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1.
J Transl Med ; 22(1): 103, 2024 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-38273371

RESUMEN

BACKGROUND: Lymph node metastasis (LNM) is a prognostic biomarker and affects therapeutic selection in colorectal cancer (CRC). Current evaluation methods are not adequate for estimating LNM in CRC. H&E images contain much pathological information, and collagen also affects the biological behavior of tumor cells. Hence, the objective of the study is to investigate whether a fully quantitative pathomics-collagen signature (PCS) in the tumor microenvironment can be used to predict LNM. METHODS: Patients with histologically confirmed stage I-III CRC who underwent radical surgery were included in the training cohort (n = 329), the internal validation cohort (n = 329), and the external validation cohort (n = 315). Fully quantitative pathomics features and collagen features were extracted from digital H&E images and multiphoton images of specimens, respectively. LASSO regression was utilized to develop the PCS. Then, a PCS-nomogram was constructed incorporating the PCS and clinicopathological predictors for estimating LNM in the training cohort. The performance of the PCS-nomogram was evaluated via calibration, discrimination, and clinical usefulness. Furthermore, the PCS-nomogram was tested in internal and external validation cohorts. RESULTS: By LASSO regression, the PCS was developed based on 11 pathomics and 9 collagen features. A significant association was found between the PCS and LNM in the three cohorts (P < 0.001). Then, the PCS-nomogram based on PCS, preoperative CEA level, lymphadenectasis on CT, venous emboli and/or lymphatic invasion and/or perineural invasion (VELIPI), and pT stage achieved AUROCs of 0.939, 0.895, and 0.893 in the three cohorts. The calibration curves identified good agreement between the nomogram-predicted and actual outcomes. Decision curve analysis indicated that the PCS-nomogram was clinically useful. Moreover, the PCS was still an independent predictor of LNM at station Nos. 1, 2, and 3. The PCS nomogram displayed AUROCs of 0.849-0.939 for the training cohort, 0.837-0.902 for the internal validation cohort, and 0.851-0.895 for the external validation cohorts in the three nodal stations. CONCLUSIONS: This study proposed that PCS integrating pathomics and collagen features was significantly associated with LNM, and the PCS-nomogram has the potential to be a useful tool for predicting individual LNM in CRC patients.


Asunto(s)
Colágeno , Neoplasias Colorrectales , Humanos , Metástasis Linfática , Calibración , Nomogramas , Ganglios Linfáticos , Microambiente Tumoral
2.
Genomics ; 115(6): 110744, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37972907

RESUMEN

BACKGROUND: Bariatric surgery (BS) is an effective approach in treating obesity and ameliorating T2DM with obesity. Our previous studies demonstrated that duodenal-jejunal bypass (DJB) altered long non-coding RNAs (lncRNAs) in the gastrointestinal system, which is associated with modulation of lipid metabolism, and glycemic control through entero-pancreatic axis and gut-brain axis. The adipose non-coding RNA expression profile and the underlying competing endogenous RNA (ceRNA) regulatory network pattern post DJB needs further research and investigation. RESULTS: In this study, we compared the lncRNAs, circular RNAs (circRNAs) and messenger RNAs (mRNAs) expression in adipose tissues between the sham group and the DJB group. 2219 differentially expressed mRNAs (DEmRNAs), 722 differential expression of lncRNAs (DElncRNAs) and 425 differential expression of circRNAs (DEcircRNAs) were identified. GO terms and KEGG pathways analysis of the DEmRNAs implied that the dysregulated adipose mRNAs were associated with lipid, amino acid metabolism, insulin resistance, and extra cellular matrix (ECM)-related pathways. Moreover, via analyzing ceRNA regulatory networks of DElncRNAs and DEcircRNAs, 31 hub DE mRNAs, especially Mpp7, 9330159F19Rik, Trhde. Trdn, Sorbs2, were found on these pathways. CONCLUSIONS: The role of DJB in adipose tends to remodel ECM and improve the energy metabolism through the ceRNA regulatory network.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Endógeno Competitivo , ARN Circular/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Obesidad , Redes Reguladoras de Genes
3.
J Sep Sci ; 45(22): 4039-4051, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36084259

