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1.
J Virol ; 98(7): e0046724, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38864621

RESUMEN

Acinetobacter baumannii, an opportunistic pathogen, poses a significant threat in intensive care units, leading to severe nosocomial infections. The rise of multi-drug-resistant strains, particularly carbapenem-resistant A. baumannii, has created formidable challenges for effective treatment. Given the prolonged development cycle and high costs associated with antibiotics, phages have garnered clinical attention as an alternative for combating infections caused by drug-resistant bacteria. However, the utilization of phage therapy encounters notable challenges, including the narrow host spectrum, where each phage targets a limited subset of bacteria, increasing the risk of phage resistance development. Additionally, uncertainties in immune system dynamics during treatment hinder tailoring symptomatic interventions based on patient-specific states. In this study, we isolated two A. baumannii phages from wastewater and conducted a comprehensive assessment of their potential applications. This evaluation included sequencing analysis, genome classification, pH and temperature stability assessments, and in vitro bacterial inhibition assays. Further investigations involved analyzing histological and cytokine alterations in rats undergoing phage cocktail treatment for pneumonia. The therapeutic efficacy of the phages was validated, and transcriptomic studies of rat lung tissue during phage treatment revealed crucial changes in the immune system. The findings from our study underscore the potential of phages for future development as a treatment strategy and offer compelling evidence regarding immune system dynamics throughout the treatment process.IMPORTANCEDue to the growing problem of multi-drug-resistant bacteria, the use of phages is being considered as an alternative to antibiotics, and the genetic safety and application stability of phages determine the potential of phage application. The absence of drug resistance genes and virulence genes in the phage genome can ensure the safety of phage application, and the fact that phage can remain active in a wide range of temperatures and pH is also necessary for application. In addition, the effect evaluation of preclinical studies is especially important for clinical application. By simulating the immune response situation during the treatment process through mammalian models, the changes in animal immunity can be observed, and the effect of phage therapy can be further evaluated. Our study provides compelling evidence that phages hold promise for further development as therapeutic agents for Acinetobacter baumannii infections.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Carbapenémicos , Modelos Animales de Enfermedad , Terapia de Fagos , Acinetobacter baumannii/virología , Acinetobacter baumannii/efectos de los fármacos , Animales , Infecciones por Acinetobacter/terapia , Infecciones por Acinetobacter/microbiología , Ratas , Terapia de Fagos/métodos , Carbapenémicos/farmacología , Bacteriófagos/fisiología , Bacteriófagos/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Masculino , Genoma Viral , Aguas Residuales , Neumonía/terapia , Neumonía/microbiología , Neumonía/virología
2.
Appl Microbiol Biotechnol ; 108(1): 428, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066795

RESUMEN

Acinetobacter baumannii, which is resistant to multiple drugs, is an opportunistic pathogen responsible for severe nosocomial infections. With no antibiotics available, phages have obtained clinical attention. However, since immunocompromised patients are often susceptible to infection, the appropriate timing of administration is particularly important. During this research, we obtained a lytic phage vB_AbaM_P1 that specifically targets A. baumannii. We then assessed its potential as a prophylactic treatment for lung infections caused by clinical strains. The virus experiences a period of inactivity lasting 30 min and produces approximately 788 particles during an outbreak. Transmission electron microscopy shows that vB_AbaM_P1 was similar to the Saclayvirus. Based on the analysis of high-throughput sequencing and bioinformatics, vB_AbaM_P1 consists of 107537 bases with a G + C content of 37.68%. It contains a total of 177 open reading frames and 14 tRNAs. No antibiotic genes were detected. In vivo experiments, using a cyclophosphamide-induced neutrophil deficiency model, tested the protective effect of phage on neutrophil-deficient rats by prophylactic application of phage. The use of phages resulted in a decrease in rat mortality caused by A. baumannii and a reduction in the bacterial burden in the lungs. Histologic examination of lung tissue revealed a decrease in the presence of immune cells. The presence of phage vB_AbaM_P1 had a notable impact on preventing A. baumannii infection, as evidenced by the decrease in oxidative stress in lung tissue and cytokine levels in serum. Our research offers more robust evidence for the early utilization of bacteriophages to mitigate A. baumannii infection. KEY POINTS: •A novel Saclayvirus phage infecting A. baumannii was isolated from sewage. •The whole genome was determined, analyzed, and compared to other phages. •Assaying the effect of phage in preventing infection in neutrophil-deficient models.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Genoma Viral , Acinetobacter baumannii/virología , Acinetobacter baumannii/genética , Animales , Infecciones por Acinetobacter/prevención & control , Infecciones por Acinetobacter/microbiología , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Bacteriófagos/fisiología , Ratas , Terapia de Fagos/métodos , Composición de Base , Modelos Animales de Enfermedad , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Pulmón/virología , Pulmón/microbiología , Neumonía/prevención & control , Neumonía/microbiología , Neumonía/virología , Masculino
3.
BMC Womens Health ; 24(1): 527, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304877

