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Long noncoding RNAs (lncRNAs) are crucial regulators of tumor-initiating cells (TICs) and hold particular importance in triple negative breast cancer (TNBC). Yet, the precise mechanisms by which TIC-associated lncRNAs influence TNBC remain unclear. Our research utilized The Cancer Genome Atlas Breast Cancer (BC) data set to identify prognostic lncRNAs. We then conducted extensive assays to explore their impact on the tumor-initiating phenotype of TNBC cells and the underlying mechanisms. Notably, we found that low expression of lncRNA SEMA3B-AS1 correlated with unfavorable survival in BC patients. SEMA3B-AS1 was also downregulated in TNBC and linked to advanced tumor stage. Functional experiments confirmed its role as a TIC-suppressing lncRNA, curtailing mammosphere formation, ALDH + TIC cell proportion, and impairing clonogenicity, migration, and invasion. Mechanistic insights unveiled SEMA3B-AS1's nuclear localization and interaction with MLL4 (mixed-lineage leukemia 4), triggering H3K4 methylation-associated transcript activation and thus elevating the expression of SEMA3B, a recognized tumor suppressor gene. Our findings emphasize SEMA3B-AS1's significance as a TNBC-suppressing lncRNA that modulates TIC behavior. This study advances our comprehension of lncRNA's role in TNBC progression, advocating for their potential as therapeutic targets in this aggressive BC subtype.
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MicroARNs , ARN Largo no Codificante , Semaforinas , Neoplasias de la Mama Triple Negativas , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de la Mama Triple Negativas/patología , MicroARNs/genética , N-Metiltransferasa de Histona-Lisina/genética , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Línea Celular Tumoral , Glicoproteínas de Membrana/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Semaforinas/uso terapéuticoRESUMEN
BACKGROUND: In lactating women, iodine metabolism is regulated and maintained by the kidneys and mammary glands. Limited research exists on how iodine absorbed by lactating women is distributed between the kidneys and breasts. OBJECTIVES: This study aimed to accurately evaluate the total iodine intake (TII), urinary iodine excretion (UIE), and breast milk iodine excretion (BMIE) in lactating women and explore the relationship between TII and total iodine excretion (TIE). METHODS: A 7-d iodine metabolism study was conducted on 41 lactating women with a mean age of 30 y in Yuncheng and Gaoqing, China, from December 2021 to August 2023. TII and TIE were calculated by measuring the iodine content in food, water, 24-h urine, feces, and breast milk. The urinary iodine excretion rate (UIER), breast milk iodine excretion rate (BMIER), and partitioning of iodine excretion between urine and breast milk were determined. RESULTS: Iodine metabolism studies were performed for 285 d. The median TII and TIE values were 255 and 263 µg/d, respectively. With an increase in TII, UIER, and BMIER, the UIE and BMIE to TII ratio exhibited a downward trend. The median UIER, BMIER, and proportion of iodine excreted in urine and breast milk were 51.5%, 38.5%, 52%, and 37%, respectively. When the TII was <120 µg/d, the BMIER decreased with the increase of the TII (ß: -0.90; 95% confidence interval: -1.08, -0.72). CONCLUSIONS: When maternal iodine intake is low, the proportion in breast milk increases, ensuring sufficient iodine nutrition for infants. In addition, the UIE of lactating women with adequate iodine concentrations is higher than their BMIE. This study was registered at clinicaltrials.gov as NCT04492657.
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Yodo , Lactancia , Leche Humana , Adulto , Femenino , Humanos , China , Yodo/orina , Yodo/metabolismo , Lactancia/metabolismo , Leche Humana/química , Leche Humana/metabolismo , Estudios de CohortesRESUMEN
Breast cancer is one of the most common malignant diseases in women. Triple-negative breast cancer (TNBC) shows higher aggressiveness and recurrence rates than other subtypes, and there are no effective targets or tailored treatments for TNBC patients. Thus, finding effective prognostic markers for TNBC could help clinicians in their ability to care for their patients. We used tissue microarrays (TMAs) to detect microRNA-493 (miR-493) expression in breast cancer samples. A miRCURY LNA detection probe specific for miR-493 was used in in situ hybridization assays. Staining results were reviewed by two independent pathologists and classified as high or low expression of miR-493. Kaplan-Meier survival plots and multivariate Cox analysis were carried out to clarify the relationship between miR-493 and survival. In the Kaplan-Meier analysis, patients with high miR-493 expression had better disease-free survival than patients with low miR-493 expression. After adjusting for common clinicopathological factors in breast cancer, the expression level of miR-493 was still a significant prognostic factor in breast cancer. Further subtype analysis revealed that miR-493 expression levels were only significantly prognostic in TNBC patients. These results were validated in the Molecular Taxonomy of Breast Cancer International Consortium database for overall survival. We proved the prognostic role of miR-493 in TNBC by using one of the largest breast cancer TMAs available and validated it in a large public RNA sequencing database.