RESUMEN

Poria cocos is an edible fungus used as a health product and traditional Chinese medicinal preparation. Nevertheless, little is known about its nutrients. In this study, ultra-high performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry was conducted to quantify nucleosides, nucleobases, and amino acids in 32 batches of Poria cocos samples collected from Anhui, Sichuan, Hubei, Hunan, and Guizhou. Subsequently, the linearity, precision, repeatability, stability, and recovery of our methods were validated. Samples from different regions were clearly separated by partial least squares discriminant analysis and cluster analysis. Our results suggested that Poria cocos samples from different geographical environments differed in nucleosides, nucleobases, and amino acids. The plot of variable importance for projection disclosed differential compositions of L-Leucine, Uridine, L-Asparagine, L-Glutamine, L-phenylalanine, L-Ornithine monohydrochloride, L-Hydroxyproline, Taurine, and Inosine in Poria cocos from five regions. We found the highest content of total analytes, total amino acids, and total non-essential amino acids in Poria cocos from Anhui, total essential amino acids in the Sichuan samples, and total nucleosides in the Hunan samples. Overall, we determined the content of Poria cocos-derived nucleosides, nucleobases, and amino acids, providing the foothold for further chemical mining and use of Poria cocos.


Asunto(s)
Poria , Wolfiporia , Wolfiporia/química , Espectrometría de Masas en Tándem/métodos , Nucleósidos/análisis , Aminoácidos/análisis , Análisis de Componente Principal , Cromatografía Líquida de Alta Presión/métodos , Nutrientes/análisis , Poria/química
4.
Zhongguo Zhong Yao Za Zhi ; 47(10): 2584-2596, 2022 May.
Artículo en Zh | MEDLINE | ID: mdl-35718476

RESUMEN

As a famous and precious Chinese medicinal material, Panax notoginseng(PN) has been commonly used for a long history in China. As reported, PN exhibits significant pharmacological actions in protecting cardiocerebral vascular system and nervous system and suppressing tumors. In recent years, with the innovation in ideas, as well as the development of methods and equipment, PN has been extensively investigated, and notable progress has been made. This paper reviewed the advancements of PN in recent five years from chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology, in which the application of PN extracts in quality control was first summarized. The present study aims to provide a theoretical basis for quality control, product development, and rational medication of PN.


Asunto(s)
Medicamentos Herbarios Chinos , Panax notoginseng , China , Medicamentos Herbarios Chinos/uso terapéutico , Panax notoginseng/química , Control de Calidad
5.
Sensors (Basel) ; 21(21)2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34770469

RESUMEN

Heart rate is one of the most important diagnostic bases for cardiovascular disease. This paper introduces a deep autoencoding strategy into feature extraction of electrocardiogram (ECG) signals, and proposes a beat-to-beat heart rate estimation method based on convolution autoencoding and Gaussian mixture clustering. The high-level heartbeat features were first extracted in an unsupervised manner by training the convolutional autoencoder network, and then the adaptive Gaussian mixture clustering was applied to detect the heartbeat locations from the extracted features, and calculated the beat-to-beat heart rate. Compared with the existing heartbeat classification/detection methods, the proposed unsupervised feature learning and heartbeat clustering method does not rely on accurate labeling of each heartbeat location, which could save a lot of time and effort in human annotations. Experimental results demonstrate that the proposed method maintains better accuracy and generalization ability compared with the existing ECG heart rate estimation methods and could be a robust long-time heart rate monitoring solution for wearable ECG devices.


Asunto(s)
Electrocardiografía , Dispositivos Electrónicos Vestibles , Algoritmos , Análisis por Conglomerados , Frecuencia Cardíaca , Humanos , Distribución Normal , Procesamiento de Señales Asistido por Computador
6.
Bioorg Chem ; 100: 103941, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32450387

RESUMEN

The chemical constituents of the roots and bark of Azadirachta indica were investigated, leading to the isolation of six tricyclic diterpenoids and four limonoids including a new compound, azadirachtin J (4). The structures were elucidated on the basis of NMR spectroscopic techniques, mass spectrometry as well as comparison with the literature. Furthermore, melanogenesis-inhibitory activities of the isolated compounds were evaluated. As a result, compounds 1-3 and 10 exhibited superior inhibitory activities against melanogenesis with no, or almost no, toxicity to the cells (86.5-105.1% cell viability). Western blot analysis showed that compounds 1 and 3 exhibited melanogenesis inhibitory activities in α-MSH-stimulated B16 melanoma cells due to, at least in part, inhibition of the expression of MITF, followed by a decrease in the expression of tyrosinase, TRP-1, and TRP-2. Compounds 1 and 3 exhibited tyrosinase inhibitory activities (IC50 values of 44.86 µM and 69.85 µM respectively). Docking results confirm that the active inhibitors strongly interact with tyrosinase residues.


