derived from plants with DDP is an effective approach to overcoming drug resistance in some cancers. Angelica sinensis (Oliv.) Diels has been used for centuries in China to treat gynecological ailments. Numerous studies indicate that Angelica sinensis polysaccharide (ASP), an extract from Angelica sinensis, can inhibit various forms of cancer. However, the impact of ASP on ovarian cancer remains unexplored. Through both in vitro and in vivo experiments, our study revealed the capability of ASP to effectively reversing DDP resistance in cisplatin-resistant ovarian cancer cells, while exhibiting acceptable safety profiles in vivo. To elucidate the mechanism underlying drug resistance reversal, we employed RNA-seq analysis and identified GPX4 as a key gene. Considering the role of GPX4 in ferroptosis, we conducted additional research to explore the effects of combining ASP with DDP on SKOV3/DDP cells. In summary, our findings demonstrate that the combination of ASP and DDP effectively suppresses GPX4 expression in SKOV3/DDP cells, thereby reversing their resistance to DDP.
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Angelica sinensis , Cisplatino , Resistencia a Antineoplásicos , Ferroptosis , Neoplasias Ováricas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Polisacáridos , Cisplatino/farmacología , Femenino , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Ferroptosis/efectos de los fármacos , Polisacáridos/farmacología , Angelica sinensis/química , Línea Celular Tumoral , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Animales , Ratones Desnudos , Ratones , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antineoplásicos/farmacologíaRESUMEN
Vascular calcification (VC) is highly prevalent in patients undergoing hemodialysis, and is a significant contributor to the mortality rate. Therefore, biomarkers that can accurately predict the onset of VC are urgently required. Our study aimed to investigate serum miR-15a levels in relation to VC and to develop a predictive model for VC in patients undergoing hemodialysis at the Beijing Friendship Hospital hemodialysis center between 1 January 2019 and 31 December 2020. The patients were categorized into two groups: VC and non-VC. Logistic regression (LR) models were used to examine the risk factors associated with VC. Additionally, we developed an miR-15a-based nomogram based on the results of the multivariate LR analysis. A total of 138 patients under hemodialysis were investigated (age: 58.41 ± 13.22 years; 54 males). VC occurred in 79 (57.2%) patients. Multivariate LR analysis indicated that serum miR-15a, age, and WBC count were independent risk factors for VC. A miR-15a-based nomogram was developed by incorporating the following five predictors: age, dialysis vintage, predialysis nitrogen, WBC count, and miR-15a. The receiver operating characteristic (ROC) curve had an area under the curve of 0.921, diagnostic threshold of 0.396, sensitivity of 0.722, and specificity of 0.932, indicating that this model had good discrimination. This study concluded that serum miR-15a levels, age, and white blood cell (WBC) count are independent risk factors for VC. A nomogram constructed by integrating these risk factors can be used to predict the risk of VC in patients undergoing hemodialysis.
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MicroARNs , Calcificación Vascular , Masculino , Humanos , Persona de Mediana Edad , Anciano , Diálisis Renal/efectos adversos , Calcificación Vascular/diagnóstico , Calcificación Vascular/etiología , Factores de Riesgo , BiomarcadoresRESUMEN
The extraction performance of materials is highly related to their physical structure. However, the precise impact of ordered pore structure in covalent organic frameworks (COFs) on extraction performance are still puzzling. To look insight into this, a series of COFs with varying degrees of ordered pore structures were prepared at room temperature by adjusting reaction time and their extraction efficiencies toward phenolic compounds were investigated. The experimental results revealed that the COF with a short range ordered pore structure exhibited a higher affinity for phenolic compounds along with a larger enrichment factor, while the COF with a long range ordered pore structure demonstrated faster extraction kinetics. The investigation into interaction mechanism revealed that the density of available sites is responsible for these differences. Taking COF-OMe-0.5 h as solid-phase microextraction fiber coating, a highly efficient and sensitive quantitative analysis method for phenolic compounds was established by combining it with gas chromatograph-mass spectrometer. The established method boasts high enrichment factors (7192-29440), wide linear ranges (2.0-10000 ng L-1), and low detection limits (0.24-0.54 ng L-1). This study provides a conceptual guide for constructing desirable COFs with controlled pore structures for specific applications.