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MicroARNs/biosíntesis , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Biomarcadores de Tumor , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Mama Triple Negativas/mortalidadRESUMEN
In this study, we designed a plain strategy for fabrication of the novel composite ZnO/CuCo2O4 and applied it as catalyst for peroxymonosulfate (PMS) activation to decompose enrofloxacin (ENR) under simulated sunlight. Compared to ZnO and CuCo2O4 alone, the ZnO/CuCo2O4 composite could significantly activate PMS under simulated sunlight, resulting in the generation of more active radicals for ENR degradation. Thus, 89.2 % of ENR could be decomposed over 10 min at natural pH. Furthermore, the influences of the experimental factors, including the catalyst dose, PMS concentration, and initial pH, on ENR degradation were evaluated. Subsequent active radical trapping experiments indicated that sulfate, superoxide, and hydroxyl radicals together with holes (h+) were involved in the degradation of ENR. Notably, the ZnO/CuCo2O4 composite exhibited good stability. Only 10 % decrease in ENR degradation efficiency was observed after four runs. Finally, several reasonable ENR degradation pathways were proposed, and the mechanism of PMS activation was elucidated. This study provides a novel strategy by integrating state-of-the-art material science and advanced oxidation technology for wastewater treatment and environmental remediation.
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Óxido de Zinc , Enrofloxacina , Peróxidos , SuperóxidosRESUMEN
Persistent oxidative stress and recurring waves of inflammation with excessive reactive oxygen species (ROS) and free radical accumulation could be generated by radiation. Exposure to radiation in combination with physical injuries such as wound trauma would produce a more harmful set of medical complications, which was known as radiation combined with skin wounds (RCSWs). However, little attention has been given to RCSW research despite the unsatisfactory therapeutic outcomes. In this study, a dual-nanoagent-loaded multifunctional hydrogel was fabricated to ameliorate the pathological microenvironment associated with RCSWs. The injectable, adhesive, and self-healing hydrogel was prepared by crosslinking carbohydrazide-modified gelatin (Gel-CDH) and oxidized hyaluronic acid (OHA) through the Schiff-base reaction under mild condition. Polydopamine nanoparticles (PDA-NPs) and mesenchymal stem cell-secreted small extracellular vesicles (MSC-sEV) were loaded to relieve radiation-produced tissue inflammation and oxidation impairment and enhance cell vitality and angiogenesis individually or jointly. The proposed PDA-NPs@MSC-sEV hydrogel enhanced cell vitality, as shown by cell proliferation, migration, colony formation, and cell cycle and apoptosis assays in vitro, and promoted reepithelization by attenuating microenvironment pathology in vivo. Notably, a gene set enrichment analysis of proteomic data revealed significant enrichment with adipogenic and hypoxic pathways, which play prominent roles in wound repair. Specifically, target genes were predicted based on differential transcription factor expression. The results suggested that MSC-sEV- and PDA-NP-loaded multifunctional hydrogels may be promising nanotherapies for RCSWs. STATEMENT OF SIGNIFICANCE: The small extracellular vesicle (sEV) has distinct advantages compared with MSCs, and polydopamine nanoparticles (PDA-NPs), known as the biological materials with good cell affinity and histocompatibility which have been reported to scavenge ROS free radicals. In this study, an adhesive, injectable, self-healing, antibacterial, ROS scavenging and amelioration of the radiation related microenvironment hydrogel encapsulating nanoscale particles of MSC-sEV and PDA-NPs (PDA-NPs@MSC-sEV hydrogel) was synthesized for promoting radiation combined with skin wounds (RCSWs). GSEA analysis profiled by proteomics data revealed significant enrichments in the regulations of adipogenic and hypoxic pathways with this multi-functional hydrogel. This is the first report of combining this two promising nanoscale agents for the special skin wounds associated with radiation.