Asunto(s)
Azadirachta/química , Diterpenos/química , Limoninas/química , Melaninas/metabolismo , Animales , Azadirachta/metabolismo , Sitios de Unión , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diterpenos/metabolismo , Diterpenos/farmacología , Limoninas/metabolismo , Limoninas/farmacología , Ratones , Conformación Molecular , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Corteza de la Planta/química , Corteza de la Planta/metabolismo , Raíces de Plantas/química , Raíces de Plantas/metabolismo
7.
Bioorg Chem ; 100: 103889, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32388432

RESUMEN

The chemical constituents of the roots, seeds, and bark of Azadirachta indica var. siamensis were investigated, leading to the isolation of six tricyclic diterpenoids and five limonoids, including two new compounds (2, 5). The structures were elucidated based on NMR spectroscopic techniques, mass spectrometry and single-crystal X-ray diffraction as well as comparison with the literature. Moreover, the cytotoxicity activities of the isolates were evaluated. The results indicated that the compounds 1-3, 5-9 exhibited cytotoxicities against one or more cancer cell lines tested, with IC50 values in the range of 1.7-88.1 µM. The mechanism of action studies indicated that the most active compound, compound 5, could induce the apoptosis of AZ521 cells. Furthermore, the Western blot analysis showed that compound 5 could reduce the expression levels of procaspases-3, -8, -9 and promote the expression of Bid and AIF.


Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Azadirachta/química , Diterpenos/química , Diterpenos/farmacología , Limoninas/química , Limoninas/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Diterpenos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Limoninas/aislamiento & purificación , Modelos Moleculares , Neoplasias/tratamiento farmacológico
8.
Pharmacol Biochem Behav ; 242: 173809, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936482

RESUMEN

TPN672MA, an innovative antipsychotic drug candidate currently in clinical trials, acts as a dopamine D2/D3 receptor partial agonist, serotonin 5-HT1A receptor agonist, and serotonin 5-HT2A receptor antagonist. Preclinical investigations have demonstrated its potential in treating the core symptoms of schizophrenia. The present study highlights TPN672MA's significant antidepressant-like effects in classical behavioral models, such as the chronic social defeat stress paradigm. The pronounced 5-HT1A receptor agonism and D2/D3 receptor partial agonism of TPN672MA likely contribute to its therapeutic effects in depression. Additionally, TPN672MA's antidepressant-like efficacy may be linked to its ability to enhance the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD95) in the hippocampus. Furthermore, TPN672MA displayed a more rapid onset of antidepressant-like action. In conclusion, TPN672MA represents a promising new drug candidate for the treatment of symptoms of schizophrenia and depression.

9.
Sci Rep ; 14(1): 5761, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459079

RESUMEN

To further investigate the weakening effect of pore water pressure on intact rock mechanics properties and characteristics of fracture surface after failure, direct shear tests of sandstone were conducted under different pore pressure. A 3D scanner was employed to digitize the morphology of the post-shear fracture surface. The variogram function was applied to quantify the anisotropic characteristics of post-shear fracture surface. The relationship between deformation during shear failure of intact rock and quantitative parameters of fracture surface after shear failure was initially established. It can be found that amplitudes of the sinusoidal surface determine the maximum value of variogram, and period affect lag distance that reach the maximum value of variogram. Test results revealed that the increase of pore pressure has obvious weakening effect on shear strength and deformation of rock. Moreover, the increase of pore pressure makes the shear fracture surface flatter. It can be obtained that both Sillmax and Rangemax are positively related to shear strain, but negatively related to normal strain.

10.
Eur J Med Chem ; 275: 116564, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38875810

RESUMEN

Depression is a common psychiatric disorder with an estimated global prevalence of 4.4 %. Here, we designed a series of new multimodal monoaminergic arylpiperazine derivatives using a pharmacophore hybrid approach and synthesized them for the treatment of depression. Molecular docking was employed to elucidate the differences in activity and selectivity of the corresponding compounds on SERT, NET, and DAT. In vitro experiments demonstrated that compound A3 has a relatively balanced multi-target activity profile with SERT reuptake inhibition (IC50 = 12 nM), NET reuptake inhibition (IC50 = 78 nM), DAT reuptake inhibition (IC50 = 135 nM), and 5-HT1AR agonism (EC50 = 34 nM). Pharmacokinetic experiments revealed that A3 exhibited excellent bioavailability and low clearance in mice. Subsequent behavioral experiments further confirmed its significant antidepressant effects. These results further highlight the rationality of our design strategy.