RESUMEN

BACKGROUND: Perivascular epithelioid cell tumours (PEComas) are soft tissue tumours. These neoplasms belong to the family of mesenchymal tumours, which include angiomyolipomas, clear-cell sugar tumours of the lung, and PEComas not otherwise specified (NOS). The probability of a perivascular epithelioid cell tumour (PEComa) occurring in the uterus is low, and the incidence, diagnosis, treatment, and outcomes of such tumours are still unclear. CASE PRESENTATION: A 51-year-old woman presented a 4-year history of natural menopause. An intrauterine mass was detected via ultrasound examination; the mass showed a tendency to increase but caused no symptoms. The levels of tumour markers were within the normal range. Pathological analysis of the curettage revealed perivascular epithelioid differentiation of the endometrial tumour. Consequently, a laparoscopic total hysterectomy with bilateral adnexectomy was performed. No distant metastasis was detected via whole-body positron emission computed tomography (PETCT) after the operation. Fluorescence in situ hybridization (FISH) revealed no TFE3 gene rearrangement. Next-generation sequencing of bone and soft tissue revealed negative TSC1/2 and TP53 expression. No recurrence or metastasis was observed during the 18-month follow-up period. CONCLUSION: PEComa of the gynecologic tract is a rare and challenging entity. Diffuse HMB-45 expression, TSC alterations and TFE3 rearrangement are characteristic of uterine PEComas. Surgical resection is the first choice. Genetic testing is helpful for determining the nature of the mass and for choosing targeted therapy. Further research is needed to establish treatment protocols.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Reordenamiento Génico , Neoplasias de Células Epitelioides Perivasculares , Neoplasias Uterinas , Humanos , Femenino , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/cirugía , Neoplasias de Células Epitelioides Perivasculares/patología , Persona de Mediana Edad , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/diagnóstico , Reordenamiento Génico/genética , Histerectomía/métodos
4.
Environ Geochem Health ; 46(8): 270, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954122

RESUMEN

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.


Asunto(s)
Radioisótopos de Cesio , Minería , Contaminantes Radiactivos del Suelo , Medición de Riesgo , China , Contaminantes Radiactivos del Suelo/análisis , Radioisótopos de Cesio/análisis , Humanos , Radioisótopos de Estroncio/análisis , Cesio/análisis , Ciudades , Suelo/química , Método de Montecarlo , Monitoreo de Radiación
5.
Cancer Sci ; 114(4): 1396-1409, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36562402

RESUMEN

Emerging evidence has suggested that circular RNAs (circRNAs) have vital functions during the initiation and progression of various diseases. However, circRNA potential mechanisms in colorectal cancer (CRC) are largely unknown. Here, we sought to investigate the role and underlying regulatory mechanism of circ0104103 in CRC. circ0104103 was validated by quantitative RT-PCR (qRT-PCR) and Sanger sequencing. Gain- and loss-of-function assays in cell lines and mouse xenograft models were utilized to investigate the effects of circ0104103 in CRC. RNA pull-down assays, RNA immunoprecipitation assays, bioinformatics analyses, RNA FISH, and luciferase reporter assays were used to elucidate the potential mechanism of circ0104103 in CRC. We identified circ0104103, which is strongly downregulated in CRC tissues and cell lines. Functional studies revealed that circ0104103 inhibited CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, circ0104103 binds to HuR, a functional RNA-binding protein commonly expressed in CRC. HuR binds to the 3'UTR of LACTB mRNA to facilitate stabilization and increase its expression. Moreover, circ0104103 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR-373-5p to increase LACTB expression, resulting in inhibiting the occurrence and progression of CRC. Taken together, our study revealed that circ0104103 acts as a tumor suppressor and may be a novel biomarker and therapeutic target in CRC.


