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1.
Artículo en Inglés | MEDLINE | ID: mdl-38401093

RESUMEN

Objective: Analyzing the impact of nursing workforce development, training and standardization on hybrid operating theatres. Methods: Thirty nurses in the mixed operating room of the First Affiliated Hospital of Nanchang University from January 2021 to December 2021 were selected as the control group to receive routine nursing management and training methods and another thirty nurses were selected as the experimental group to receive nursing team construction, training and standardized management based on conventional methods. Nurses' theoretical and operational scores, nurses' satisfaction, surgeon satisfaction with nurses, and nursing service quality scores were compared between two groups at baseline and after intervention. Results: After the intervention, nurses in both groups had a significant improvement in theoretical and operational scores than those at baseline, and nurses in the experimental group had better scores than those in the control group, The difference was statistically significant (P = .002, P = .004). Nursing quality of surgical preparation, environmental management, surgical safety, and instrument management in the intervention group were significantly better than those at baseline and better than those in the control group. The difference was statistically significant (P = .001, P = .001, P = .001, P = .001). Satisfaction of nurses and doctors in the intervention group was significantly better than those at baseline and better than those in the control group. The difference was statistically significant (P = .002, P = .001). Conclusion: The effect of nursing team construction and training and standardized management of hybrid operating Room was ideal, which can improve nurses' theoretical knowledge and practical skills, and enhance the satisfaction of nurses and surgeons, providing patients with higher quality nursing services, which is worth adopting.

2.
Cancer Cell Int ; 23(1): 164, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37568192

RESUMEN

OBJECTIVE: Systemic chemotherapy is the first-line therapeutic option for head and neck squamous cell carcinoma (HNSCC), but it often fails. This study aimed to develop an effective prognostic model for evaluating the therapeutic effects of systemic chemotherapy. METHODS: This study utilized CRISPR/cas9 whole gene loss-of-function library screening and data from The Cancer Genome Atlas (TCGA) HNSCC patients who have undergone systemic therapy to examine differentially expressed genes (DEGs). A lipid metabolism-related clustered polygenic model called the lipid metabolism related score (LMRS) model was established based on the identified functionally enriched DEGs. The prediction efficiency of the model for survival outcome, chemotherapy, and immunotherapy response was evaluated using HNSCC datasets, the GEO database and clinical samples. RESULTS: Screening results from the study demonstrated that genes those were differentially expressed were highly associated with lipid metabolism-related pathways, and patients receiving systemic therapy had significantly different prognoses based on lipid metabolism gene characteristics. The LMRS model, consisting of eight lipid metabolism-related genes, outperformed each lipid metabolism gene-based model in predicting outcome and drug response. Further validation of the LMRS model in HNSCCs confirmed its prognostic value. CONCLUSION: In conclusion, the LMRS polygenic prognostic model is helpful to assess outcome and drug response for HNSCCs and could assist in the timely selection of the appropriate treatment for HNSCC patients. This study provides important insights for improving systemic chemotherapy and enhancing patient outcomes.

3.
Molecules ; 27(24)2022 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-36558170

RESUMEN

The fluorination strategy is one of the most efficient and popular molecular modification methods to develop new materials for organic photovoltaic (OPV) cells. For OPV materials, it is a broad agreement that fluorination can reduce the energy level and change the morphology of active layers. To explore the effect of fluorination on small molecule acceptors, we selected two non-fullerene acceptors (NFA) based bulk heterojunction (BHJ) films, involving PM6:Y6 and PM6:Y5 as model systems. The electron mobilities of the PM6:Y5 and PM6:Y6 BHJ films are 5.76 × 10-7 cm2V-1s-1 and 5.02 × 10-5 cm2V-1s-1 from the space-charge-limited current (SCLC) measurements. Through molecular dynamics (MD) simulation, it is observed that halogen bonds can be formed between Y6 dimers, which can provide external channels for electron carrier transfer. Meanwhile, the "A-to-A" type J-aggregates are more likely to be generated between Y6 molecules, and the π-π stacking can be also enhanced, thus increasing the charge transfer rate and electron mobility between Y6 molecules.