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Hidrogeles , Proteómica , Humanos , Cicatrización de Heridas , Antibacterianos , InflamaciónRESUMEN
Purpose: The role of 5-methylcytosine-related long non-coding RNAs (m5C-lncRNAs) in breast cancer (BC) remains unclear. Here, we aimed to investigate the prognostic value, gene expression characteristics, and correlation between m5C-lncRNA risk model and tumor immune cell infiltration in BC. Methods: The expression matrix of m5C-lncRNAs in BC was obtained from The Cancer Genome Atlas database, and the lncRNAs were analyzed using differential expression analysis as well as univariate and multivariate Cox regression analysis to eventually obtain BC-specific m5C-lncRNAs. A risk model was developed based on three lncRNAs using multivariate Cox regression and the prognostic value, accuracy, as well as reliability were verified. Gene set enrichment analysis (GSEA) was used to analyze the Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment of the risk model. CIBERSORT algorithm and correlation analysis were used to explore the characteristics of the BC tumor-infiltrating immune cells. Finally, reverse transcription-quantitative polymerase chain reaction was performed to detect the expression level of three lncRNA in clinical samples. Results: A total of 334 differential m5C-lncRNAs were identified, and three BC-specific m5C-lncRNAs were selected, namely AP005131.2, AL121832.2, and LINC01152. Based on these three lncRNAs, a highly reliable and specific risk model was constructed, which was proven to be closely related to the prognosis of patients with BC. Therefore, a nomogram based on the risk score was built to assist clinical decisions. GSEA revealed that the risk model was significantly enriched in metabolism-related pathways and was associated with tumor immune cell infiltration based on the analysis with the CIBERSORT algorithm. Conclusion: The efficient risk model based on m5C-lncRNAs associated with cancer metabolism and tumor immune cell infiltration could predict the survival prognosis of patients, and AP005131.2, AL121832.2, and LINC01152 could be novel biomarkers and therapeutic targets for BC.
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[This corrects the article on p. 3302 in vol. 10, PMID: 33163271.].
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A FLUENT software able to predict and assess the electrooxidation of ammonia from the simulation of ammonia concentration and flow field distribution was developed in this study. The flow field-based models of ammonia removal were simulated and modified through the experimental results. The parameter of reaction constant k is corrected to 0.00195, and the modified model fitted well with experimental values, with the error less than 4%. The electrode depth of 4 cm was assessed to be optimal for ammonia removal based on the comparison of the simulation results on ammonia concentration and flow field distribution. The prediction result applied in the industrial wastewater treatment indicated that complete could be achieved at 0.27 Ah/L, and about 50% of total nitrogen was removed at 0.8 Ah/L. About 7% of chloride ions were converted into inorganic by-products, indicating low biological toxicity and risk on environment. The energy consumption increased with the promotion of removal efficiency of total nitrogen, requiring 5.4 kWh/m3 to remove 50% total nitrogen at 0.8 Ah/L. The results show the practicability and feasibility of this FLUENT software tool on the simulation and prediction of electrooxidation process, which can provide the simulation parameter settings for the subsequent application. PRACTITIONER POINTS: A FLUENT software based on the simulation of ammonia concentration and flow field distribution was able to predict and assess ammonia electrooxidation. A modified model is provided with a rate constant k of 0.00195 and the distinction of 4% with experimental results. The optimal electrode depth was predicted to be 4 cm via the obtained model. Complete ammonia and about 50% of total nitrogen could be at 0.27 Ah/L and 0.8 Ah/L, receptively. About 7% of chloride ions were converted into inorganic by-products in industrial wastewater with high chloride.