11.
Neurosci Lett ; 826: 137723, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38467272

RESUMEN

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD's interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 µM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD's anxiolytic-like effects. Additionally, CBD's effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD's anxiolytic-like and antipsychotic-like effects.


Asunto(s)
Ansiolíticos , Antipsicóticos , Cannabidiol , Cricetinae , Ratones , Ratas , Humanos , Animales , Antipsicóticos/farmacología , Ansiolíticos/farmacología , Cannabidiol/farmacología , Serotonina , Cricetulus , Cromatografía Liquida , Espectrometría de Masas en Tándem , Ácido gamma-Aminobutírico
12.
JAMA Surg ; 159(5): 519-528, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38416471

RESUMEN

Importance: The current TNM staging system may not provide adequate information for prognostic purposes and to assess the potential benefits of chemotherapy for patients with stage III colon cancer. Objective: To develop and validate a pathomics signature to estimate prognosis and benefit from chemotherapy using hematoxylin-eosin (H-E)-stained slides. Design, Setting, and Participants: This retrospective prognostic study used data from consecutive patients with histologically confirmed stage III colon cancer at 2 medical centers between January 2012 and December 2015. A total of 114 pathomics features were extracted from digital H-E-stained images from Nanfang Hospital of Southern Medical University, Guangzhou, China, and a pathomics signature was constructed using a least absolute shrinkage and selection operator Cox regression model in the training cohort. The associations of the pathomics signature with disease-free survival (DFS) and overall survival (OS) were evaluated. Patients at the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, formed the validation cohort. Data analysis was conducted from September 2022 to March 2023. Main Outcomes and Measures: The prognostic accuracy of the pathomics signature as well as its association with chemotherapy response were evaluated. Results: This study included 785 patients (mean [SD] age, 62.7 [11.1] years; 437 [55.7%] male). A pathomics signature was constructed based on 4 features. Multivariable analysis revealed that the pathomics signature was an independent factor associated with DFS (hazard ratio [HR], 2.46 [95% CI, 2.89-4.13]; P < .001) and OS (HR, 2.78 [95% CI, 2.34-3.31]; P < .001) in the training cohort. Incorporating the pathomics signature into pathomics nomograms resulted in better performance for the estimation of prognosis than the traditional model in a concordance index comparison in the training cohort (DFS: HR, 0.88 [95% CI, 0.86-0.89] vs HR, 0.73 [95% CI, 0.71-0.75]; P < .001; OS: HR, 0.85 [95% CI, 0.84-0.86] vs HR, 0.74 [95% CI, 0.72-0.76]; P < .001) and validation cohort (DFS: HR, 0.83 [95% CI, 0.82-0.85] vs HR, 0.70 [95% CI, 0.67-0.72]; P < .001; OS: HR, 0.80 [95% CI, 0.78-0.82] vs HR, 0.69 [0.67-0.72]; P < .001). Further analysis revealed that patients with a low pathomics signature were more likely to benefit from chemotherapy (eg, combined cohort: DFS: HR, 0.44 [95% CI, 0.28-0.69]; P = .001; OS: HR, 0.43 [95% CI, 0.29-0.64]; P < .001). Conclusions and Relevance: These findings suggest that a pathomics signature could help identify patients most likely to benefit from chemotherapy in stage III colon cancer.


Asunto(s)
Neoplasias del Colon , Estadificación de Neoplasias , Humanos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias del Colon/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Pronóstico , Anciano , Supervivencia sin Enfermedad , Quimioterapia Adyuvante
13.
Medicine (Baltimore) ; 102(27): e34228, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37417594