4.
Neurobiol Dis ; 156: 105408, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34082124

RESUMEN

Presbycusis contributes to cognitive decline and Alzheimer's disease. However, most research in this area involves clinical observations and statistical modeling, and few studies have examined the relationship between hearing loss and the molecular changes that lead to cognitive dysfunction. The present study investigated whether hearing loss contributes to dementia in the absence of aging and noise using a mouse model of severe bilateral hearing loss induced by kanamycin (1000 mg/kg) and furosemide (400 mg/kg). Immunohistochemistry, silver staining, immunofluorescence analysis, and Western blotting were used to observe pathological changes in different regions of the hippocampus in animals with hearing loss. Changes in the cognitive function of animals with hearing loss were assessed using the Morris water maze test. The results showed that neurons began to degenerate 60 days after hearing loss, and this degeneration was accompanied by structural disorganization and decreased neurogenesis. The level of phosphorylated tau increased over time. Increases in escape latency and distance traveled during the training phase of the Morris water maze test were observed 90 days after hearing loss. Activated microglia and astrocytes with increased levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected in the hippocampus. These results suggest that hearing loss alone causes neuronal degeneration, inhibition of neurogenesis, increased tau protein phosphorylation, and increased neuroinflammation in the hippocampus. Early intervention in individuals with hearing loss may reduce the risk of cognitive decline.


Asunto(s)
Demencia/patología , Pérdida Auditiva Sensorineural/patología , Hipocampo/patología , Neuronas/patología , Animales , Demencia/inducido químicamente , Demencia/metabolismo , Femenino , Furosemida/toxicidad , Pérdida Auditiva Sensorineural/inducido químicamente , Pérdida Auditiva Sensorineural/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Mediadores de Inflamación/metabolismo , Kanamicina/toxicidad , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteínas tau/metabolismo
5.
Anal Biochem ; 626: 114229, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33939971

RESUMEN

A colorimetric sensor based on gold nanoparticles (AuNPs) and single-stranded DNA (ssDNA) is a simple and rapid method for detecting foodborne pathogens. However, the colorimetric method employed in previous studies involved short ssDNA (<100 nucleotides), including the aptamer and PCR products, resulting in the high detection limit of this technique. In this study, a colorimetric sensor was developed based on long ssDNA of asymmetric PCR (aPCR) and non-functionalized AuNPs for detecting Salmonella Typhimurium (S. Typhimurium). In the presence of S. Typhimurium, the long ssDNA (547 nt) amplified by aPCR-protected AuNPs from NaCl-induced aggregation, while the solution retained a red color. After optimizing parameters, the limit of detection (LOD) of the colorimetric sensor was 2.56 CFU/mL with high specificity. Recovery studies showed its feasibility for detecting S. Typhimurium (102 CFU/mL, 104 CFU/mL, and 106 CFU/mL) in spiked lettuce samples. This colorimetric sensor provides new opportunities for the highly sensitive detection of bacteria in real food samples.


Asunto(s)
ADN Bacteriano/análisis , ADN de Cadena Simple/análisis , Oro/química , Nanopartículas del Metal/química , Reacción en Cadena de la Polimerasa/métodos , Salmonella typhimurium/genética , ADN de Cadena Simple/genética , Límite de Detección
6.
BMC Med Res Methodol ; 21(1): 192, 2021 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-34548029

