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1.
Phys Rev Lett ; 132(1): 010602, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38242678

RESUMO

As a hybrid of artificial intelligence and quantum computing, quantum neural networks (QNNs) have gained significant attention as a promising application on near-term, noisy intermediate-scale quantum devices. Conventional QNNs are described by parametrized quantum circuits, which perform unitary operations and measurements on quantum states. In this Letter, we propose a novel approach to enhance the expressivity of QNNs by incorporating randomness into quantum circuits. Specifically, we introduce a random layer, which contains single-qubit gates sampled from a trainable ensemble pooling. The prediction of QNN is then represented by an ensemble average over a classical function of measurement outcomes. We prove that our approach can accurately approximate arbitrary target operators using Uhlmann's theorem for majorization, which enables observable learning. Our proposal is demonstrated with extensive numerical experiments, including observable learning, Rényi entropy measurement, and image recognition. We find the expressivity of QNNs is enhanced by introducing randomness for multiple learning tasks, which could have broad application in quantum machine learning.

2.
J Pediatr Nurs ; 75: e1-e9, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38212174

RESUMO

PURPOSE: Pediatric cancer is a significant health concern in China, and evaluating the impact of cancer and its treatment on the well-being of young patients is essential for both clinical care and research purposes. This study aimed to psychometrically validate the Patient-reported Outcomes Measurement Information System Pediatric-25 Profile (PROMIS-Pediatric-25) among Chinese children with cancer. DESIGN AND METHODS: We enrolled a group of 114 children living with cancer between the ages of 8 and 17. Each participant completed questionnaires that covered sociodemographic and clinical information and the PROMIS-Pediatric-25. The floor and ceiling effect was examined. Cronbach's alpha and split-half coefficient were examined to determine the reliability. Factor structure was explored by factor analysis. Three assumptions of Rasch model-based item response theory (IRT) were assessed. Differential item functioning (DIF) was investigated concerning factors of gender, diagnosis, and treatment stage. RESULTS: The floor or ceiling effects were detected for six domains. The reliability was found to be excellent. Furthermore, the factor structure of these six domains was validated. Our analysis confirmed that the assumptions required for IRT were met with acceptable unidimensionality, local independence, and good monotonicity. Additionally, we observed measurement equivalence, with outstanding levels of DIF across factors such as gender, diagnosis, and treatment stage. CONCLUSION: PROMIS-Pediatric 25 is a highly reliable and valid instrument for evaluating key domains of health-related quality of life in Chinese pediatric cancer patients. PRACTICE IMPLICATION: Nursing practice could engage the PROMIS-Pediatric 25 for accurate and quick children symptom and function assessment.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Criança , Adolescente , Reprodutibilidade dos Testes , Psicometria , Inquéritos e Questionários , Neoplasias/diagnóstico , Neoplasias/terapia
3.
Molecules ; 29(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38675511

RESUMO

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.


Assuntos
Antioxidantes , Astragalus propinquus , Medicamentos de Ervas Chinesas , Antioxidantes/farmacologia , Antioxidantes/química , Astragalus propinquus/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Astrágalo/química , Estresse Oxidativo/efeitos dos fármacos , Animais , Flavonoides/química , Flavonoides/farmacologia , Medicina Tradicional Chinesa , Saponinas/farmacologia , Saponinas/química
4.
Cent Eur J Immunol ; 49(1): 77-90, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812606

RESUMO

Esophageal cancer is considered one of the most significant challenges to public health worldwide. While various therapeutic options exist for esophageal cancer, including chemotherapy, radiotherapy, and surgery, several adverse effects of these medications have been reported. Therefore, a new generation of therapeutic lines should be applied to minimize complications. In this regard, immunotherapy is a novel approach that aims to kill tumor cells directly by targeting them. Specifically, monoclonal antibodies can target specific markers of esophageal cancer tumor cells, keeping other normal cells safe. Multiple monoclonal antibodies optimized for esophageal cancer, such as pembrolizumab, ramucirumab, trastuzumab, nivolumab, and ipilimumab, are available. On the other hand, esophageal cancer tumor cells express a specific inhibitory ligand and its receptor called programmed cell death, which can suppress T cell immune responses. This receptor provides an inhibitory signal, causing the highest expression of the PD-L1 ligand on tumor cells. The outcomes of this interaction lead to the suppression of the activation and function of T lymphocytes. Therefore, immunotherapy for esophageal cancer targeting the PD-1/PD-L1 pathway has shown a remarkable correlation with cancer care. This study presents a comprehensive review of the latest findings related to immunotherapy in esophageal cancer.

