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BACKGROUND: While previous studies have suggested that both 'Weekend Warrior' (WW) and Regular Exercise (RE) patterns confer health benefits, the relationship between different types of physical activity (PA) and cognitive function (CF) in elderly individuals with and without depressive symptoms remains unclear. METHODS: Our study leveraged the NHANES 2011-2014 dataset, focusing on older adults. We explore the relationship between PA and CF, stratifying by depressive status. Our statistical approach included multivariable regression analysis to identify relationships between PA levels and cognitive outcomes, along with advanced techniques such as smoothed curve fitting and threshold effect analysis to examine potential nonlinear associations and identify optimal PA pattern for cognitive health. RESULTS: Analysis revealed a positive correlation between PA time and CF across all participants (ß-depressive symptomsâ¯=â¯0.03, 95â¯% CI: 0.01-0.05; ß-non-depressive symptomsâ¯=â¯0.01, 95%CI: 0.00-0.02). When comparing against the inactive, non-depressed participants partaking in WW showed improved cognitive scores (ß-WWâ¯=â¯0.22, 95â¯% CI: 0.05-0.39), similar to those engaging in RE (ß-REâ¯=â¯0.15, 95â¯% CI: 0.09-0.21). However, among the depressed participants, significant cognitive improvements were observed in the RE (ß-REâ¯=â¯0.15, 95â¯% CI: 0.04-0.25), with the WW showing less definitive results (ß-WWâ¯=â¯0.22, 95â¯% CI: -0.02-0.47). LIMITATION: The cross-sectional nature limits causal inferences. CONCLUSION: Our findings affirm the potential role of PA in enhancing CF among older subjects without depressive symptoms. However, only RE was associated with improved CF in those with depressive symptoms. These results are critical for crafting personalized PA guidelines to enhance cognitive health in the aging population.
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Background: Amid the backdrop of global aging, the increasing prevalence of cognitive decline among the elderly, particularly within the female demographic, represents a considerable public health concern. Physical activity (PA) is recognized as an effective non-pharmacological intervention for mitigating cognitive decline in older adults. However, the relationship between different PA patterns and cognitive function (CF) in elderly women remains unclear. Methods: This study utilized data from National Health and Nutrition Examination Survey (NHANES) 2011-2014 to investigate the relationships between PA, PA patterns [inactive, Weekend Warrior (WW), and Regular Exercise (RE)], and PA intensity with CF in elderly women. Multivariate regression analysis served as the primary analytical method. Results: There was a significant positive correlation between PA and CF among elderly women (ß-PA: 0.003, 95% CI: 0.000-0.006, P = 0.03143). Additionally, WW and RE activity patterns were associated with markedly better cognitive performance compared to the inactive group (ß-WW: 0.451, 95% CI: 0.216-0.685, P = 0.00017; ß-RE: 0.153, 95% CI: 0.085-0.221, P = 0.00001). Furthermore, our results indicate a progressive increase in CF with increasing PA intensity (ß-MPA- dominated: 0.16, 95% CI: 0.02-0.09, P = 0.0208; ß-VPA-dominated: 0.21, 95% CI: 0.09-0.34, P = 0.0011; ß-Total VPA: 0.31, 95% CI: -0.01-0.63, P = 0.0566). Conclusion: Our study confirms a positive association between PA and CF in elderly women, with even intermittent but intensive PA models like WW being correlated with improved CF. These findings underscore the significant role that varying intensities and patterns of PA play in promoting cognitive health among older age groups, highlighting the need for adaptable PA strategies in public health initiatives targeting this population.
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OBJECTIVE: To explore the potential value of three-dimensional fast spin echoï¼3D-SPACEï¼ combined with multilayer spiral CT ï¼MSCTï¼ in the diagnosis of knee cruciate ligament injury, to provide a new direction for the optimization of subsequent clinical diagnosis. METHODS: A total of 120 patients with knee cruciate ligament injury were treated from April 2020 to April 2021, aged from 21 to 68 with an average ofï¼41.52±4.13ï¼ years old. For all patients, separate MSCT scanner scans, 3D-SPACE sequence scans alone and 3D-SPACE sequence combined with MSCT scans were used. The injury and classification of the anterior and posterior cruciate ligament of the knee were compared, the length of the anterior-medial bundle and posterolateral bundle and its angle of the knee with the horizontal plane were observed, the diagnostic value of 3 diagnostic methods in knee cruciate ligament injury were determined. RESULTS: There was no significant difference between the 3D-SPACE sequence scan alone and the MSCT test alone on the total diagnostic rate and grading total diagnostic rateï¼P>0.05ï¼. The total diagnostic rate and grading total diagnostic rate of 3D-SPACE scan combined with MSCT were significantly higher than those of 3D-SPACE scan or MSCT aloneï¼P<0.05ï¼. The 3D-SPACE sequence scan alone and the MSCT detection alone had no significant difference in the measurement values related to the anterior and posterior cruciate ligaments of the knee jointï¼P>0.05ï¼. 3D-SPACE sequence scanning combined with MSCT detection on the knee joint anterior and posterior cruciate ligament related measurements were significantly higher than the 3D-SPACE sequence scan or MSCT detection aloneï¼P<0.05ï¼. The area under the ROC curve estimated by 3D-SPACE sequence scanning combined with MSCT was 0.960, which was significantly higher than that of 3D-SPACE sequence scanning and MSCT alone evaluating the area under the ROC curve line of 0.756 and 0.795. The combined 3D-SPACE sequence scanning and 3D-SPACE sequence scanning MSCT analysis and prediction models were statistically differentï¼Z=2.236, P<0.05ï¼, and MSCT alone and 3D-SPACE sequence scanning combined with MSCT analysis and prediction models were statistically differentï¼Z=2.653, P<0.05ï¼. CONCLUSION: The application of 3D-SPACE sequence combined with MSCT scanning for knee cruciate ligament injury can improve the diagnosis rate of patients with knee cruciate ligament injury.It can be used as a diagnostic tool for patients with knee cruciate ligament injury and is worthy of clinical application.