RESUMEN

BACKGROUND: In follow-up studies, the occurrence of the intermediate event may influence the risk of the outcome of interest. Existing methods estimate the effect of the intermediate event by including a time-varying covariate in the outcome model. However, the insusceptible fraction to the intermediate event in the study population has not been considered in the literature, leading to effect estimation bias due to the inaccurate dataset. METHODS: In this paper, we propose a new effect estimation method, in which the susceptible subpopulation is identified firstly so that the estimation could be conducted in the right population. Then, the effect is estimated via the extended Cox regression and landmark methods in the identified susceptible subpopulation. For susceptibility identification, patients with observed intermediate event time are classified as susceptible. Based on the mixture cure model fitted the incidence and time of the intermediate event, the susceptibility of the patient with censored intermediate event time is predicted by the residual intermediate event time imputation. The effect estimation performance of the new method was investigated in various scenarios via Monte-Carlo simulations with the performance of existing methods serving as the comparison. The application of the proposed method to mycosis fungoides data has been reported as an example. RESULTS: The simulation results show that the estimation bias of the proposed method is smaller than that of the existing methods, especially in the case of a large insusceptible fraction. The results hold for small sample sizes. Besides, the estimation bias of the new method decreases with the increase of the covariates, especially continuous covariates, in the mixture cure model. The heterogeneity of the effect of covariates on the outcome in the insusceptible and susceptible subpopulation, as well as the landmark time, does not affect the estimation performance of the new method. CONCLUSIONS: Based on the pre-identification of the susceptible, the proposed new method could improve the effect estimation accuracy of the intermediate event on the outcome when there is an insusceptible fraction to the intermediate event in the study population.


Asunto(s)
Modelos Estadísticos , Sesgo , Simulación por Computador , Humanos , Método de Montecarlo , Tamaño de la Muestra
7.
Int J Clin Pharmacol Ther ; 59(9): 594-602, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33896448

RESUMEN

OBJECTIVE: To learn the safety profile of carbapenems and compare suspected adverse drug reactions (ADRs) among carbapenem classes by data mining the FDA adverse event reporting system (FAERS) database. MATERIALS: This retrospective study described the general characteristics of adverse drug event (ADE) reports related to carbapenems in the FAERS during 2015 - 2018. METHODS: The 95% confidence intervals (CIs) of proportional reporting ratio (PRR), the reporting odds ratio (ROR), and information component (IC) of Bayesian confidence propagation neural network (BCPNN) were calculated to identify potential safety signals. RESULTS: A total number of 5,899 reports associated with carbapenems were submitted to the FAERS from January 1, 2015 to December 31, 2018. The most frequently reported ADE associated with carbapenems was drug ineffective (10.51%). Serious ADEs and death associated with carbapenems were reported in 41.24 and 25.12%, respectively. Infections and infestations was the strongest signal detected in both meropenem and imipenem. Nervous system disorders and psychiatric disorders were strongly detected in ertapenem. Hepatobiliary disorders were common in doripenem patients. CONCLUSION: Carbapenem resistance is alarming in the United States, and carbapenem is more likely to be associated with serious and fatal ADEs among ß-lactam antibiotics. Both differences and similarities exist in the safety profile among carbapenems classes. Close attention should be paid to patients with special disease when administrated carbapenems.


Asunto(s)
Carbapenémicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Sistemas de Registro de Reacción Adversa a Medicamentos , Teorema de Bayes , Carbapenémicos/efectos adversos , Minería de Datos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Humanos , Estudios Retrospectivos , Estados Unidos/epidemiología , United States Food and Drug Administration
8.
J Clin Lab Anal ; 35(11): e24011, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34545635

RESUMEN

BACKGROUND: Interleukin 6 assays are useful in early detection of infections and risk stratification of critically ill patients, so an assay with a short turnaround-time and near-patient use is preferred. This study evaluated the performance of a new interleukin 6 assay, Pylon IL-6 assay, and explored its potential use in near-patient settings. METHODS: We carried out imprecision, linearity and comparison studies using serum and plasma samples according to CLSI EP guidelines. The stability of whole blood samples during storage was assessed. Furthermore, whole blood samples from pediatric patients with suspected infection were measured to evaluate the assay's diagnostic performance. RESULTS: The within-run CVs and total CVs of Pylon IL-6 assay were determined as 1.8% and 3.0% at 159.3 pg/ml and 3.5% and 4.7% at 8009.9 pg/ml, respectively. The method showed linearity between 1.5 and 42,854 pg/ml. The results of serum samples measured by Pylon assays correlated to those measured by Roche assays, as well as to those of matched whole blood samples measured by Pylon assays. IL-6 in whole blood was found stable for ~8 h at room temperature. Pylon IL-6 results of whole blood samples from 179 pediatric patients with suspected infection showed an AUC of 0.842 in diagnosis of bacterial infection. The turnaround time of Pylon IL-6 assay was only 1 h when using whole blood samples. CONCLUSION: The new assay demonstrated performance comparable to those performed on clinical laboratory instruments and can be used in near-patient settings with whole blood to reduce turnaround times.