5.
Anal Chem ; 95(33): 12487-12496, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37534990

RESUMO

Loop-mediated isothermal amplification (LAMP) is a commonly used alternative to PCR for point-of-care detection of nucleic acids due to its rapidity, sensitivity, specificity, and simpler instrumentation. While dual-labeled TaqMan probes are widely used in PCR for single-nucleotide polymorphism (SNP) genotyping, real-time LAMP primarily relies on turbidimetry or intercalator fluorescence measurements, which can be non-specific and generate false-positive results. In this study, we propose a closed-tube, dual-labeled RNA-modified probes and RNase H II-assisted real-time LAMP (RART-LAMP) method for SNP genotyping. Our findings indicate that (1) fluorescence signals were predominantly derived from probe hydrolysis rather than hybridization, (2) temperature-controlled hybridization between the probe and template ensured the specificity of SNP analysis, and (3) RNase H II hydrolysis between the target containing SNP sites and probes did not exhibit sequence specificity. Our RART-LAMP approach demonstrated excellent performance in genotyping C677T clinical samples, including gDNA extracted from blood, saliva, and swabs. More importantly, saliva and swab samples could be directly analyzed without any pretreatment, indicating promising prospects for nucleic acid analysis at the point of care in resource-limited settings.


Assuntos
Técnicas de Amplificação de Ácido Nucleico , Polimorfismo de Nucleotídeo Único , Genótipo , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase , Hibridização de Ácido Nucleico
6.
Pacing Clin Electrophysiol ; 46(12): 1595-1598, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36938703

RESUMO

BACKGROUNDS: Two technologies, cardiac contractility modulation (CCM) and subcutaneous implantable cardioverter-defibrillator (S-ICD), can be successfully combined and applied to patients with advanced heart failure (HF) with reduced left ventricular ejection fraction (LVEF). CASE REPORT: We reported a case of a 51-year-old man with reduced ejection fraction (LVEF = 33%) and a narrow QRS complex who first underwent simultaneous implantation of CCM and S-ICD. CONCLUSION: Our case report aimed to reveal that the simultaneous implantation of CCM and S-ICD could be successfully used in patients with advanced HF, which could significantly improve the clinical symptoms of such patients during one surgery.


Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca , Marca-Passo Artificial , Disfunção Ventricular Esquerda , Masculino , Humanos , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda , Resultado do Tratamento , Desfibriladores
7.
Environ Monit Assess ; 195(10): 1146, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668826

RESUMO

Drilling fluid waste is produced by oil and gas industry operations and can potentially cause serious environmental pollution and energy consumption if not properly treated. Currently, there are several treatment methods available for drilling fluid waste such as bioremediation, thermal treatment, solidification/stabilization treatment, electrochemical remediation, physiochemical treatment, and supercritical fluid treatment. However, selecting an adequate method to treat drilling fluid waste is a critical consideration. The objective of this work is to analyze the problem of drilling fluid waste pollution and treatment methods, establish a drilling fluid waste treatment decision index system that takes into account various factors, and apply the intuitionistic fuzzy-based entropy weight method (EWM)-technique for order of preference by similarity to ideal solution (TOPSIS) method to make a multi-attribute group decision on drilling fluid waste treatment methods. The method is then applied to the WBQ004-1-H1 drilling project as an example for comprehensive analysis. The final decision results show that A3 (0.566) > A1 (0.537) > A6 (0.526) > A5 (0.485) > A4 (0.478) > A2 (0.447), so the solidification/stabilization treatment is the most suitable method for this project, providing new insights into selecting drilling fluid waste treatment methods in actual projects.