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Lesiones del Ligamento Cruzado Anterior , Traumatismos de la Rodilla , Ligamento Cruzado Posterior , Traumatismos de los Tejidos Blandos , Humanos , Adulto , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Artroscopía , Traumatismos de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Ligamento Cruzado Posterior/lesiones , Tomografía Computarizada Espiral , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagenRESUMEN
Background: Cognitive-Motor Dual Task (CMDT) training has been widely utilized in rehabilitation and sports practice. However, whether CMDT training can better enhance athletes' cognitive-motor performance compared to traditional single-task (ST) training remains unclear. Method: A systematic review that complied with PRISMA was carried out (Prospero registration number: CRD42023443594). The electronic databases used for the systematic literature search from the beginning through 13 June 2023, included Web of Science, Embase, PubMed, and the Cochrane Library. After obtaining the initial literature, two researchers independently assessed it based on inclusion and exclusion criteria. Finally, the included literature was analyzed to compare the differences between ST training and CMDT training. Results: After screening 2,094 articles, we included 10 acute studies and 7 chronic studies. Conclusion: This systematic review shows that athletes typically show a degradation of performance in CMDT situations as opposed to ST when evaluated transversally. However, this performance decline is notably reduced following longitudinal training in CMDT, indicating the effectiveness of sustained CMDT training in enhancing cognitive-motor performance under dual-task conditions. Our study provides new insights into the application of CMDT in the field of sports training. Practitioners can utilize CMDT to assess athletic skill levels or optimize cognitive-motor performance of athletes, taking into account the specific needs of each sport. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023443594.
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As an important virulence phenotype of Escherichia coli, the regulation mechanism of biofilm by non-coding RNA and quorum sensing system has not been clarified. Here, by transcriptome sequencing and RT-PCR analysis, we found CsrB, a non-coding RNA of the carbon storage regulation system, was positively regulated by the LuxR protein SdiA. Furthermore, ß-galactosidase reporter assays showed that SdiA enhanced promoter transcriptional activity of csrB. The consistent dynamic expression levels of SdiA and CsrB during Escherichia coli growth were also detected. Moreover, curli assays and biofilm assays showed sdiA deficiency in Escherichia coli SM10λπ or BW25113 led to a decreased formation of biofilm, and was significantly restored by over-expression of CsrB. Interestingly, the regulations of SdiA on CsrB in biofilm formation were enhanced by quorum sensing signal molecules AHLs. In conclusion, SdiA plays a crucial role in Escherichia coli biofilm formation by regulating the expression of non-coding RNA CsrB. Our study provides new insights into SdiA-non-coding RNA regulatory network involved in Escherichia coli biofilm formation.
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The pollution of heavy metals is extremely serious in China, including zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd). Heavy-metal-transporting ATPase (HMA) belongs to a subfamily of the P-ATPase family, which absorbs and transports Zn, Cu, Pb, and Cd in plants. Here, we describe a ZmHMA-encoding HMA family protein that positively regulates Cd and Zn tolerance. The real-time fluorescence quantification (RT-PCR) results revealed that ZmHMA3 had a high expression in B73, and the expression of ZmHMA3 was sensitive to Cd in yeast cells, which was related to Cd accumulation in yeast. Additionally, the Arabidopsis thaliana homologous mutants of AtHMA2 showed Cd sensitivity compared with WT. The overexpressing ZmHMA3 plants showed higher tolerance under Cd and Zn stresses than the wild type. The overexpression of ZmHMA3 led to higher Cd and Zn accumulation in tissues based on the subcellular distribution analysis. We propose that ZmHMA3 improves maize tolerance to Cd and Zn stresses by absorbing and transporting Cd and Zn ions. This study elucidates the gene function of the ZmHMA3 response to Cd and Zn stress and provides a reference for improving the characteristics of heavy metals enrichment in existing maize varieties and the plant remediation technology of heavy-metal-contaminated soil.