Asunto(s)
Neoplasias Colorrectales , Proteína 1 Similar a ELAV , MicroARNs , ARN Circular , Animales , Humanos , Ratones , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de la Membrana/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Mitocondriales/metabolismo , Interferencia de ARN , ARN Circular/genética , Proteína 1 Similar a ELAV/genética , Proteína 1 Similar a ELAV/metabolismo
6.
Opt Express ; 31(16): 26301-26313, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710493

RESUMEN

We have developed a simple time-bin phase encoding quantum key distribution system, using the optical injection locking technique. This setup incorporates both the merits of simplicity and stability in encoding, and immunity to channel disturbance. We have demonstrated the field implementation of quantum key distribution over long-distance deployed aerial fiber automatically. During the 70-day field test, we achieved approximately a 1.0 kbps secure key rate with stable performance. Our work takes an important step toward widespread implementation of QKD systems in diverse and complex real-life scenarios.

7.
Opt Express ; 31(16): 26335-26343, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710496

RESUMEN

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

8.
Fam Pract ; 40(1): 105-112, 2023 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-35809033

RESUMEN

BACKGROUND: As one of the 3 strategic measures for disease prevention and control in the 21st century identified by WHO, patient education is the most effective measure to change people's behaviour and lifestyle. However, there are many problems with patient education in general practice in China. Because there is no suitable and uniform mode of patient education for the busy and crowded Chinese general practice. Therefore, it is necessary to establish an appropriate personalized patient education model. METHODS: There were 3 rounds of consultation of the Delphi method. Each round of consultation is adjusted, modified, or deleted based on the previous round according to the degree of concentration and coordination of expert opinions. Thus form the index system of personalized patient education model. Using Cronbach α to conduct an internal consistency test for the index system. RESULTS: Twenty-three participants participated in the study. The effective recovery rate of consultation was 100%. In the third round of consultation, the variation importance coefficient was 0-0.25, the variation operability coefficient was 0.07-0.26. Kendall's W of importance and operability score was significant (Kendall's W = 0.186; P < 0.01). The chi-square test result of importance is (X2 = 232.744) and operability is (X2 = 246.156). The Cronbach α was 0.974. EFA (exploratory factor analysis) indicates the model has good construct validity. CONCLUSIONS: The CAPDCA personalized patient education model was preliminarily constructed in this study. Specifically, 6 first-level indicators including collection (C), assessment (A), plan (P), do (D), check (C), aggrandizement (A), 24 second-level indicators, and 34 third-level indicators. That forms the cyclic personalized patient education paradigm which has reasonable structure and high feasibility.


Asunto(s)
Medicina General , Educación del Paciente como Asunto , Humanos , Técnica Delphi , Estilo de Vida , Derivación y Consulta , China , Encuestas y Cuestionarios
9.
BMC Musculoskelet Disord ; 24(1): 24, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36631884

RESUMEN

PURPOSE: To investigate the clinical efficacy of transforaminal endoscopic discectomy (TED) in treating recurrent lumbar disc herniation. METHODS: Clinical datal of 31 patients who were hospitalized in the Department of Pain Management, First Affiliated Hospital of Nanchang University, between 2015 and 2018 due to recurrent lumbar disc herniation were collected and analyzed retrospectively. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were used to assess alterations of patients' leg pain intensity and nerve function, respectively. The Modified MacNab criteria were used to evaluate patients' excellent and good rates. RESULTS: Compared to clinical data before surgery, there was a significant reduction in VAS scores (P < 0.01) along with a significant improvement in JOA scores (P < 0.01) at 2 years after revision surgery. The patients' excellent and good rates were 83.9% at the 2 years after surgery. CONCLUSION: The TED is safe and effective in the long term and is applicable to the treatment of recurrent lumbar disc herniation.


Asunto(s)
Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Estudios Retrospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Discectomía/efectos adversos , Endoscopía , Resultado del Tratamiento
10.
PLoS Genet ; 16(2): e1008641, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32059012

RESUMEN

Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10-03), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10-02), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10-03). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10-48). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10-125). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1, PCAT1 and PCAT10/CTBP1-AS, were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes.