Assuntos
Tomada de Decisões , Monitoramento Ambiental , Entropia , Poluição Ambiental , Tecnologia
8.
Clin Immunol ; 238: 109013, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35436628

RESUMO

Short-chain fatty acids (SCFAs), metabolites of intestinal microorganisms, have been linked to the occurrence and development of a variety of disorders, including cardiovascular disease (CVD), which is frequently accompanied by a sustaining inflammatory response and aberrant angiogenesis. Accumulating evidence from the study emphasizes that SCFAs are closely connected with the activation of the NLRP3 inflammasome (NACHT, LRR, and PYD domains-containing protein 3) and the process of angiogenesis. This review summarizes emerging literature on the impact of SCFAs on various physiological processes, with a subtle attention on the interaction between SCFAs and CVD (especially atherosclerosis, myocardial infarction, and hypertension), SCFAs and NLRP3 inflammasome, as well as SCFAs and angiogenesis. As a result, we speculate that it is convincing that SCFAs play a mediating role in the microbiota-inflammasome-angiogenesis-CVD axis, opening up a new horizon to investigate the function or level of SCFAs as a therapeutic strategy for CVD.


Assuntos
Doenças Cardiovasculares , Inflamassomos , Ácidos Graxos Voláteis/metabolismo , Humanos , Inflamassomos/metabolismo , Intestinos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
9.
Anal Chem ; 94(38): 13052-13060, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36094399

RESUMO

Genotyping of folate metabolism genes is of great importance in disease diagnosis and prevention. However, most current detection methods used for folate metabolism gene genotyping are based on sequencing and chips, which suffer from a high cost and laborious and time-consuming procedures. Herein, we reported a multiplex asymmetric PCR-HRM strategy for identifying genotypes of folate metabolism genes in a single tube. The proposed multiplex PCR-HRM assay has been successfully applied to identify the genotypes of folate metabolism genes, methylene tetrahydrofolate reductase (C677T, A1298C) and methionine synthase reductase A66G, on 1 µL of genomic DNA (gDNA) samples directly released from blood specimens, and the genotyping results were 100% consistent with the results of sequencing. The assay allows us to accurately detect the genotypes of gDNA with the detection limit down to 1 ng, which meets the clinical requirement. What is more, the capacity of resistance to aerosol pollution of the multiplex asymmetric PCR-HRM biosensing was first addressed and has been evaluated as it can withstand contamination of roughly 12.5-25% interfering nucleic acids. Because of the advantages of multiplex detection, high accuracy, and resistance to aerosol pollution and having no open tube procedure, this approach would pave the way for establishing a fast and cost-effective platform for folate metabolism gene genotyping and other SNP genotyping in clinical diagnostics.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2) , Ácidos Nucleicos , Ferredoxina-NADP Redutase , Ácido Fólico/metabolismo , Genótipo , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Reação em Cadeia da Polimerase Multiplex , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real
10.
Theor Appl Genet ; 135(12): 4245-4259, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36181524

RESUMO

KEY MESSAGE: A FT/TFL1 subfamily gene, rice CENTRORADIALIS 2, also known as RCN1, regulates seed germination and increase salt tolerance via ABA-mediated pathway. The ABA synthesis and metabolism related genes were changed relative expression levels. Seed germination is a complex biological process that is affected by many factors. Although a number of germination-related genes have been reported, the molecular mechanism of germination regulation has not yet been fully elucidated. Here, we reported that the rice OsCEN2 gene can negatively regulate seed germination. The germination speed of OsCEN2-RNAi seeds was significantly faster while that of OsCEN2-overexpression (OE) seeds was slower than that of the wild type (WT). The results of qRT-PCR showed that the OsCEN2 expression was increased in the early stage of seed germination. Exogenous application of abscisic acid (ABA) on seeds and seedlings showed that OsCEN2-OE seeds and seedlings were highly sensitive to ABA during germination and post-germination growth, respectively. The determination of endogenous ABA content in seeds also showed that the ABA content of OsCEN2-RNAi seeds was lower, while that of OsCEN2-OE seeds was higher. Moreover, the transgenic plants changed salt tolerance because of the altered ABA level. In addition, differences were also observed in the expression of genes related to ABA synthesis and metabolism in the seeds of OsCEN2-transgenic lines. This study reveals that OsCEN2 regulates the germination speed by affecting the content of ABA during seed germination and provides a theoretical basis for research on rice direct seeding.