RESUMEN

BACKGROUND: Immunotherapy is a promising method for the treatment of endometrial cancer (EC). We aimed to conduct a comprehensive bibliometric study of the top 100 most-cited publications on immunotherapy for EC and provide a reference for future research. METHODS: Global publications on immunotherapy for EC published from 1985 to the present in the Web of Science core database were retrieved. We focused on the study of the top 100 most-cited articles by extracting information such as year, country, journal, author, institution, literature, and keywords. Microsoft Excel, VOSviewer, and R were used to perform descriptive statistics and visual analyses. RESULTS: The top 100 most-cited articles were published between 2002 and 2022, including 70 original papers and 30 reviews. The total frequency of citations per article ranges from 15 to 287. Developed countries dominated these publications, with the United States contributing the most (50 articles). According to Bradford Law, 6 journals, including Gynecologic Oncology and the Journal of Clinical Oncology, are highly recommended. Santin A. D. from Yale University and Makker.V. from Memorial Sloan Kettering Cancer Center have made positive contributions. Among the top ten most-cited articles, 7 focused on clinical trials exploring the efficacy of immunotherapy drugs, of which 4 were lenvatinib combined with pembrolizumab for the treatment of advanced EC. The immune-microenvironment, immune antitumor mechanisms, immunomodulatory drugs, especially anti-pd-1/pd-l1 checkpoint inhibitors, and their clinical trials are the focus of current research. CONCLUSION: The attention of researchers from different countries to EC immunotherapy, especially immunosuppressants, has brought a breakthrough in this field. A large number of clinical trials have evaluated the efficacy and safety of immune agents, and immune combination therapy (especially targeted therapy) shows positive therapeutic promise. Immunodrug sensitivity and adverse events remain urgent issues. The key to promoting the development of EC immunotherapy is to select the best patients according to the molecular classification and immunophenotype such as tumor mutation load, MMR status, pd-l1 expression, tumor infiltrating immune cells to truly achieve accurate and personalized treatment. More new and influential EC immunotherapies, such as adoptive cell immunotherapy, still need to be explored in future clinical practice.


Asunto(s)
Antígeno B7-H1 , Neoplasias Endometriales , Humanos , Femenino , Inmunoterapia , Neoplasias Endometriales/terapia , Inmunoterapia Adoptiva , Bibliometría , Microambiente Tumoral
14.
Drug Discov Ther ; 17(4): 248-256, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37599085

RESUMEN

Ferroptosis is a form of regulated cell death (RCD) triggered by iron-dependent lipid peroxidation and is closely associated with the occurrence and progression of hepatocellular carcinoma (HCC). The lncRNA SNHG1 (small nucleolar RNA host gene 1) has been shown to play an oncogenic role in HCC, but its function in RCD other than autophagy and apoptosis is still unknown. Here, we investigated the correlation between SNHG1 and 156 typical markers of five RCD types based on RNA sequencing data from The Cancer Genome Atlas database and showed the negative regulators of ferroptosis FANCD2 (Fanconi anemia complementation group D2) and G6PD (glucose-6-phosphate dehydrogenase) to be the most highly and fifth most highly correlating factors with SNHG1, respectively. A competitive endogenous RNA network of SNHG1 - miR-199a-5p/3p - FANCD2/G6PD was constructed bioinformatically. In vitro experiments showed that overexpression of the miR-199a precursor led to a decrease in expression of SNHG1, FANCD2, and G6PD, whereas knockdown of SNHG1 decreased expression of FANCD2 and G6PD but increased levels of miR-199a-5p and miR-199a-3p in HCC cells (Huh7 and HepG2). In addition, knockdown of SNHG1 increased erastin-mediated ferroptosis, iron accumulation, and lipid peroxidation. These results suggest that SNHG1 upregulates FANCD2 and G6PD by sponging miR-199a, thereby inhibiting ferroptosis in HCC. Moreover, a signature based on expression of SNHG1, FANCD2, and G6PD was identified as being associated with overall survival and the immunological microenvironment in HCC. Collectively, this study identified the SNHG1-miR-199a-FANCD2/G6PD axis in HCC, which is a potential marker for the prognosis and therapy of this tumor.


Asunto(s)
Carcinoma Hepatocelular , Anemia de Fanconi , Ferroptosis , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/genética , Ferroptosis/genética , ARN Largo no Codificante/genética , Glucosafosfato Deshidrogenasa/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Microambiente Tumoral , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi
15.
Biosensors (Basel) ; 13(5)2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37232925