Asunto(s)
Biomarcadores de Tumor/genética , Negro o Afroamericano/genética , Disparidades en el Estado de Salud , Neoplasias de la Próstata/genética , Población Blanca/genética , Biomarcadores de Tumor/metabolismo , Secuenciación de Inmunoprecipitación de Cromatina , Estudios de Cohortes , Regulación Neoplásica de la Expresión Génica , Genoma Humano/genética , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mutación , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Fosfohidrolasa PTEN/genética , Neoplasias de la Próstata/epidemiología , ARN Largo no Codificante/metabolismo , RNA-Seq , Receptores Androgénicos/genética , Proteínas Represoras/genética , Transcriptoma/genética
11.
J Environ Sci (China) ; 128: 12-25, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36801028

RESUMEN

Comprehensive studies of the effects of various physical and chemical variables (including heavy metals), antibiotics, and microorganisms in the environment on antibiotic resistance genes are rare. We collected sediment samples from the Shatian Lake aquaculture area and surrounding lakes and rivers located in Shanghai, China. The spatial distribution of sediment ARGs was assessed by metagenomic analysis that revealed 26 ARG types (510 subtypes), dominated by Multidrug, ß-lactam, Aminoglycoside, Glycopeptides, Fluoroquinolone, and Tetracyline. Redundancy discriminant analysis indicated that antibiotics (SAs and MLs) in the aqueous environment and sediment along with water TN and TP were the key variables affecting the abundance distribution of total ARGs. However, the main environmental drivers and key influences differed among the different ARGs. For total ARGs, the environmental subtypes affecting their structural composition and distribution characteristics were mainly antibiotic residues. Procrustes analysis showed a significant correlation between ARGs and microbial communities in the sediment in the survey area. Network analysis revealed that most of the target ARGs were significantly and positively correlated with microorganisms, and a small number of ARGs (e.g., rpoB, mdtC, and efpA) were highly significantly and positively correlated with microorganisms (e.g., Knoellia, Tetrasphaera, and Gemmatirosa). Potential hosts for the major ARGs included Actinobacteria, Proteobacteria, and Gemmatimonadetes. Our study provides new insight and a comprehensive assessment of the distribution and abundance of ARGs and the drivers of ARG occurrence and transmission.


Asunto(s)
Antibacterianos , Genes Bacterianos , Antibacterianos/farmacología , China , Bacterias/genética , Farmacorresistencia Microbiana/genética
12.
Thorac Cardiovasc Surg ; 70(5): 413-421, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-33477177

RESUMEN

OBJECTIVE: Paravertebral block (PVB) and thoracic epidural analgesia (TEA) are commonly used for postthoracotomy pain management. The purpose of this research is to evaluate the effects of TEA versus PVB for postthoracotomy pain relief. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library (last performed on August 2020) to identify randomized controlled trials comparing PVB and TEA for thoracotomy. The rest and dynamic visual analog scale (VAS) scores, rescue analgesic consumption, the incidences of side effects were pooled. RESULTS: Sixteen trials involving 1,000 patients were included in this meta-analysis. The pooled results showed that the rest and dynamic VAS at 12, 24, and rest VAS at 48 hours were similar between PVB and TEA groups. The rescue analgesic consumption (weighted mean differences: 3.81; 95% confidence interval [CI]: 0.982-6.638, p < 0.01) and the incidence of rescue analgesia (relative risk [RR]: 1.963; 95% CI: 1.336-2.884, p < 0.01) were less in TEA group. However, the incidence of hypotension (RR: 0.228; 95% CI: 0.137-0.380, p < 0.001), urinary retention (RR: 0.392; 95% CI: 0.198-0.776, p < 0.01), and vomiting (RR: 0.665; 95% CI: 0.451-0.981, p < 0.05) was less in PVB group. CONCLUSION: For thoracotomy, PVB may provide no superior analgesia compared with TEA but PVB can reduce side effects. Thus, individualized treatment is recommended. Further study is still necessary to determine which concentration of local anesthetics can be used for PVB and can provide equal analgesic efficiency to TEA.


Asunto(s)
Analgesia Epidural , Bloqueo Nervioso , Dolor Postoperatorio , Humanos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Toracotomía/efectos adversos , Resultado del Tratamiento
13.
J Cell Physiol ; 235(5): 4928-4940, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31674013

RESUMEN

MicroRNA-142-3p (miR-142-3p) was previously investigated in various cancers, whereas, it's role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumor-suppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment.