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Artemisia annua L. (A. annua), a Traditional Chinese Medicine (TCM) that has been utilized in China for centuries, is known for its potential anticancer properties. However, the main components and mechanism of action of A. annua on endometrial carcinoma have not been reported. We used the TCMSP database to identify the active components of A. annua and their corresponding gene targets. We then obtained the gene targets specific to endometrial cancer from The Cancer Genome Atlas (TCGA) and GeneCards databases. The gene targets common to three databases were selected, and a "component-target" network was constructed. Protein-protein interaction (PPI) network analysis and ranking of the target proteins identified the key protein PTGS2 network analysis, and ranking of the target proteins identified the key protein PTGS2. We also screened the active components of A. annua and found that quercetin, kaempferol, luteolin, isorhamnetin, artemisin, and stigmasterol had the most targets. Molecular docking models were established for these six components with PTGS2, revealing strong binding activity for all of them. Finally, we conducted validation experiments to assess the effects of quercetin, an active component of A. annua, on endometrial cancer cells (HEC-1-A and Ishikawa cells). Our findings demonstrate that quercetin has the potential to inhibit both cell growth and migration, while also suppressing the expression of PTGS2.
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Solid-phase microextraction (SPME) is a green, environmentally friendly, and efficient technique for sample pre-treatment. Covalent organic frameworks (COFs), a class of porous materials formed by covalent bonds, have gained prominence owing to their remarkable attributes, including large specific surface area, tunable pore size, and robust thermal/chemical stability. These characteristics have made COFs highly appealing as potential coatings for SPME fiber over the past decades. In this review, various methods used to prepare SPME coatings based on COFs are presented. These methods encompass physical adhesion, sol-gel processes, in situ growth, and chemical cross-linking strategies. In addition, the applications of COF-based SPME coating fibers for the preconcentration of various targets in environmental, food, and biological samples are summarized. Moreover, not only their advantages but also the challenges they pose in practical applications are highlighted. By shedding light on these aspects, this review aims to contribute to the continued development and utilization of COF materials in the field of sample pretreatment.
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Identification of translocator protein-related genes involved in bensulfuron-methyl (BSM) uptake and transport in rice could facilitate the development of herbicide-tolerant cultivars by inactivating them. This study found that the OsCNGC12 mutants not only reduced BSM uptake but also compromised the Ca2 ⺠efflux caused by BSM in the roots, regulating dynamic equilibrium of Ca2 ⺠inside the cell and conferring non-target-site tolerance to BSM.
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Herbicidas , Oryza , Herbicidas/farmacología , Plantones/genética , CalcioRESUMEN
BACKGROUND: The effectiveness of multitarget combination therapy with a corticosteroid, cyclosporine and mycophenolate mofetil for idiopathic membranous nephropathy (IMN) is unclear. In the present study, we aimed to compare the efficacy and safety of multitarget therapy with a cyclical corticosteroid-cyclophosphamide regimen in patients with IMN. METHODS: This was a single-centre, prospective, randomized, controlled trial. We randomly assigned patients with IMN to receive multitarget therapy (a combination of prednisone, cyclosporine and mycophenolate mofetil) or 6-month cyclical treatment with a corticosteroid and cyclophosphamide. The study patients were followed up for 12 months. The primary outcome was a composite of complete or partial remissions at 12 months. Adverse events were also assessed. RESULTS: The study cohort comprised 78 patients, 39 of whom received multitarget therapy and the other 39 cyclical alternating treatment with a corticosteroid and cyclophosphamide. At 12 months, 31 of 39 patients (79%) in the multitarget therapy group and 34 of 39 (87%) in the corticosteroid-cyclophosphamide group had achieved complete or partial remissions (relative risk 0.93; 95% confidence interval 0.72-1.21; P = .85; log-rank test). The prevalence of adverse events was significantly lower in the multitarget therapy group than in the corticosteroid-cyclophosphamide group [46% (18 of 39) vs 74% (29 of 39); P < .05]. CONCLUSIONS: Multitarget therapy for IMN patients is noninferior to cyclical alternating treatment with corticosteroid and cyclophosphamide in inducing proteinuria remission and has a better safety profile than the corticosteroid-cyclophosphamide combination.