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Amoníaco , Aguas Residuales , Electrodos , Nitrógeno , Eliminación de Residuos LíquidosRESUMEN
Reducing the material size could be an effective approach to enhance the electrochemical performance of porous carbons for supercapacitors. In this work, ultra-fine porous carbon nanofibers are prepared by electrospinning using lignin/ polyvinylpyrrolidone as carbon precursor and zinc nitrate hexahydrate (ZNH) as an additive, followed by pre-oxidation, carbonization, and pickling processes. Assisted by the ZnO template, the pyrolytic product of ZNH, abundant micropores are yielded, leading to the formation of microporous carbon nanofibers with specific surface area (SSA) up to 1363 m2 g-1. The average diameter of the lignin-based ultra-fine porous carbon nanofibers (LUPCFs) is effectively controlled from 209 to 83 nm through adjusting the ZNH content. With good flexibility and self-standing nature, the LUPCFs could be directly cut into electrodes for use in supercapacitors. High accessible surface, enriched surface N/O groups, and reduced fiber diameters endow the LUPCFs-based electrodes with an excellent specific capacitance of 289 F g-1. The reduction of fiber diameters remarkably improves the rate performance of the LUPCFs and leads to a low relaxation time constant of 0.37 s. The high specific capacitance of 162 F g-1 is maintained when the current density is increased from 0.1 to 20 A g-1. Besides, the fabricated LUPCFs show exceptional cycling stability in symmetrical supercapacitors, manifesting a promising application prospect in the next generation of supercapacitors.
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Multidrug chemoresistance is a major clinical obstacle in breast cancer treatment. We aimed to elucidate the sensitivity to therapeutics in gemcitabine-resistant breast cancer models. Pooled library screening combined with RNA-seq was conducted to explore the potential targets involved in gemcitabine resistance in breast cancer cells. Cytotoxicity and tumor xenograft assays were used to evaluate the effect of calcium-activated channel subfamily N member 4 (KCNN4) inhibitors on the cellular sensitivity of breast cancer cells to chemotherapeutic drugs both in vitro and in vivo. We found that KCNN4 is an important determinant for the cytotoxicity of gemcitabine. Elevated KCNN4 expression enhanced resistance to chemotherapeutic antimetabolites and promoted cell proliferation. Conversely, silencing KCNN4 or chemical inhibition of KCNN4 by the specific inhibitor TRAM-34 inhibited the chemoresistance and cell proliferation. Mechanistically, KCNN4 upregulated BCL2-related protein A1 (BCL2A1) to suppress apoptosis by activating RAS-MAPK and PI3K-AKT signaling. Moreover, high expression levels of KCNN4 and BCL2A1 were associated with shortened disease-free survival in the cohort studies. Collectively, our findings showed that KCNN4 is a key modulator of progression and drug resistance in breast cancer, indicating that targeting KCNN4 may serve as a promising therapeutic strategy to overcome multidrug chemoresistance in this disease.
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In this study, bimetal layered double hydroxides (CoxCuy-LDHs) containing a carbonate interlayer were synthesized using coprecipitation with a variety of Co/Cu mole ratios. Meanwhile, the corresponding layered double oxides (CoxCuy-LDOs) were prepared as controls. In this study, Electrical energy per order was performed to evaluate economic analysis. Correspondingly, we found that CoxCuy-LDHs possessed a significantly better PMS activation capability than the corresponding metal oxide composite (Co3O4/CuO). Compared with other CoxCuy-LDHs, Co2Cu1 LDH possessed the best PMS activation capability for LOM degradation and the lowest electrical energy per order (EE/O) value during the reaction. Additionally, Co2Cu1 LDH presented an excellent stability and worked over a wide pH range. The hydroxide states of Co(III), Co(II), Cu(I) and Cu(II) were all able to activate PMS, indicating that there were many active sites on the surface of Co2Cu1 LDH. The involvement of radicals in this reaction system was determined via scavenger experiments and electron paramagnetic resonance (EPR). Meanwhile, it's worth noting that a mathematical model was developed to quantify the involvement of SO4- and OH. Subsequently, we determined PMS activation mechanism and LOM decomposition pathway for the PMS/Co2Cu1 LDH system.