Asunto(s)
Neoplasias de la Mama/enzimología , MicroARNs/metabolismo , Quinasas p21 Activadas/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Animales , Apoptosis , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Movimiento Celular , Proliferación Celular , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Neovascularización Patológica , Fosforilación , Transducción de Señal , Quinasas p21 Activadas/genética , Proteína de Unión al GTP rac1/genética
14.
Mol Cancer ; 19(1): 106, 2020 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-32552762

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide, and its main cause of death is distant metastasis. Methyltransferase-like 14(METTL14), a major RNA N6-adenosine methyltransferase, is involved in tumor progression via regulating RNA function. The goal of the study is to uncover the biological function and molecular mechanism of METTL14 in CRC. METHODS: Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) assays were employed to detect METTL14 and SOX4 in CRC cell lines and tissues. The biological functions of METTL14 were demonstrated using in vitro and in vivo experiments. Chromatin immunoprecipitation (ChIP), Transcrptomic RNA sequencing (RNA-Seq), m6A-RNA immunoprecipitation sequencing (MeRIP-Seq), RNA immunoprecipitation and luciferase reporter assays were used to explore the mechanism of METTL14 action. RESULTS: METTL14 expression was significantly downregulated in CRC and decreased METTL14 was associated with poor overall survival (OS). Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, lysine-specific histone demethylase 5C(KDM5C)-mediated demethylation of histone H3 lysine 4 tri-methylation(H3K4me3) in the promoter of METTL14 inhibited METTL14 transcription. Functionally, we verified that METTL14 inhibited CRC cells migration, invasion and metastasis through in vitro and in vivo assays, respectively. Furthermore, we identified SRY-related high-mobility-group box 4(SOX4) as a target of METTL14-mediated m6A modification. Knockdown of METTL14 markedly abolished SOX4 mRNA m6A modification and elevated SOX4 mRNA expression. We also revealed that METTL14-mediated SOX4 mRNA degradation relied on the YTHDF2-dependent pathway. Lastly, we demonstrated that METTL14 might inhibit CRC malignant process partly through SOX4-mediated EMT process and PI3K/Akt signals. CONCLUSIONS: Decreased METTL14 facilitates tumor metastasis in CRC, suggesting that METTL14 might be a potential prognostic biomarker and effective therapeutic target for CRC.


Asunto(s)
Adenosina/análogos & derivados , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/prevención & control , Regulación Neoplásica de la Expresión Génica , Metiltransferasas/metabolismo , Factores de Transcripción SOXC/genética , Adenosina/química , Animales , Apoptosis , Biomarcadores de Tumor/genética , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Humanos , Metiltransferasas/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Pronóstico , Factores de Transcripción SOXC/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
15.
IUBMB Life ; 72(12): 2663-2671, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33141516

RESUMEN

Our previous study showed that silencing of lncRNA Gm14461 alleviated pain in a murine model of trigeminal neuralgia (TN), but the molecular mechanism remains not fully understood. Evidence indicates that astrocyte activation and autophagy are involved in the development of TN. Herein, this study aimed to elucidate whether the pain-relief effect of Gm14461 silencing in TN involved regulation of astrocyte activation and autophagy. A murine model of TN was induced by chronic constriction injury of the infraorbital nerve surgery. The mechanical withdrawal threshold (MWT) was measured to assess the analgesic effect of Gm14461 silencing. Mouse astrocytes were treated with lipopolysaccharide (LPS) as a cell model. Astrocyte activation was evaluated by glial fibrillary acidic protein (GFAP) immunofluorescence and western blot analysis of GFAP. Autophagy was evaluated by LC3 immunofluorescence and western blot analysis of autophagy-related proteins. The results showed that Gm14461 silencing increased MWT value in TN model mice. Meanwhile, Gm14461 silencing inhibited astrocyte activation and enhanced autophagy in both TN mice and LPS-treated astrocytes. The enhancement of autophagy by Gm14461 silencing involved the activation of the AMPK signaling and the suppression of the Akt/mTOR signaling. Collectively, the analgesic effect of Gm14461 silencing in TN was related to attenuation of astrocyte activation via enhancement of autophagy.