Asunto(s)
Análisis Químico de la Sangre , Inmunoensayo , Interleucina-6/sangre , Análisis Químico de la Sangre/métodos , Análisis Químico de la Sangre/normas , Niño , Preescolar , Femenino , Humanos , Inmunoensayo/métodos , Inmunoensayo/normas , Lactante , Límite de Detección , Modelos Lineales , Masculino , Reproducibilidad de los Resultados
9.
Pak J Pharm Sci ; 33(1(Special)): 403-408, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32173634

RESUMEN

Inflammatory response that occur post-ischemia is a serious problem in the treatment of ischemic brain disease. MicroRNA-155 is a brain-specific or brain-enriched miRNA, which mediates inflammatory reactions in cerebral ischemic tissue by regulating inflammatory signal and the expression level of SOCS1. The present study was aimed to assess the effect of GuaLou GuiZhi Decoction (GLGZD) on miR-155 expression in activated microglia following inflammation and further explore the role of GLGZD on expression of the inflammation-related gene. BV2 cells were used to simulated by LPS to make the inflammatory model. Expression level of miR-155 was detected by Real-Time PCR. BV2 cells after simulated by LPS were then transfected with miR-155 mimic and its negative controls. Cytokines release were measured by corresponding purchased ELISA kits, respectively. Then target protein expression of miR-155 were detected by western blotting assay. After miRNA over expression transfections, expressions of inflammation-related factors, SOCS-1 and SAMD in BV2 cells after activation were measured by Western blot assay. Results showed that in BV2 cells after simulated by LPS, miR-155 was upregulated. The elevated miR-155 expression enhanced the inflammatory cytokine release. miR-155 directly target and negatively regulated SOCS-1 and SMAD-1 expression. Over expression of SOCS-1 and SMAD reduced inflammatory action that was enhanced by miR-155 mimic transfection. miR-155 was positively related with activation of NF-Ï°B signal pathways via SOCS-1 and SMAD. In conclusion, GuaLou GuiZhi Decoction (GLGZD) might exert its anti-inflammatory action by inhibiting the expression of miR-155, indicating that miR-155 may be used as a treatment target in clinical treatment with GuaLou GuiZhi Decoction (GLGZD) in ischemic brain.


Asunto(s)
Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Lipopolisacáridos/farmacología , MicroARNs/fisiología , Microglía/efectos de los fármacos , Animales , Isquemia Encefálica/tratamiento farmacológico , Células Cultivadas , Citocinas/biosíntesis , Ratones , MicroARNs/antagonistas & inhibidores , Microglía/fisiología , Proteína Smad1/antagonistas & inhibidores , Proteína 1 Supresora de la Señalización de Citocinas/antagonistas & inhibidores
10.
Biochem Biophys Res Commun ; 498(1): 246-253, 2018 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-29353042