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Fluoroquinolonas , Peróxidos , ÓxidosRESUMEN
One of the topics gaining lots of recent attention is the antimony (Sb) pollution. We have designed a dual-functional electroactive filter consisting of one-dimensional (1-D) titanate nanowires and carbon nanotubes for simultaneous oxidation and sorption of Sb(III). Applying an external limited DC voltage assist the in-situ conversion of highly toxic Sb(III) to less toxic Sb(V). The Sb(III) removal kinetics and efficiency were enhanced with flow rate and applied voltage (e.g., the Sb(III) removal efficiency increased from 87.5% at 0â¯V to 96.2% at 2â¯V). This enhancement in kinetics and efficiency are originated from the flow-through design, more exposed sorption sites, electrochemical reactivity, and limited pore size on the filter. The titanate-CNT hybrid filters perform effectively across a wide pH range of 3-11. Only negligible inhibition was observed in the presence of nitrate, chloride, and carbonate at varying concentrations. Our analyses using STEM, XPS, or AFS demonstrate that Sb were mainly adsorbed by Ti. DFT calculations suggest that the Sb(III) oxidation kinetics can be accelerated by the applied electric field. Exhausted titanate-CNT filters can be effectively regenerated by using NaOH solution. Moreover, the Sb(III)-spiked tap water generated â¼2400 bed volumes with a >90% removal efficiency. This study provides new insights for rational design of continuous-flow filters for the decontamination of Sb and other similar heavy metal ions.
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Antimonio/análisis , Técnicas Electroquímicas/métodos , Filtración/instrumentación , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Adsorción , Cinética , Nanotubos de Carbono/química , Nanocables/química , Oxidación-Reducción , Polvos , Propiedades de Superficie , Titanio/químicaRESUMEN
BACKGROUND: Spinal neurosyphilis manifesting as a solitary syphilitic gumma is exceedingly rare. There are non-specific imaging findings and challenges in the diagnosis of spinal syphilitic gumma, which could be easily misdiagnosed as tumor lesions and require surgical resection or biopsy. CLINICAL PRESENTATION: We report the case of a 45-year-old female patient who was diagnosed with Spinal syphilitic gumma. Our case is the first reported case of spinal cord syphilitic gumma with intradural-extramedullary and intramedullary involvement. CONCLUSION: Spinal syphilitic gumma exhibits diverse clinical manifestations, lacks specific imaging features, accompanied by the patient's history deliberately concealed. Since clinicians do not have sufficient knowledge about such rare cases, misdiagnosis and missed diagnosis will be likely. When there is clinical suspicion for spinal syphilitic gumma, clinicians should pay close attention to relevant medical history, carry out a comprehensive physical examination and specific serological tests and cerebrospinal fluid (CSF) analysis. In summary, in cases with stable neurologic conditions, a trial administration of intravenous penicillin with follow-up imaging may be the optimal treatment option, and in cases with rapid progression or acute exacerbation, a surgical resection together with systemic antibiotic treatment for syphilis after surgery may be the best treatment strategy.
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Síndrome de Brown-Séquard/complicaciones , Neurosífilis/complicaciones , Médula Espinal/patología , Adulto , Anciano , Síndrome de Brown-Séquard/diagnóstico por imagen , Femenino , Humanos , Inflamación/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neurosífilis/diagnóstico por imagen , Médula Espinal/diagnóstico por imagen , Resultado del TratamientoRESUMEN
In this work, a new electrochemical immunosensor was developed for prion protein assay based on hybridization chain reaction (HCR) with hemin/G-quadruplex DNAzyme for signal amplification. In this amplification system, the hemin/G-quadruplex DNAzyme simultaneously mimicked the biocatalytic functions for H2O2 reduction and L-cysteine oxidation. In the presence of L-cysteine, the hemin/G-quadruplex catalyzed the oxidation of L-cysteine to L-cystine. At the same time, H2O2 was produced under the oxygen condition. Then, the hemin/G-quadruplex could quickly catalyze the reduction of H2O2, mimicking the catalytic performance of horseradish peroxidase (HRP). Under the optimal conditions, the immunosensor showed a wide linear response range from 0.5â¯pg/mL to 100â¯ng/mL with the low detection limit of 0.38â¯pg/mL (3σ). By changing the specific antibody, this strategy could be easily extended to detect the infectious isoform of prion (PrPSc) and other proteins. Based on its good analytical performance, the developed method shows great potential applications in diagnosis of prion diseases at presymptomatic stage and bioanalysis.