Asunto(s)
Astrocitos/inmunología , Modelos Animales de Enfermedad , Hiperalgesia/prevención & control , Dolor/prevención & control , ARN Largo no Codificante/antagonistas & inhibidores , Neuralgia del Trigémino/patología , Animales , Astrocitos/metabolismo , Autofagia , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Hiperalgesia/patología , Ratones , Ratones Endogámicos C57BL , Dolor/etiología , Dolor/metabolismo , Dolor/patología , ARN Largo no Codificante/genética , Transducción de Señal
16.
IUBMB Life ; 72(7): 1393-1403, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32107843

RESUMEN

Metastasis is responsible for 90% of colorectal cancer (CRC)-related deaths. In the present study, we identified a novel key regulator of CRC metastasis, leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3), which was significantly decreased in CRC tissues and cell lines. Downregulation of LRIG3 was attributed to copy number loss and promoter hypermethylation. Low LRIG3 expression was positively correlated with metastatic clinical features and shorter survival time. Functional experiments showed that knockout of LRIG3 markedly enhanced CRC cell migration and invasion ability, whereas reintroduction of LRIG3 exerted the opposite effects. Regarding the mechanism, LRIG3 could facilitate the binding of DUSP6 to ERK1/2, resulting in the dephosphorylation of ERK1/2 and subsequently downregulation of slug, an epithelial-to-mesenchymal transition trigger, thereby constraining CRC cell motility. Importantly, LRIG3 expression was strongly negatively correlated with slug or p-ERK1/2 expression in CRC tissues. Collectively, our data suggest that LRIG3 is a novel suppressor of CRC metastasis, reactivation of LRIG3 may be a promising therapeutic approach for metastatic CRC patients.


Asunto(s)
Movimiento Celular , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Anciano , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Masculino , Proteínas de la Membrana/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Fosforilación , Pronóstico , Transducción de Señal , Factores de Transcripción de la Familia Snail/genética , Tasa de Supervivencia , Células Tumorales Cultivadas
17.
Br J Neurosurg ; : 1-7, 2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33331186

RESUMEN

OBJECTIVE: To observe the surgical procedure and outcome of percutaneous endoscopic lumbar discectomy for L5/S1 lumbar disc herniation (LDH) by the interlaminar and transforaminal approach. METHODS: A total of 153 patients with L5/S1 LDH who were treated using percutaneous endoscopic transforaminal discectomy (PETD, n = 84) or percutaneous endoscopic interlaminar discectomy (PEID, n = 69) from January 2016 to January 2018 were enrolled in this retrospective study. The time of puncture, operation under the endoscope, total operation and number of fluoroscopy of the two groups were compared. All groups were followed up for two years by using the Oswestry disability index (ODI) and the Visual Analogue Scale (VAS). Additionally, the incidence of complications, reoperation and postoperative low back pain were compared between the two groups. RESULTS: There were no significant difference in general information between the two groups. Compared to the PEID group, the PETD group had a decreased operation time under the endoscope and an increased puncture time, total operation time, and the number of fluoroscopy (p < 0.05). The preoperative VAS and ODI scores of the PETD and PEID group were decreased at the last follow-up (p < 0.05). There were no difference in the preoperative or last follow-up VAS and ODI scores, as well as complications, reoperation between the two groups (p > 0.05). The incidence of postoperative low back pain in the PETD group was lower than that in the PEID group (p > 0.05). CONCLUSIONS: The two-year clinical outcome of PETD is equal to that of PEID for L5/S1 LDH. Compared to those with PETD, the puncture time, total operation time and radiation exposure are lower with PEID, but the incidence of postoperative low back pain is higher.