Assuntos
Arabidopsis , Oryza , Ácido Abscísico/metabolismo , Germinação/genética , Tolerância ao Sal/genética , Sementes/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas
11.
Anal Bioanal Chem ; 414(7): 2493-2503, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35171297

RESUMO

Sol-gel materials have been widely used for solid-phase microextraction (SPME) coatings due to their outstanding performance; in contrast, sol-gel SPME coatings have seldom been used for in vivo sampling. The main reason is that their matrix compatibility is unclear. In order to promote the application of this type of coating and accelerate the development of in vivo SPME, in this study, the matrix compatibility of several typical sol-gel coatings was assessed in plasma and whole blood using phthalic acid esters as analytes. The service life of five kinds of sol-gel coatings was among 20-35 times in undiluted plasma, while it was 27 times for a homemade commercial polydimethylsiloxane coating, which indicates good matrix compatibility of sol-gel coatings in untreated plasma. The sol-gel hydroxy-terminated silicone oil/methacrylic acid fiber achieved the highest extraction ability among all of the fibers, and it was tested in pig whole blood. It could be continuously used for at least 22 times, demonstrating good potential for in vivo sampling. Subsequently, a direct-immersion SPME/gas chromatography-flame ionization detection method was established for the determination of 5 phthalic acid esters in blood. Compared with other methods reported in the literature, this method is rapid, simple, sensitive, and accurate, and does not need expensive instruments or tedious procedures. A simulation system of animal blood circulation was constructed to verify the practicability of sol-gel SPME coatings in animal vein sampling. The result illustrated the feasibility of that coating for in vivo blood sampling, but a more accurate quantification calibration approach needs to be explored.


Assuntos
Ácidos Ftálicos , Microextração em Fase Sólida , Animais , Cromatografia Gasosa/métodos , Ésteres , Microextração em Fase Sólida/métodos , Suínos
12.
J Biochem Mol Toxicol ; 36(11): e23182, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35938691

RESUMO

Aberrant expression of microRNA-497 (miR-497) is associated with tumor progression, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we report that miR-497 expression is downregulated in esophageal squamous cell carcinoma (ESCC) clinical samples. Consistently, upregulation of miR-497 inhibits ESCC cell malignant properties and tumor growth in vivo. Importantly, we uncovered that miR-497 upregulation suppressed ESCC cell growth and tumor growth by inhibiting Smurf2. Mechanistically, we showed that Smurf2 was a target of miR-497, and mediated YY1 expression to elevate HIF2α expression, thereby enhancing the malignancy of ESCC cells. Together, our study uncovered the role of the miR-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis, which might provide potential therapeutic targets for human ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , MicroRNAs/genética , Linhagem Celular Tumoral , Regulação para Cima , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Invasividade Neoplásica/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
13.
Appl Opt ; 61(28): 8376-8381, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256151

RESUMO

Porous ZnO nanosheets (ZnO NSs) may play an important role in self-powered UV photodetectors due to their excellent properties, and their porosity feature affects the photoresponse performance greatly. Porous ZnO NSs were prepared by the hydrothermal method followed with a one-step annealing treatment. The effects of the annealing temperature on the microstructure and photoresponse of porous ZnO NSs and n-ZnO NSs/p-PEDOT:PSS self-powered UV photodetectors were investigated. The results show that the pore density and size of ZnO NSs can be tuned by changing the annealing temperature. At an optimum annealing temperature of 450°C, ZnO NSs exhibit greater absorption capacity for the suitable pore density and size. Meanwhile, more crystal defects due to surface contractile properties increase the number of photogenerated carriers. On this basis, the n-ZnO NSs/p-PEDOT:PSS photodetector presents a larger photocurrent and fast photodetection speed without external bias voltage, indicating the self-powered performance. The higher light absorption and large number of electron-hole pairs resulting from dense pores and surface defects in porous ZnO NSs might account for the enhanced performances.