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Técnicas Biosensibles , ADN Catalítico/química , G-Cuádruplex , Hemina/química , Inmunoensayo , Proteínas Priónicas/análisis , Anticuerpos/química , Materiales Biomiméticos/química , Biotina/química , Cisteína/química , Cistina/química , Electrodos , Peroxidasa de Rábano Silvestre/química , Peróxido de Hidrógeno/química , Límite de Detección , Oxidación-Reducción , Soluciones , Estreptavidina/química , Agua/químicaRESUMEN
Based on Co-Co Prussian blue analogue (Co-Co PBA), a novel immunosensor has been developed for sensitive detection of prion protein (PrPC). Gold nanoparticles (AuNPs)-modified Co-Co PBA nanocubes (PBA-AuNPs) worked as a support of the antibody (Ab2) of PrPC to obtain Ab2-PBA-AuNPs composite and also as the signal source for PrPC assay. When PrPC existed, Ab2-PBA-AuNPs could be introduced to the surface of another antibody of PrPC (Ab1) modified AuNPs/GC electrode (the gold nanoparticles-modified glassy carbon electrode) through specific antigen-antibody interaction between PrPC and its antibodies to form the Ab1-PrPC-Ab2 sandwich structure. With the help of KOH aqueous solution, PBA generated a large DPV response. The response peak currents were linear with the logarithmic values of the concentration of PrPC in the range from 0.075pgmL-1 to 100pgmL-1 with the detection limit of 0.014pgmL-1. Also, the immunosensor showed good selectivity and reproducibility. Based on the simple sensing structure and good analytical performance, the developed immunosensor may have promising applications in practical assay of infectious isoform of prion (PrPSc) and other proteins by simply changing the related antibody.
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Técnicas Biosensibles , Técnicas Electroquímicas , Ferrocianuros/química , Inmunoensayo , Nanopartículas del Metal/química , Proteínas PrPC/análisis , Anticuerpos Inmovilizados/química , Cobalto/química , Electrodos , Oro/química , Límite de Detección , Nanopartículas del Metal/ultraestructura , Proteínas PrPC/inmunología , Unión Proteica , Soluciones , AguaRESUMEN
PURPOSE: Neoadjuvant chemotherapy (NAC) plays a pivotal role in the treatment of locally advanced breast cancer (LABC); however, breast cancer is a heterogeneous disease, individual responses to chemotherapy are highly variable. Therefore, the purpose of the current research is to identify biomarkers that can predict the chemotherapeutic response. PATIENTS AND METHODS: We recruited 78 patients with primary breast cancer who underwent taxane- and anthracycline-based NAC; these patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The microRNA microarray was conducted to explore differentially expressed miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) further validated the relationship between miR-4530 and chemosensitivity in breast cancer patients. RESULTS: No significant differences were observed between the two groups regarding the clinicopathological characteristics. miR-4530 showed the most potential involving breast cancer chemosensitivity. Mechanically, RUNX2 was identified one of the direct targets of miR-4530 and responsible for breast cancer chemosensitivity. CONCLUSION: Our results revealed that elevated serum miR-4530 levels may sensitize breast cancer to taxane- and anthracycline-based NAC by suppressing RUNX2; therefore, this miRNA has the potential to be a new biomarker for predicting breast cancer chemosensitivity.
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Taking TdT-mediated hemin/G-quadruplex DNAzyme nanowires as NADH oxidase and HRP-mimicking DNAzyme, a novel DNA-based electrochemical method has been developed for sensitive and selective assay of alkaline phosphatase (AP) activity. The double-stranded DNA (dsDNA) probe consisted of thiol-functionalized DNA1 and 3'-phosphorylated DNA2, was immobilized on a gold nanoparticles (AuNPs) modified glassy carbon (GC) electrode. In the presence of AP, 3'-phosphoryl end of DNA2 was dephosphorylated. Terminal deoxynucletidyl transferase (TdT) catalyzed the sequential addition of deoxynucleotides (dTTPs) at 3'-OH end of DNA2 to extend DNA2 with a poly-T sequence. Then, G-rich DNA3 strand hybridized with the poly-T sequence of DNA2. Upon addition of hemin, the hemin/G-quadruplex DNAzyme was formed. In the presence of NADH, the hemin/G-quadruplex DNAzyme oxidased NADH to NAD+, accompanied by the formation of H2O2 which was further catalyzed by hemin/G-quadruplex DNAzyme (served as a HRP-mimicking DNAzyme) with the thionine (Thi) as electron transfer mediator, leading to the amplified electrochemical signal. Under optimized conditions, the response peak current was linear with the concentration of AP in the range from 0.1UL-1 to 5UL-1 with the detection limit of 0.03UL-1. Also, the developed biosensor possessed good selectivity, reproducibility and stability, and simple sensing structure, showing promising practical applications in AP activity assay.