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Ciclosporina , Glomerulonefritis Membranosa , Humanos , Ciclosporina/uso terapéutico , Ácido Micofenólico/uso terapéutico , Inmunosupresores/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Estudios Prospectivos , Ciclofosfamida/uso terapéutico , Corticoesteroides/uso terapéutico , Quimioterapia CombinadaRESUMEN
Cardiovascular events among patients with chronic kidney disease (CKD) are associated with vascular calcification (VC). Nevertheless, the process of vascular calcification is complicated. A mechanism of VC is cellular osteogenic transdifferentiation. The mechanism through which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) relieve VC is unknown. For the purpose of this study, we used human aortic vascular smooth muscle cells (HA-VSMCs) stimulated by high phosphate to investigate how BMSC-Exo works. Cell calcification was detected by Alizarin red S staining, AKP activity analysis, and the Ca2+ concentration test. The dual-luciferase reporter gene assays were utilized to confirm the targeting link between miR-15a-5p, miR-15b-5p, and miR-16-5p (miR-15a/15b/16) and nuclear factors of activated T cells 3 (NFATc3). The expression of osteogenic transdifferentiation biomarkers was detected using Western blot and RT-qPCR. Based on our findings, miR-15a/15b/16 plays a crucial role in BMSC-Exo's inhibitory effects on calcification and osteogenic transdifferentiation. We then confirmed that miR-15a/15b/16 specifically target the 3'UTR of NFATc3 mRNA and that three miRNAs are more effective than one miRNA. Moreover, we found that down-regulation of NFATc3 could inhibit osteocalcin (OCN) expression, thereby inhibiting the osteogenic transdifferentiation and calcification of HA-VSMCs. This study found that BMSC-Exo plays a role in calcification inhibition by transferring miR-15a/15b/16 and inhibiting their common target gene NFATc3, which down-regulates OCN expression and thus inhibits HA-VSMC osteogenic transdifferentiation. This study identifies a novel target for therapeutic therapy of CKD-VC.
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Exosomas , Células Madre Mesenquimatosas , MicroARNs , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Exosomas/metabolismo , Músculo Liso Vascular , Osteocalcina/metabolismo , MicroARNs/metabolismo , Miocitos del Músculo Liso/metabolismo , Osteogénesis/genética , Calcificación Vascular/genética , Calcificación Vascular/metabolismo , Insuficiencia Renal Crónica/metabolismo , Células de la Médula Ósea , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismoRESUMEN
Vascular calcification (VC) and myocardial hypertrophy are very common in patients on hemodialysis (HD). Previous studies have only assessed the cross-sectional associations of VC with left ventricular mass (LVM) and the predictive value of individual factors. The present study investigated the relationship between abdominal aortic calcification (AAC) and LVM increment over time, and the combined effect of these factors on the outcomes of HD patients. 104 HD patients were enrolled. AAC scores were evaluated on left lateral lumbar spine radiographs. Echocardiography was performed to calculate the LVM changes during a 2-year period. At baseline, 91 patients (87.5%) had varying degrees of AAC (median score 6.0, range 2.0 - 11.0). After 2 years, the mean LVM change was 7.49 g (range -5.03 - 26.00 g), and 68 patients (65%) had an increased LVM. Patients with higher baseline AAC scores had significantly larger LVM and LVM index increments. Patients with increased LVM had significantly higher baseline AAC scores and hemoglobin, serum phosphate, and hypersensitive C-reactive protein levels. Multiple stepwise linear regression demonstrated that the baseline AAC was the only independent predictor of increased LVM after 2 years. 28 patients (26.9%) died in the subsequent 5 years. Patients with lower baseline AAC scores had a significantly higher cumulative survival rate than those with higher AAC scores. However, the LVM change (either alone or in combination with the AAC score) had no significant effect on survival. In conclusion, AAC is an independent predictor of LVM increase over time in HD patients. Prevention and treatment of VC may be a promising intervention target to improve left ventricular remodeling and outcomes in HD patients.