RESUMEN

Presently, developing effective anti-colon cancer drugs still remains to be important. Ginkgolic acids (GA), as a botanical drug extracted from the seed coat of Ginkgo biloba L., possess various bioactive properties. Our findings, for the first time, indicated that GA suppressed colon cancer cell proliferation, migration and invasion. GA led to cell death through G0/G1 phase arrest. In addition, apoptosis was significantly induced by GA treatment. The intrinsic apoptosis pathway was included, proved by the release of cytochrome c (Cyto-c) from the mitochondria into the cytosol. GA-induced autophagy was supported by the dose-dependent increase of LC3BII, autophagy-related gene-5 (ATG-5) and Beclin-1. Notably, silencing ATG-5 further reduced the cell viability and enhanced apoptosis in GA-treated colon cancer cells, indicating that GA-induced apoptosis rather than autophagy contributes to colon cancer cell death. And mammalian target of rapamycin complex 1 (mTORC1) was dose-dependently reduced by GA, evidenced by the reduction of p-mTOR, p-p70 ribosomal S6 kinase (p70s6k) and p-pras40. Moreover, GA markedly resulted in reactive oxygen species (ROS) generation, along with increased H2O2 and O2-. However, blocking ROS generation using its scavenger, NAC, significantly recovered GA-induced cells death, supported by the increase of cell viability, and the decrease of apoptosis. The expressions of autophagy- and cell cycle arrest-related molecules, as well as mTORC1 were also reversed by N-acetyl-l-cysteine (NAC) in GA-treated cells. In vivo, GA reduced tumor growth without toxicity to animals. In conclusion, our study illustrated that GA caused G0/G1 phase arrest and triggered intrinsic apoptosis and autophagy modulated by ROS generation in human colon cancer, elucidating that GA might be considered as a potential agent for colon cancer therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias del Colon/patología , Especies Reactivas de Oxígeno/metabolismo , Salicilatos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Salicilatos/química
11.
Scott Med J ; 61(3): 149-154, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26610794

RESUMEN

This study aims to determine therapeutic effect of hemoperfusion on patients with acute toxic encephalopathy induced by silkworm chrysalis ingestion. Three patients who developed toxic encephalopathy after chrysalis ingestion were analysed. Two patients lost their consciousness, while two patients had typical extrapyramidal tremor symptoms. Further neurological examination revealed various degrees of muscle strength impairment in these patients. All of them received treatments of omeprazole (40 mg/day), furosemide (one dose of 20 mg), vitamin C (2.0 g/day), calcium gluconate (2.0 g/day) and rehydration with glucose and sodium chloride (1500 ml/day). In addition, they received hemoperfusion treatment for 1.5 h. All patients recovered well after hemoperfusion. Two patients with loss of consciousness significantly recovered at 45 min and 65 min after hemoperfusion, respectively. All tremor symptoms were completely resolved in these patients at 30 min, 50 min, and 70 min following treatment, respectively. After the hemoperfusion treatment, encephalopathy symptoms of two patients had completely disappeared. All patients were followed up for one month and did not report any abnormalities. Our study indicates that hemoperfusion could be a useful and efficient treatment strategy for patients with acute encephalopathy after silkworm chrysalis ingestion. Larger clinical trials with longer follow-up are warranted to confirm the clinical benefit of hemoperfusion.


Asunto(s)
Bombyx , Diuréticos/uso terapéutico , Enfermedades Transmitidas por los Alimentos/complicaciones , Furosemida/uso terapéutico , Hemoperfusión/métodos , Síndromes de Neurotoxicidad/etiología , Omeprazol/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto , Anciano , Animales , Gluconato de Calcio/uso terapéutico , Ingestión de Alimentos , Femenino , Fluidoterapia/métodos , Humanos , Masculino , Persona de Mediana Edad , Síndromes de Neurotoxicidad/terapia , Pupa/ultraestructura , Resultado del Tratamiento
12.
Food Chem ; 443: 138501, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38295565

RESUMEN

In this study, a dual-mode colorimetric/CL nanosensor was developed for glyphosate detection based on the specific inhibition of Fe3O4@Cu peroxidase-like activity. Synthesized Fe3O4@Cu exhibited high levels of peroxidase-like activity that triggered the oxidation of luminol/3,3',5,5'-tetramethyl benzidine dihydrochloride (TMB) to excited-state 3-aminophthalic acid/blue oxTMB, thereby delivering a CL signal/visible colorimetric signal, however, the presence of glyphosate inhibited this activity, resulting in a decrease in signal strength. In-depth investigation revealed that this inhibitory mechanism occurs via two pathways: one in which glyphosate chelates with Fe(III)/Cu(II) and occupy the catalytical active sites of Fe3O4@Cu, thereby decreasing the generation of OH, and another in which glyphosate competes with TMB to consume generated OH, thus reducing the oxidation of TMB. This mechanism formed the basis of our novel dual-mode colorimetric/CL glyphosate nanosensor, which achieved limits of detection (LODs) of 0.086 µg/mL and 0.019 µg/mL in tests, thus demonstrating its significant potential for on-site glyphosate monitoring.