RESUMEN

A capture systematic evolution of ligands by exponential enrichment (Capture-SELEX) was described to discover novel aptamers specific for 5-hydroxymethylfurfural (5-HMF), and a biosensor based on molecular beacon was constructed to detect 5-HMF. The ssDNA library was immobilized to streptavidin (SA) resin to select the specific aptamer. The selection progress was monitored using real-time quantitative PCR (Q-PCR), and the enriched library was sequenced by high-throughput sequencing (HTS). Candidate and mutant aptamers were selected and identified by Isothermal Titration Calorimetry (ITC). The FAM-aptamer and BHQ1-cDNA were designed as the quenching biosensor to detect 5-HMF in milk matrix. After the 18th round selection, the Ct value decreased from 9.09 to 8.79, indicating that the library was enriched. The HTS results indicated that the total sequence numbers for 9th, 13th, 16th, and 18th were 417054, 407987, 307666, and 259867, but the number of sequences for the top 300 sequences was gradually increased from 9th to 18th, and the ClustalX2 analysis showed that there were four families with high homology rate. ITC results indicated that the Kd values of H1 and its mutants H1-8, H1-12, H1-14, and H1-21 were 2.5 µM, 1.8 µM, 1.2 µM, 6.5 µM, and 4.7 µM. The linear range of the quenching biosensor was from 0 µM to 75 µM, and it had a similar linear range in the 0.1% milk matrix. This is the first report to select a novel aptamer specific for 5-HMF and develop quenching biosensor for the rapid detection of 5-HMF in milk matrix.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Humanos , Aptámeros de Nucleótidos/química , ADN de Cadena Simple , Furaldehído
16.
FEBS J ; 290(14): 3614-3628, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36866961

RESUMEN

Metabolic reprogramming is a hallmark of cancer. Several studies have shown that inactivation of Krebs cycle enzymes, such as citrate synthase (CS) and fumarate hydratase (FH), facilitates aerobic glycolysis and cancer progression. MAEL has been shown to play an oncogenic role in bladder, liver, colon, and gastric cancers, but its role in breast cancer and metabolism is still unknown. Here, we demonstrated that MAEL promoted malignant behaviours and aerobic glycolysis in breast cancer cells. Mechanistically, MAEL interacted with CS/FH and HSAP8 via its MAEL domain and HMG domain, respectively, and then enhanced the binding affinity of CS/FH with HSPA8, facilitating the transport of CS/FH to the lysosome for degradation. MAEL-induced degradation of CS and FH could be suppressed by the lysosome inhibitors leupeptin and NH4 Cl, but not by the macroautophagy inhibitor 3-MA or the proteasome inhibitor MG132. These results suggested that MAEL promoted the degradation of CS and FH via chaperone-mediated autophagy (CMA). Further studies showed that the expression of MAEL was significantly and negatively correlated with CS and FH in breast cancer. Moreover, overexpression of CS or/and FH could reverse the oncogenic effects of MAEL. Taken together, MAEL promotes a metabolic shift from oxidative phosphorylation to glycolysis by inducing CMA-dependent degradation of CS and FH, thereby promoting breast cancer progression. These findings have elucidated a novel molecular mechanism of MAEL in cancer.


Asunto(s)
Neoplasias de la Mama , Autofagia Mediada por Chaperones , Humanos , Femenino , Neoplasias de la Mama/genética , Fumarato Hidratasa/genética , Fumarato Hidratasa/metabolismo , Citrato (si)-Sintasa/metabolismo , Ciclo del Ácido Cítrico , Autofagia
17.
Anal Chim Acta ; 1271: 341460, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37328245

RESUMEN

Surface plasmon coupled emission (SPCE), a novel surface-enhanced fluorescence technique, can generate directional and amplified radiation by the intense interaction between fluorophores and surface plasmons (SPs) of metallic nanofilms. For plasmon-based optical systems, the strong interaction between localized and propagating SPs and "hot spot" structures show great potential to significantly improve the electromagnetic (EM) field and modulate optical properties. Au nanobipyramids (NBPs) with two sharp apexes to enhance and restrict the EM field were introduced through electrostatic adsorption to achieve a mediated fluorescence system, and the emission signal enhancement was realized by factors over 60 compared with the normal SPCE. It has been demonstrated that the intense EM field produced by the NBPs assembly is what triggered the unique enhancement of SPCE by Au NBPs, which effectively overcomes the inherent signal quenching of SPCE for ultrathin sample detection. This remarkable enhanced strategy offers the chance to improve the detection sensitivity for plasmon-based biosensing and detection systems, and expand the range of applications for SPCE in bioimaging with more comprehensive and detailed information acquisition. The enhancement efficiency for various emission wavelengths was investigated in light of the wavelength resolution of SPCE, and it was discovered that enhanced emission for multi-wavelength could be successfully detected through the different emission angles due to the angular displacement caused by wavelength change. Benefit from this, the Au NBP modulated SPCE system was employed for multi-wavelength simultaneous enhancement detection under a single collection angle, which could broaden the application of SPCE in simultaneous sensing and imaging for multi-analytes, and expected to be used for high throughput detection of multi-component analysis.