18.
Mol Cancer ; 18(1): 135, 2019 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-31492160

RESUMEN

BACKGROUND: Emerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we report a lncRNA, SATB2-AS1, which is specifically expressed in colorectal tissue and is significantly reduced in CRC. We systematically elucidated its functions and possible molecular mechanisms in CRC. METHODS: LncRNA expression in CRC was analyzed by RNA-sequencing and RNA microarrays. The expression level of SATB2-AS1 in tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). The functional role of SATB2-AS1 in CRC was investigated by a series of in vivo and in vitro assays. RNA pull-down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), chromatin isolation by RNA purification (ChIRP), Bisulfite Sequencing PCR (BSP) and bioinformatics analysis were utilized to explore the potential mechanisms of SATB2-AS1. RESULTS: SATB2-AS1 is specifically expressed in colorectal tissues and downregulated in CRC. Survival analysis indicates that decreased SATB2-AS1 expression is associated with poor survival. Functional experiments and bioinformatics analysis revealed that SATB2-AS1 inhibits CRC cell metastasis and regulates TH1-type chemokines expression and immune cell density in CRC. Mechanistically, SATB2-AS1 directly binds to WDR5 and GADD45A, cis-activating SATB2 (Special AT-rich binding protein 2) transcription via mediating histone H3 lysine 4 tri-methylation (H3K4me3) deposition and DNA demethylation of the promoter region of SATB2. CONCLUSIONS: This study reveals the functions of SATB2-AS1 in CRC tumorigenesis and progression, suggesting new biomarkers and therapeutic targets in CRC.


Asunto(s)
Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión a la Región de Fijación a la Matriz/genética , ARN sin Sentido , ARN Largo no Codificante , Factores de Transcripción/genética , Microambiente Tumoral/genética , Adulto , Anciano , Animales , Biomarcadores de Tumor , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/mortalidad , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Xenoinjertos , Histonas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Ratones , Persona de Mediana Edad , Estadificación de Neoplasias , Regiones Promotoras Genéticas , Interferencia de ARN , Microambiente Tumoral/inmunología
19.
Opt Lett ; 44(17): 4347-4350, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31465398

RESUMEN

We propose and experimentally demonstrate a proactive real-time interference avoidance scheme using SARSA reinforcement learning (RL) in a millimeter-wave over a fiber mobile fronthaul system. The RL consists of three core factors, including state, action, and reward. The state is defined as a discretized value from the center frequency, the left, right, and center sub-EVM of the signal. We use five actions to shift the signal frequency in the proposed scheme, which is -20, -10, 0, 10, and 20 MHz, for the RL agent to choose the action to avoid the dynamic interference. For the agent to learn from the experience, the reward is defined as the log value of BER difference between the past and the present state. The RL-based approach is an online learning algorithm, which can learn in real time based on environmental feedback. Besides, the agent can learn from past experience owing to the Q-value table, which makes it act intelligently when facing a similar situation again. We verify the capability of the proposed scheme under both fixed and dynamic interference scenarios. The agent demonstrates an efficient intelligent mechanism to avoid the interference, which provides a promising solution for proactive interference mitigation in the 5 G mobile fronthaul network.

20.
Mol Cancer ; 17(1): 141, 2018 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-30266084

RESUMEN

BACKGROUND: Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles during the initiation and progression of cancers. In this study, we report that the small nucleolar RNA host gene 1 (SNHG1) is involved in colorectal cancer progression. METHODS: We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer. The effects of SNHG1 on colorectal cancer were investigated through in vitro and in vivo assays (i.e., CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and western blot). The mechanism of SNHG1 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay. RESULTS: Our analysis revealed that SNHG1 was upregulated in human colorectal cancer tissues, and high SNHG1 expression was associated with reduced patient survival. We also found that high SNHG1 expression was partly induced by SP1. Moreover, SNHG1 knockdown significantly repressed colorectal cancer cells growth both in vitro and in vivo. Mechanistic investigations demonstrated that SNHG1 could directly interact with Polycomb Repressive Complex 2 (PRC2) and modulate the histone methylation of promoter of Kruppel like factor 2 (KLF2) and Cyclin dependent kinase inhibitor 2B (CDKN2B) in the nucleus. In the cytoplasm, SNHG1 acted as a sponge for miR-154-5p, reducing its ability to repress Cyclin D2 (CCND2) expression. CONCLUSIONS: Taken together, the results of our studies illuminate how SNHG1 formed a regulatory network to confer an oncogenic function in colorectal cancer and suggest that SNHG1 may serve as a potential target for colorectal cancer diagnosis and treatment.


Asunto(s)
Neoplasias Colorrectales/genética , Proteína Potenciadora del Homólogo Zeste 2/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Interferencia de ARN , ARN Largo no Codificante/genética , Adulto , Anciano , Animales , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Genes Reporteros , Xenoinjertos , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Transporte de ARN
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