14.
BMC Anesthesiol ; 22(1): 124, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477377

RESUMO

BACKGROUND: The complications of postoperative pain, such as hypertension, hypermetabolism, irritability, and postoperative cognitive dysfunction, significantly affect the postoperative rehabilitation of elderly patients. Intrathecal morphine prolongs analgesia after surgery, but has been implicated in nausea and vomiting, pruritus, postoperative respiratory depression, or apneic episodes. The present study explored the effect and safety of low-dose morphine used adjunctively with bupivacaine during single spinal anesthesia or sufentanil patient-controlled intravenous analgesia (PCIA) in elderly patients with hip fracture surgery. Since elderly patients often need anticoagulant therapy in the early postoperative period, single spinal anesthesia was involved in completing the operation in this study. METHODS: Eighty elderly patients aged 70-85 years who underwent elective hip fracture surgery with single spinal anesthesia were divided into two groups, 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of morphine (morphine group, group M) and 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of sufentanil PCIA (sufentanil group, group S). The analgesia scores using the visual analogue scale (VAS), the Brinell comfort scale (BCS) were evaluated at 6, 12, 24, and 48 h after operation, and adverse reactions were recorded such as nausea and vomiting, pruritus, sedation, respiratory depression, and POD (postoperative delirium) with Delirium Rating Scale-r 98. RESULTS: Within 24 h after operation, the analgesic and BCS scores of group M were better than those of group S (P < 0.05). Group M had higher frequency of skin pruritus than group S within 24 h, and the difference was statistically significant. The incidence of POD in group M (2 cases) was lower than that in group S (6 cases) (5.71% vs 18.18%) (P < 0.05) with the DRS-r 98 scores. No significant difference was observed in nausea and vomiting between the two groups, and the difference of severe respiratory depression was not found in both groups. CONCLUSION: Compared with sufentanil PCIA, low-dose intrathecal morphine has a satisfactory analgesic effect, and little effect on the patient's cognitive function with low medical cost. Under effective respiratory monitoring, it can be used safely and effectively in elderly patients with hip fracture. TRIAL REGISTRATION: Registered with the Chinese Clinical Trial Registry under ChiCTR2100042706 . 26/01/2021.


Assuntos
Raquianestesia , Delírio , Fraturas do Quadril , Insuficiência Respiratória , Idoso , Analgesia Controlada pelo Paciente , Analgésicos Opioides , Bupivacaína , Delírio/tratamento farmacológico , Fraturas do Quadril/cirurgia , Humanos , Morfina , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Complicações Pós-Operatórias/induzido quimicamente , Prurido/induzido quimicamente , Prurido/epidemiologia , Insuficiência Respiratória/induzido quimicamente , Sufentanil/efeitos adversos , Vômito/induzido quimicamente
15.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1942-1954, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534265

RESUMO

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.


Assuntos
Medicamentos de Ervas Chinesas , Anticoagulantes/farmacologia , Coagulação Sanguínea , Desenho de Fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular
16.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4436-4445, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046873