Asunto(s)
Compuestos Férricos , Glifosato , Compuestos Férricos/química , Colorimetría/métodos , Oxidación-Reducción , Peroxidasas , Peróxido de Hidrógeno , Peroxidasa/metabolismo
13.
Front Oncol ; 14: 1390824, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38800384

RESUMEN

Previous studies indicated that adipose tissue significantly influences cancer invasion and lymphatic metastasis. However, the impact of neck adipose tissue (NAT) on lymph node metastasis associated with head and neck cancer remains ambiguous. Here, we systematically assess the classification and measurement criteria of NAT and evaluate the association of adipose tissue and cancer-associated adipocytes with head and neck cancer. We delve into the potential mechanisms by which NAT facilitate cervical lymph node metastasis in head and neck cancer, particularly through the secretion of adipokines such as leptin, adiponectin, and Interleukin-6. Our aim is to elucidate the role of NAT in the progression and metastasis of head and neck cancer, offering new insights into prevention and treatment.

14.
Front Genet ; 15: 1364476, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818043

RESUMEN

Introduction: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disease caused by abnormalities in motile cilia. In this case report, we first analyzed the clinical and genetic data of a proband who was suspected of having PCD on the basis of her clinical and radiological findings. Methods: Whole-exome sequencing was performed, and a variant in the RSPH4A gene was identified in the proband. Sanger sequencing was used for validation of RSPH4A variants in the proband, her sister, her daughter and her parents. Finally, the phenotypic features of the patient were analyzed, and the current literature was reviewed to better understand the gene variants in PCD related to hearing loss and the clinical manifestations of the RSPH4A variant in PCD. Results: The chief clinical symptoms of this proband included gradual mixed hearing loss, otitis media, anosmia, sinusitis, recurrent cough and infertility. Her DNA sequencing revealed a novel homozygous T to C transition at position 1321 within exon 3 of RSPH4A according to genetic testing results. This variant had never been reported before. The homozygous variant resulted in an amino acid substitution of tryptophan by arginine at position 441 (p.Trp441Arg). The same variant was also found in the proband's sister, and a heterozygous pathogenic variant was identified among immediate family members, including the proband's daughter and parents. Discussion: A literature review showed that 16 pathogenic variants in RSPH4A have been reported. Hearing loss had only been observed in patients with the RSPH4A (c.921+3_6delAAGT) splice site mutation, and the specific type of hearing loss was not described.

15.
Aging Cell ; 23(4): e14091, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38267829

RESUMEN

The pathogenesis of age-related hearing loss (ARHL) remains unclear. OPA1 is the sole fusion protein currently known to be situated in the inner mitochondrial membrane, which is pivotal for maintaining normal mitochondrial function. While it has already been demonstrated that mutations in OPA1 may lead to hereditary deafness, its involvement in the occurrence and development of ARHL has not been previously explored. In our study, we constructed D-gal-induced senescent HEI-OC1 cells and the cochlea of C57BL/6J mice with a mutated SUMOylation site of SIRT3 using CRISPR/Cas9 technology. We found enhanced L-OPA1 processing mediated by activated OMA1, and increased OPA1 acetylation resulting from reductions in SIRT3 levels in senescent HEI-OC1 cells. Consequently, the fusion function of OPA1 was inhibited, leading to mitochondrial fission and pyroptosis in hair cells, ultimately exacerbating the aging process of hair cells. Our results suggest that the dysregulation of mitochondrial dynamics in cochlear hair cells in aged mice can be ameliorated by activating the SIRT3/OPA1 signaling. This has the potential to alleviate the senescence of cochlear hair cells and reduce hearing loss in mice. Our study highlights the significant roles played by the quantities of long and short chains and the acetylation activity of OPA1 in the occurrence and development of ARHL. This finding offers new perspectives and potential targets for the prevention and treatment of ARHL.