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Proteína C-Reactiva , Calcificación Vascular , Aorta Abdominal/diagnóstico por imagen , Estudios Transversales , Humanos , Fosfatos , Pronóstico , Diálisis Renal/efectos adversos , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/etiologíaRESUMEN
This study aimed to synthesize silica-coated gold (Au@SiO2) nanoparticles coupled to antibodies against the scavenger receptor class B type I (SR-BI) and investigate their potential ability of visual tracking and treatment of cervical cancer. The fluorescein isothiocyanate (FITC)-labeled Au@SiO2-SR-BI antibody was synthesized, followed by characterization determination. The expression and location of SR-BI protein in cervical cancer cells were respectively detected by western blot and immunofluorescence assays. The effects of nanoparticles on cancer cells were determined by adsorption assay and apoptosis detection, respectively. The effects of nanoparticles on tumor formation in nude mice were determined. The particle sizes of Au@SiO2 ranged from 2-2.5 µm, and the particle size distribution was relatively uniform. MS751 showed the highest expression of SR-BI. SR-BI was located in the cytomembrane. There were more FITC-Au@SiO2-SR-BI nanoparticles on the surface of the cells compared to FITC-Au@SiO2. Significant apoptosis was observed in the FITC-Au@SiO2-SR-BI-treated group in both MS751 and H8 cells. Photothermal ablation of solid tumors was observed when FITC-Au@SiO2-SR-BI was activated using 808 nm wave. Expressions of the apoptosis-related markers including BCL2, BCLX, and p-AKT were significantly decreased, while those of caspase 3 and caspase 8 were significantly increased. The study presented a novel antibody-conjugated Au@SiO2 nanoparticle specifically targeting molecular receptors on cancer cell membranes. Antibody-conjugated Au@SiO2 nanoparticles may have therapeutic potential for the treatment of cervical cancer.
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Vascular calcification (VC) is a significant complication of chronic kidney disease (CKD) and cellular apoptosis is one of the intricate mechanisms of VC. Bone marrow mesenchymal stem cell-derived exosome (BMSC-Exo) alleviates VC, but the mechanism remains unclear. We investigated the mechanism of BMSC-Exo using high phosphate stimulated Human aortic smooth muscle cells (HA-VSMCs) and 5/6 subtotal nephrectomy (SNx) rat models. We demonstrated that the effect of BMSC-Exo on the inhibition of cellular apoptosis and calcification partially depended on exosomal microRNA-381-3p (miR-381-3p) both in vivo and in vitro, and confirmed that miR-381-3p could inhibit Nuclear Factor of Activated T cells 5 (NFAT5) expression by directly binding to its 3' untranslated region. Additionally, we found that severe calcification of arteries in dialysis patients was associated with decreased miR-381-3p and increased NFAT5 expression levels. Collectively, our findings proved that BMSC-Exo plays anti-calcification and anti-apoptosis roles in CKD by delivering enclosed miR-381-3p, which directly targets NFAT5 mRNA, and leads to a better understanding of the mechanism of CKD-VC.
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Exosomas , Células Madre Mesenquimatosas , MicroARNs , Insuficiencia Renal Crónica , Calcificación Vascular , Regiones no Traducidas 3' , Animales , Exosomas/genética , Exosomas/metabolismo , Femenino , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Insuficiencia Renal Crónica/metabolismo , Factores de Transcripción/metabolismo , Calcificación Vascular/genética , Calcificación Vascular/metabolismoRESUMEN
Vascular calcification is one of the most common complications of chronic kidney disease (CKD), which is closely associated with increased mortality and morbidity rates of CKD patients. It has been reported that increased parathyroid hormone (PTH) aggravates vascular calcification in CKD patients. However, the direct role of PTH in vascular smooth muscle cells (VSMCs) is less elucidated. Here, we present evidence that PTH promotes apoptosis of VSMCs and endoplasmic reticulum (ER) stress participates in this process. Human aorta vascular smooth muscle cells (HASMCs) were treated with different concentrations of PTH for various time. HASMC apoptosis was detected by flow cytometry. Expression of phosphorylated (p)-PERK, CHOP, IRE1, p-JNK, and cleaved caspase 3 was determined by Western blotting. We found that PTH induced HASMC apoptosis and increased the expression of cleaved caspase 3. Furthermore, PTH activated PERK-CHOP and IRE1-JNK ER stress pathways. Either inhibition of JNK by SP600125 or CHOP by siRNA ameliorated PTH-induced apoptosis in HASMCs. We therefore suggest that ER stress participates in PTH-induced apoptosis of VSMCs, which may be a possible mechanism of PTH-promoted vascular calcification in CKD patients.