RESUMO

This study aims to investigate the effect of atractylenolide Ⅲ(ATL-Ⅲ) on hydrogen peroxide(H_2O_2)-induced endoplasmic reticulum stress and apoptosis of H9 c2 cells via the ROS/GRP78/caspase-12 signaling pathway.The binding activity of ATL-Ⅲ to GRP78 was determined by molecular docking.The result showed that ATL-Ⅲ had a good binding activity to GRP78, and the binding activity of ATL-Ⅲ was stronger than that of its specific inhibitor.The endoplasmic reticulum stress model of H9 c2 was established by H_2O_2(100 µmol·L~(-1)) treatment.Five groups were designed: blank control group, model group, and ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) groups.Apoptosis was detected by Hoechst/PI double staining and flow cytometry.The levels of superoxide dismutase(SOD), malondialdehyde(MDA), and lactate dehydrogenase(LDH) were measured by colorimetry.The levels of reactive oxygen species(ROS) and calcium(Ca~(2+)) in cytoplasm were determined by the fluorescence probe DCFH-DA and the calcium fluorescence probe Flou-4, respectively.The protein levels of GRP78, caspase-12, and caspase-3 were determined by Western blot, and the mRNA levels of GRP78 and caspase-12 by RT-qPCR.N-acetyl-L-cysteine(NAC) and 4-phenylbutyric acid(4-PBA) were respectively used to inhibit ROS and GRP78, and then the mechanism of ATL-Ⅲ in protecting the cells from endoplasmic reticulum stress induced by H_2O_2 were deduced.ATL-Ⅲ(15, 30, and 60 µmol·L~(-1)) decreased the apoptosis rate and ROS, MDA, and LDH levels(P<0.01), increased the SOD activity(P<0.01), and down-regulated the protein levels of GRP78, caspase-12, and caspase-3 and the mRNA levels of GRP78 and caspase-12(P<0.05).The addition of NAC decreased the apoptosis rate and ROS, MDA, GRP78, caspase-12, and caspase-3 levels(P<0.01), while it elevated the SOD level(P<0.01).The addition of 4-PBA also decreased the apoptosis rate and the levels of GRP78, caspase-12, caspase-3, and Ca~(2+)(P<0.01).The effect of inhibitors were consistent with that of ATL-Ⅲ.In conclusion, ATL-Ⅲ can protect H9 c2 cardiomyocytes by regulating ROS/GRP78/caspase-12 signaling pathway to inhibit H_2O_2-induced endoplasmic reticulum stress and apoptosis.


Assuntos
Cálcio , Chaperona BiP do Retículo Endoplasmático , Apoptose , Cálcio/farmacologia , Caspase 12/genética , Caspase 12/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Estresse do Retículo Endoplasmático , Lactonas , Simulação de Acoplamento Molecular , RNA Mensageiro , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos , Transdução de Sinais , Superóxido Dismutase/metabolismo
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(10): 966-968, 2021 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-34625933

RESUMO

OBJECTIVE: To detect pathogenic variant in a child featuring Usher syndrome type II. METHODS: Peripheral blood samples of the child and his parents were collected for the analysis of variants of hearing impairment-related genes. The findings were verified in 100 individuals with normal hearing. RESULTS: The child was found to harbor compound heterozygous variants of the USH2A gene, namely c.8224-1G>C in intron 41 and c.5678C>G(p.Ser1893X) in exon 28, which were inherited respectively from his mother and father. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.8224-1G>C and c.5678C>G(p.Ser1893X) variants of USH2A gene were predicted to be pathogenic(PVS1+PM2+PM3). CONCLUSION: The compound heterozygous variants c.8224-1G>C and c.5678C>G of the USH2A gene probably underlay the disease in this child. Above finding has enriched the spectrum of USH2A gene variants.


Assuntos
Síndromes de Usher , Criança , Éxons , Proteínas da Matriz Extracelular/genética , Família , Humanos , Íntrons , Estados Unidos , Síndromes de Usher/genética
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 569-572, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096028

RESUMO

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) to verify a fetus with partial 18p deletion signaled by non-invasive prenatal testing. METHODS: G-banding chromosomal karyotyping analysis was carried out on amniotic fluid sample of the fetus and peripheral blood samples from the parents. Amniotic DNA was also subjected to CMA analysis. The fetus was also subjected to systematic ultrasound scan. RESULTS: The fetus was found to have a karyotype of 46,XX,18p+. CMA has revealed a 5 Mb deletion at 18p11.32-p11.31, a 2.9 Mb duplication at 18p11.31-p11.23, and a 2.5 Mb duplication at 18p11.23-p11.22. No chromosomal aberration or microdeletion/microduplication was detected in either parent. CONCLUSION: Non-invasive prenatal testing and CMA are both sensitive for the detection of chromosomal microdeletions and microduplications. CMA can help with clarification of genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.