Asunto(s)
Presbiacusia , Sirtuina 3 , Animales , Ratones , Acetilación , Ratones Endogámicos C57BL , Dinámicas Mitocondriales/genética , Sirtuina 3/genética , Sirtuina 3/metabolismo
16.
Plasmid ; 70(3): 314-20, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23928042

RESUMEN

Newcastle disease virus (NDV) can cause serious diseases and substantial economic losses to the poultry industry. To gain a better understanding of NDV pathogenesis, several reverse genetics systems for different NDV strains have been established. However, the construction of infectious cDNA clone by conventional restriction digestion/ligation cloning methods is a time-consuming process and has many drawbacks by its nature. To address the problems, we employed a novel and robust ligation-independent cloning (LIC) method for efficient assembly of multiple DNA fragments. Using this method, we successfully generated a NDV minigenome construct within three weeks by assembling RT-PCR products of the VG/GA strain genomic termini and a cDNA coding for the green fluorescence protein (GFP), as a reporter, into a modified pBluescript vector. Co-transfection of the NDV minigenome with three supporting plasmids expressing the N, P, and L proteins into MVA-T7 infected HEp-2 cells and followed by infection with NDV VG/GA resulted in the minigenome replication, transcription, and packaging as evidenced by the reporter gene GFP expression. These results suggest that this LIC approach is a powerful tool for all sequence-independent DNA cloning and multi-DNA fragment assembly, which has a potential application for rapid development of gene therapy and recombinant vaccines.


Asunto(s)
Cromosomas Artificiales , Clonación Molecular/métodos , Genoma Viral , Virus de la Enfermedad de Newcastle/genética , ARN Viral/genética , Línea Celular Tumoral , ADN Complementario/química , ADN Complementario/genética , Células Epiteliales/virología , Genes Reporteros , Ingeniería Genética/métodos , Vectores Genéticos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Virus de la Enfermedad de Newcastle/química , Plásmidos , ARN Viral/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Virus Genes ; 47(1): 27-33, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23549884

RESUMEN

The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) plays an important role in virus pathogenicity and tissue tropism. Sequence analysis revealed that the HN gene of many asymptomatic enteric NDV strains encodes a larger open reading frame (616 amino acids, aa) with additional 39 aa at its C-terminus when compared with that (577 aa) of respirotropic NDV strains. Therefore, it has been suspected that the HN C-terminal extension may contribute to the enteric tropism. In the present study, we generated a NDV respirotropic strain LaSota-based recombinant virus with a HN C-terminal extension of 39 aa derived from an enterotropic NDV strain using reverse genetics technology. The biological characterization of the recombinant virus, rLS-HN-ex, showed that the HN C-terminal extension slightly attenuated the virus pathogenicity in embryonated eggs and in day-old chicks when compared to the parental LaSota virus. However, the HN C-terminal extension did not alter virus tissue tropism. In infected chickens, the recombinant virus was detected and re-isolated from the tracheal tissue, but not from the intestinal tissue, exhibiting a similar respirotropic tissue preference as its parental LaSota strain. These results demonstrated that the HN protein C-terminal extension of NDV is not the determinant of the virus enteric tropism.


Asunto(s)
Proteína HN/química , Proteína HN/metabolismo , Intestinos/virología , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/fisiología , Enfermedades de las Aves de Corral/virología , Tropismo Viral , Secuencia de Aminoácidos , Animales , Pollos , Proteína HN/genética , Datos de Secuencia Molecular , Virus de la Enfermedad de Newcastle/química , Virus de la Enfermedad de Newcastle/genética , Especificidad de Órganos , Estructura Terciaria de Proteína , Tráquea/virología
18.
Anal Chim Acta ; 1276: 341618, 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37573108