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Aorta/metabolismo , Apoptosis , Estrés del Retículo Endoplásmico , Miocitos del Músculo Liso/metabolismo , Hormona Paratiroidea/metabolismo , Calcificación Vascular/metabolismo , Factor de Transcripción Activador 4/metabolismo , Antracenos/farmacología , Aorta/patología , Células Cultivadas , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fosforilación , ARN Interferente Pequeño/metabolismo , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Calcificación Vascular/patologíaRESUMEN
BACKGROUND: Exosomes can be secreted from bone marrow mesenchymal stem cells (BMSCs) to extracellular space and exert anti-fibrotic effects, but the underlying mechanisms remain to be elucidated. METHODS: 5/6 subtotal nephrotomy (SNx) rat models and TGF-ß1-induced human renal proximal tubular epithelial cells (HRPTEpiCs) were established to simulate renal fibrosis. Renal function and fibrosis were assessed by Hematoxylin and Eeosin (HE) staining, Masson staining, immunohistochemistry, and western blot. The expression of Smad 7/Smurf 2 was detected in rats and HRPTEpiCs by western blot, and a further potential mechanism was explored using si-Smurf 2. RESULTS: BMSC-Exo improved renal function, reduced the fibrotic region, down-regulated the expression of fibronectin, Collagen-I, α-SMA, and up-regulated E-cadherin in SNx models. In vitro study demonstrated that knocking down the expression of Smurf 2 significantly increased the expression of Smad 7, which could be enhanced by BMSC-Exo. BMSC-Exo could alleviate the fibrosis induced by TGF-ß1 in tubular epithelial cells and enhanced the protective effect of si-Smurf 2 on renal fibrosis. CONCLUSIONS: BMSC-Exo inhibited renal fibrosis both in vivo and in vitro, partially, by regulating the Smurf 2/Smad 7 axis. BMSC-Exo enhanced the protective effect of si-Smurf 2 on fibrosis induced by transforming growth factor-ß1 (TGF-ß1).
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Exosomas , Enfermedades Renales , Células Madre Mesenquimatosas , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Transición Epitelial-Mesenquimal , Exosomas/metabolismo , Fibrosis , Enfermedades Renales/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratas , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
PURPOSE: The variation in inflammation in chronic obstructive pulmonary disease (COPD) between individuals is genetically determined. This study aimed to identify gene signatures of COPD through bioinformatics analysis based on multiple gene sets and explore their immune characteristics and transcriptional regulation mechanisms. METHODS: Data from four microarrays were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) between COPD patients and controls. Weighted gene co-expression network analysis was applied to identify trait-related modules and then select key module-related DEGs. The optimized gene set of signatures was obtained using the least absolute shrinkage and selection operator (LASSO) regression analysis. The CIBERSORT algorithm and Pearson correlation test were used to analyze the relationship between gene signatures and immune cells. Finally, public databases were used to predict the transcription factors (TFs) and upstream miRNAs. RESULTS: A total of 127 DEGs in COPD were identified from the combined dataset. By considering the intersection of DEGs and genes in two trait-related modules, 83 key module-related DEGs were identified, which were mainly enriched in interleukin-related pathways. Seven-gene signatures, including MTHFD2, KANK3, GFPT2, PHLDA1, HS3ST2, FGG, and RPS4Y1, were further selected using the LASSO algorithm. These gene signatures showed the predictive potential for COPD risks and were significantly correlated with 18 types of immune cells. Finally, nine miRNAs and three TFs were predicted to target MTHFD2, GFPT2, PHLDA1, and FGG. CONCLUSION: We proposed the seven-gene-signature to predict COPD risk and explored its potential immune characteristics and regulatory mechanisms.