Assuntos
Deleção Cromossômica , Diagnóstico Pré-Natal , Cromossomos , Feminino , Feto , Humanos , Cariotipagem , Gravidez
19.
IUBMB Life ; 72(3): 401-412, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31743955

RESUMO

The expression of long noncoding RNAs (lncRNAs) is closely associated with cancer development and progression, making these lncRNAs potentially novel therapeutic targets. In this study, we aimed to explore the potential function of lncRNA-uc061hsf.1 in esophageal squamous cell carcinoma (ESCC). The expression of lncRNA-uc061hsf.1 in ESCC tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, and metastasis were detected via CCK-8, flow cytometry, and Transwell assays. The interaction between p53 and lncRNA uc061hsf.1 was analyzed using luciferase reporter gene and qRT-PCR. Through this approach, we identified the novel lncRNA uc061hsf.1, which was expressed in low level in ESCC and was correlated with lymph node metastasis and poor differentiation in ESCC patients. Knockdown or overexpression of lncRNA uc061hsf.1 in ESCC cells promoted or inhibited cell proliferation and metastasis, respectively. Mechanistically, lncRNA uc061hsf.1 was induced by p53, and luciferase reporter gene confirmed that lncRNA uc061hsf.1 was a direct transcriptional target of p53. We further found that uc061hsf.1 was able to regulate expression of the transcription factor FoxA1, thereby potentially influencing tumor cell migration. In conclusion, these results suggest that p53-regulated lncRNA uc061hsf.1 is a cancer suppressor gene which is associated with tumor progression in ESCC.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Metástase Linfática/genética , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genética , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
20.
Cancer Cell Int ; 20: 47, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32063748

RESUMO

BACKGROUND: This study aimed to investigate the clinical characteristics of miR-450b-3p in the patients of gastric cancer (GC), and further explore whether miR-450b-3p could inhibit the proliferation of GC cells via regulating KLF7. METHODS: Real-time quantitative PCR (qRT-PCR) was performed to detect the expression level of miR-450b-3p in 48 GC patients of tumor tissue and paracancerous tissue specimens collected, and the associations between miR-450b-3p and the clinical characteristics of GC patients were analyzed. Meanwhile, the expression of miR-450b-3p in GC cell lines was verified using qRT-PCR. miR-450b-3p overexpression vectors was constructed in GC cell lines including AGS and BGC-823, and then CCK-8 cell proliferation assay, Plate colony formation assay and EdU assay were applied to analyze the biological function of miR-450b-3p in GC cell lines. RESULTS: The results of qRT-PCR showed that the expression level of miR-450b-3p in GC tissues was lower than that in paracancerous tissues, and the difference was statistically significant. Compared with GC patients with high-miR-450b-3p expression, these GC patients with low-miR-450b-3p expression had a higher pathological stage and tumor size. Subsequently, the proliferation ability of GC cells in miR-450b-3p mimic was significantly decreased when comparing with the NC mimic. In addition, qRT-PCR indicated that the expression level of KLF7 significantly decreased after miR-450b-3p mimic. Therefore, it was demonstrated that miR-450b-3p might inhibit the malignant progression of GC via modulating KLF7. Bioinformatics analysis and dual luciferase reporter suggested miR-450b-3p was bound to KLF7. Finally, the results of the reverse experiment confirmed that overexpression of KLF7 could reverse miR-450b-3p mimic induced-inhibition of GC malignant progression. CONCLUSIONS: Generally, miR-450b-3p significantly down-regulated in GC tissues and cell lines, and was associated with the pathological stage and tumor size of GC patients. Meanwhile, miR-450b-3p inhibited cell proliferation in GC via modulating KLF7.

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