RESUMEN

Due to their superparamagnetism and enzyme-like activity, iron oxide (Fe3O4) nanozymes can be readily used for sample pretreatment and the generation of detection signals, and have, thus, attracted much attention in the field of bioanalysis and diagnosis. However, the low catalytic activity of Fe3O4 nanozymes does reduce the sensitivity of Fe3O4-based methods, limiting their application. In this study, Fe3O4@Cu@poly(pyrrole-2-carboxylic acid) yolk-shell nanozymes (Fe3O4@Cu@PCPy YSNs) were synthesized using a facile approach and selective chemical etching technology. Compared with Fe3O4 nanozymes, the Fe3O4@Cu@PCPy YSNs demonstrated a three-fold increase in the peroxidase-like activity, good dispersity and strong superparamagnetism. In addition, the flower-shaped structure of aptamer-complementary strand (Apt-CS) conjugates was designed on the surface of the Fe3O4@Cu@PCPy YSNs, which effectively inhibited their peroxidase-like activity by creating a physical barrier that hindered the access of substrates to the center of the Fe3O4@Cu@PCPy YSNs. Based on this principle, a robust and facile colorimetric aptasensor was developed for detecting Salmonella Typhimurium. The flower-shaped Apt-CS were dissociated in the presence of S. Typhimurium, promoting the recovery of Fe3O4@Cu@PCPy YSN catalytic activity. Under optimized conditions, this proposed aptasensor successfully detected S. Typhimurium in a linear range of 3 to 3 × 106 CFU/mL, achieving a detection limit of 1 CFU/mL. Finally, the feasibility of this novel aptasensor was further validated by three actual samples, with recoveries of between 84.3% and 102%, thereby demonstrating the huge potential of the proposed aptasensor for detecting S. Typhimurium in foods.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Salmonella typhimurium , Colorimetría , Aptámeros de Nucleótidos/química , Peroxidasas , Límite de Detección , Técnicas Biosensibles/métodos
19.
Adv Sci (Weinh) ; 10(8): e2205040, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36658728

RESUMEN

Despite the simplified fabrication process and desirable microstructural stability, the limited charge transport properties of block copolymers and double-cable conjugated polymers hinder the overall performance of single-component photovoltaic devices. Based on the key distinction in the donor (D)-acceptor (A) bonding patterns between single-component and bulk heterojunction (BHJ) devices, rationalizing the difference between the transport mechanisms is crucial to understanding the structure-property correlation. Herein, the barrier formed between the D-A covalent bond that hinders electron transport in a series of single-component photovoltaic devices is investigated. The electron transport in block copolymer-based devices is strongly dependent on the electric field. However, these devices demonstrate exceptional advantages with respect to the charge transport properties, involving high stability to compositional variations, improved film uniformity, and device reproducibility. This work not only illustrates the specific charge transport behavior in block copolymer-based devices but also clarifies the enormous commercial viability of large-area single-component organic solar cells (SCOSCs).

20.
Front Cell Neurosci ; 17: 1308028, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38239289

RESUMEN

Cholesterol is the most abundant sterol molecule in mammalian cells, which not only constitutes the cell membrane but also plays essential roles in the synthesis of important hormones, synapse formation, and cell signal transduction. The effect of hypercholesterolemia on hearing has been studied extensively, and multiple studies have demonstrated that hypercholesterolemia is a risk factor for hearing loss. However, the impact of cholesterol homeostasis within auditory cells on peripheral auditory development and maintenance has not been evaluated in detail. Mutations in certain cholesterol metabolism-related genes, such as NPC1, SERAC1, DHCR7, and OSBPL2, as well as derivatives of cholesterol metabolism-related ototoxic drugs, such as ß-cyclodextrin, can lead to disruptions of cholesterol homeostasis within auditory cells, resulting in hearing loss. This article aims to review the impact of cholesterol homeostasis within auditory cells on the peripheral auditory function from the following two perspectives: (1) changes in cholesterol homeostasis regulatory genes in various hearing loss models; (2) mechanisms underlying the effects of some drugs that have a therapeutic effect on hearing loss via regulating cholesterol homeostasis. This article aims to summarize and analyze the impact of disruption of cellular cholesterol homeostasis within auditory cells on hearing, in order to provide evidence regarding the underlying mechanisms.

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