Asunto(s)
Colorantes Fluorescentes , Resonancia por Plasmón de Superficie , Resonancia por Plasmón de Superficie/métodos , Colorantes Fluorescentes/química
18.
Surg Laparosc Endosc Percutan Tech ; 33(4): 382-390, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37311044

RESUMEN

BACKGROUND: The accurate determination of lymph node status in patients with rectal cancer requires harvesting a certain number of lymph nodes. This study investigated whether using carbon nanoparticles (CNs) could improve the efficiency of harvesting lymph nodes in rectal cancer patients. MATERIALS AND METHODS: Data from patients with rectal cancer treated with radical resection were collected from Nanfang Hospital between January 2014 and June 2021. Patients in the CN group received a CN suspension 1 day before surgery, which was endoscopically injected around the tumor. A 1:1 case-matched study was performed using the propensity score. The efficiency of harvesting lymph nodes was investigated by comparing the number of total nodes, total time, and percentage of nodes <5 mm in size between the CN and non-CN groups. RESULTS: A total of 768 patients were included, with 246 patients who underwent CN injection and 522 patients who did not. After matching, 246 pairs of patients were analyzed. After matching, the number of total nodes of each sample was significantly higher in the CN group than in the non-CN group ( P <0.001). The total time for node detection ( P <0.001) was significantly shorter in the CN group. The percentage of nodes <5 mm in size was increased significantly in the CN group ( P <0.001). Among patients with clinical staging I/II, the difference in positive LNs was significant (21.79% vs. 11.95%, P =0.029). CONCLUSIONS: The application of CNs improved the efficiency of harvesting lymph nodes during rectal cancer surgery.


Asunto(s)
Nanopartículas , Neoplasias del Recto , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Carbono
19.
Bioeng Transl Med ; 8(3): e10526, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37206212

RESUMEN

The current tumor-node-metastasis staging system does not provide sufficient prognostic prediction or adjuvant chemotherapy benefit information for stage II-III colon cancer (CC) patients. Collagen in the tumor microenvironment affects the biological behaviors and chemotherapy response of cancer cells. Hence, in this study, we proposed a collagen deep learning (collagenDL) classifier based on the 50-layer residual network model for predicting disease-free survival (DFS) and overall survival (OS). The collagenDL classifier was significantly associated with DFS and OS (P < 0.001). The collagenDL nomogram, integrating the collagenDL classifier and three clinicopathologic predictors, improved the prediction performance, which showed satisfactory discrimination and calibration. These results were independently validated in the internal and external validation cohorts. In addition, high-risk stage II and III CC patients with high-collagenDL classifier, rather than low-collagenDL classifier, exhibited a favorable response to adjuvant chemotherapy. In conclusion, the collagenDL classifier could predict prognosis and adjuvant chemotherapy benefits in stage II-III CC patients.

20.
Waste Manag ; 172: 326-334, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37948828

RESUMEN

The occurrence of microplastics (MPs) in aquatic ecosystems has become an increasingly serious threat to public health. Marine sediments are considered the final recipients of all microplastic pollution from inland rivers, however, whether and how the MPs differ in these two ecosystems remains poorly known due to the divergent MPs detection methods employed in previous studies. Here, we investigated the abundance, size, and types of MPs in sediment samples from the Yellow River and Yellow Sea using laser direct infrared (LDIR), and assessed their ecological risks. The abundance of MPs in the Yellow Sea is 2.9 times higher than that in the Yellow River, with an average abundance of 54813.2 ± 19355.9 and 18780.2 ± 9951.8 particles·kg-1 (dry sediment), respectively. Notably, the predominant polymer types in both sediment environments were silicone, fluororubber, and polypropylene (PP). MPs with sizes < 100 µm accounted for > 90 % of the total MPs number. Risk assessment demonstrated all the sediment environments exhibited high ecological risks. The dominance of small MPs highlighted the importance of using a method with high resolution to delineate the truthful status of MP pollution.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Plásticos , Ecosistema , Ríos , Contaminantes Químicos del Agua/análisis , Sedimentos Geológicos , Monitoreo del Ambiente/métodos , Medición de Riesgo
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