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Fosfatasa Alcalina/análisis , ADN Catalítico/química , Técnicas Electroquímicas/métodos , G-Cuádruplex , Hemina/química , Nanocables/química , Fosfatasa Alcalina/sangre , Animales , Artemia/enzimología , ADN Nucleotidilexotransferasa/química , Pruebas de Enzimas/métodos , Humanos , Límite de Detección , Nanocables/ultraestructuraRESUMEN
Objective To explore the possible correlation between uric acid levels and leukoaraiosis (LA). Methods This cross-sectional study enrolled patients who presented with some neurological discomfort (e.g. dizziness, headache, mild cognitive impairment). Potential demographic and clinical risk factors associated with LA, including sex, age, hypertension, diabetes mellitus, smoking, alcohol consumption, dyslipidaemia, plasma fibrinogen, D-dimer, uric acid, and homocysteine, were investigated using univariate and multivariate logistic regression analyses. Results A total of 268 patients were enrolled in the study and divided into the LA group ( n = 164) and the non-LA group ( n = 104). Compared with the non-LA group, uric acid was significantly higher in the LA group (mean ± SD: 356.49 ± 121.85 µmol/l versus 289.96 ± 102.98 µmol/l). Multivariate logistic regression analyses showed that uric acid was an independent risk factor for LA (odds ratio 1.285; 95% confidence interval 1.062, 1.556). Conclusion Hyperuricaemia was an independent risk factor for leukoaraiosis in Chinese patients.
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Hiperuricemia/diagnóstico , Leucoaraiosis/diagnóstico , Ácido Úrico/sangre , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/fisiopatología , Pueblo Asiatico , Disfunción Cognitiva/fisiopatología , Estudios Transversales , Diabetes Mellitus/fisiopatología , Mareo/fisiopatología , Dislipidemias/fisiopatología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/metabolismo , Cefalea/fisiopatología , Homocisteína/sangre , Humanos , Hipertensión/fisiopatología , Hiperuricemia/sangre , Hiperuricemia/complicaciones , Hiperuricemia/etnología , Leucoaraiosis/sangre , Leucoaraiosis/complicaciones , Leucoaraiosis/etnología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Fumar/fisiopatologíaRESUMEN
Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.
Asunto(s)
Carcinoma Adenoide Quístico/terapia , Carcinoma Ductal de Mama/terapia , Neoplasias de la Mama Triple Negativas/terapia , Adulto , Anciano , Biomarcadores de Tumor/análisis , Carcinoma Adenoide Quístico/química , Carcinoma Adenoide Quístico/mortalidad , Carcinoma Adenoide Quístico/secundario , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/secundario , Diferenciación Celular , Distribución de Chi-Cuadrado , Bases de Datos Factuales , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores de Riesgo , Programa de VERF , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Breast-conserving surgery (BCS) including radiotherapy (RT) has been demonstrated to provide at least equivalent prognosis to mastectomy in early-stage breast cancer. However, studies on triple-negative breast cancer (TNBC) patients are relatively scarce. The current population-based study aimed to investigate the distinct outcomes between BCS+RT and mastectomy in patients with TNBC. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled 11,514 female TNBC cases diagnosed during the years 2010-2013. Those patients were subdivided into BCS+RT (5,469) and mastectomy groups (6,045), and we conducted a survival comparison between the two groups. The endpoints were breast cancer-specific survival (BCSS) and overall survival (OS). In the overall cohort, patients with BCS+RT exhibited distinctly better breast cancer-specific survival (BCSS) (log-rank, p < 0.001) and overall survival (OS) (log-rank, p < 0.001) than did mastectomy patients. When stratifying the TNBC patients according to age, histology grade, TNM stage, tumor size, and lymph node (LN) status, most patients in the BCS+RT group presented with better survival than did the patients in the mastectomy group, except for the grade I (log-rank, p = 0.830, both BCSS and OS) and stage I (log-rank, BCSS, p = 0.127; OS, p = 0.093) patients. In addition, after adjusting for confounding variables by multivariable Cox proportional hazard analysis, BCS+RT still tended to present with higher BCSS and OS. In conclusion, from our study on SEER data, BCS+RT displayed elevated BCSS and OS in TNBC patients compared to mastectomy, at least equally. Our study provided further evidence for surgeons that BCS with RT is available for TNBC patients.