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MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , Proteínas Portadoras , Biología Computacional , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , MicroARNs/genética , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genéticaRESUMEN
MOF-derived zink and nitrogen co-doped porous carbon (ZNPC) was synthesized through the pyrolysis of MOF-5-NH2 and used as a solid-phase microextraction (SPME) coating material. Coupled with gas chromatography-mass spectrometry (GC-MS), headspace SPME (HS-SPME) based on ZNPC was adopted for the determination of phenols in food samples. The co-existence of N and Zn in ZNPC endows the derived carbon superior hydrophilicity, which is highly beneficial for phenols capture. After optimizing the conditions of extraction and desorption, a sensitive analytical method was established with low limits of detections (LODs, 0.73-2.3 ng g-1) and wide linear ranges (5-5000 ng g-1). Both the intra-fiber repeatability (RSDs from 2.8-7.3%) and inter-fiber reproducibility (RSDs from 9.7-11.7%) were satisfactory. The established method was applied to phenol determination in beef jerky and duck neck with satisfactory recoveries of 81.2-120.4% and RSDs of 2.8-9.9%, which met well with the requirement of practical application.
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Our previous study showed that bone marrow mesenchymal stem cell derived exosomes (BMSC-Exos) suppress high phosphorus (Pi)-induced calcification of vascular smooth muscle cells (VSMCs). However, the mechanism had remained unclear. This study aimed to investigate the mechanism by which BMSC-Exos inhibit vascular calcification (VC). We found that BMSC-Exos reduced high Pi-induced Runx2, osteocalcin and BMP2 expression and inhibited the calcium deposition. Gene expression of human VSMCs stimulated by Pi or Pi plus BMSC-Exos (Pi + Exo) was systematically examined by microarray technology. NONHSAT 084969.2 and transcription factor p65 expression was significantly lower in the Pi + Exo group compared with the Pi group. This finding indicated that NONHSAT 084969.2 and the nuclear factor-κB pathway might play an important role in VC inhibition by BMSC-Exos. By silencing NONHSAT 084969.2 with small interfering RNA, Runx2, BMP2, and osteocalcin expression was decreased significantly. The calcified nodule content and alkaline phosphatase activity were reduced after NONHSAT 084969.2 inhibition and p65, p50, and IκB kinase-α expression was decreased significantly. These results indicated that BMSC-Exos inhibited Pi-induced transdifferentiation and calcification of VSMCs by regulating the NONHSAT 084969.2/nuclear factor-κB axis.
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Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , FN-kappa B/metabolismo , Fósforo/toxicidad , ARN Largo no Codificante/metabolismo , Calcificación Vascular/genética , Línea Celular , Transdiferenciación Celular/efectos de los fármacos , Análisis por Conglomerados , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Exosomas/ultraestructura , Perfilación de la Expresión Génica , Humanos , Minerales/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Calcificación Vascular/patologíaRESUMEN
PURPOSE: Cervical cancer remains a major cause of cancer-related death in women, especially in developing countries. Previously, we found that the acetylation levels of chloride intracellular channel 1 (CLIC1) at lysine 131 were increased in cervical cancer tissues using a label-free proteomics approach. The aim of this study was to further determine the role of CLIC1 expression and its acetylation in cervical cancer. METHODS: CLIC1 expression and its implications for the prognosis of cervical cancer were analyzed using primary patient samples and cells, and the Gene Expression Profiling Interactive Analysis (GEPIA) database (gepia.cancer-pku.cn). The effect of CLIC1 on cervical cancer cells was evaluated using Cell Counting Kit (CCK)-8, flow cytometry, scratch wound healing, transwell, Western blotting and co-immunoprecipitation (Co-IP) assays. In vivo tumor growth was assessed using mouse xenograft models. RESULTS: We found that CLIC1 expression was increased in cervical cancer tissues and cells and that patients with a high CLIC1 expression tended to have a shorter overall survival time. Knockdown of CLIC1 significantly reduced in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumorigenesis. At the molecular level, we found that nuclear factor kappa B (NF-κB) activity was positively regulated by CLIC1. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, attenuated the tumor-promoting effect of CLIC1. Moreover, we found that CLIC1 acetylation at K131 was upregulated in cervical cancer cells, which stabilized CLIC1 by inhibiting its ubiquitynation. Substitution of K131 inhibited CLIC1 ubiquitynation and promoted in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumor growth. In addition, we found that acetyltransferase HAT1 was responsible for CLIC1 acetylation at K131. CONCLUSION: Our data indicate that CLIC1 acts as a tumor promoter in cervical cancer, suggesting a potential treatment strategy for cervical cancer by regulating CLIC1 expression and/or acetylation.