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Arabidopsis , Metales Pesados , Zinc , Cadmio/toxicidad , Zea mays/genética , Adenosina Trifosfatasas/genética , Plomo , Saccharomyces cerevisiae , Metales Pesados/toxicidad , Arabidopsis/genéticaRESUMEN
Haemophilus seminalis is a newly proposed species that is phylogenetically related to Haemophilus haemolyticus. The distribution of H. seminalis in the human population, its genomic diversity, and its pathogenic potential are still unclear. This study reports the finding of our comparative genomic analyses of four newly isolated Haemophilus strains (SZY H8, SZY H35, SZY H36, and SZY H68) from human sputum specimens (Guangzhou, China) along with the publicly available genomes of other phylogenetically related Haemophilus species. Based on pairwise comparisons of the 16S rRNA gene sequences, the four isolates showed <98.65% sequence identity to the type strains of all known Haemophilus species but were identified as belonging to H. seminalis, based on comparable phenotypic and genotypic features. Additionally, the four isolates showed high genome-genome relatedness indices (>95% ANI values) with 17 strains that were previously identified as either "Haemophilus intermedius" or hemin (X-factor)-independent H. haemolyticus and therefore required a more detailed classification study. Phylogenetically, these isolates, along with the two previously described H. seminalis isolates (a total of 23 isolates), shared a highly homologous lineage that is distinct from the clades of the main H. haemolyticus and Haemophilus influenzae strains. These isolates present an open pangenome with multiple virulence genes. Notably, all 23 isolates have a functional heme biosynthesis pathway that is similar to that of Haemophilus parainfluenzae. The phenotype of hemin (X-factor) independence and the analysis of the ispD, pepG, and moeA genes can be used to distinguish these isolates from H. haemolyticus and H. influenzae. Based on the above findings, we propose a reclassification for all "H. intermedius" and two H. haemolyticus isolates belonging to H. seminalis with an emended description of H. seminalis. This study provides a more accurate identification of Haemophilus isolates for use in the clinical laboratory and a better understanding of the clinical significance and genetic diversity in human environments. IMPORTANCE As a versatile opportunistic pathogen, the accurate identification of Haemophilus species is a challenge in clinical practice. In this study, we characterized the phenotypic and genotypic features of four H. seminalis strains that were isolated from human sputum specimens and propose the "H. intermedius" and hemin (X-factor)-independent H. haemolyticus isolates as belonging to H. seminalis. The prediction of virulence-related genes indicates that H. seminalis isolates carry several virulence genes that are likely to play an important role in its pathogenicity. In addition, we depict that the genes ispD, pepG, and moeA can be used as biomarkers for distinguishing H. seminalis from H. haemolyticus and H. influenzae. Our findings provide some insights into the identification, epidemiology, genetic diversity, pathogenic potential, and antimicrobial resistance of the newly proposed H. seminalis.
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Haemophilus , Hemina , Humanos , ARN Ribosómico 16S/genética , Haemophilus/genética , Haemophilus influenzae , Genómica , Filogenia , Variación GenéticaRESUMEN
Soft, conductive, and stretchable sensors are highly desirable in many applications, including artificial skin, biomonitoring patches, and so on. Recently, a combination of good electrical and mechanical properties was regarded as the most important evaluation criterion for judging whether hydrogel sensors are suitable for practical applications. Herein, we demonstrate a novel carboxylated carbon nanotube (MWCNT-COOH)-embedded P(AM/LMA)/SiO2@PANI hydrogel. The hydrogel benefits from a double-network structure (hydrogen bond cross-linking and hydrophobic connectivity network) due to the role of MWCNT-COOH and SiO2@PANI as cross-linkers, thus resulting in tough composite hydrogels. The obtained P(AM/LMA)/SiO2@PANI/MWCNT-COOH hydrogels exhibited high tensile strength (1939 kPa), super stretchability (3948.37%), and excellent strain sensitivity (gauge factor = 11.566 at 100-1100% strain). Obviously, MWCNT-COOH not only improved the electrical conductivity but also enhanced the mechanical properties of the hydrogel. Therefore, the integration of MWCNT-COOH and SiO2@PANI-based hydrogel strain sensors will display broad application in sophisticated intelligence, soft robotics, bionic prosthetics, personal health care, and other fields using inexpensive, green, and easily available biomass.
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Background: In 2022, Shanghai was seriously affected by the coronavirus disease 2019 (COVID-19) pandemic. The government implemented citywide static management for 2 months, as well as all universities in Shanghai, which changed the normal learning and living style of sports students and led to a decline in physical activity level. As the physical activity has a strong correlation with mental health, this study aimed to investigate the current state of physical activity (PA) and mental health of the students in Shanghai University of Sport. It will try to reveal the correlation between PA and depressive symptoms, anxiety symptoms, fear of COVID-19 and smartphone addiction. Methods: A cross-sectional survey was conducted on a random sample of 400 students who came from six different majors in May 2022 at the Shanghai University of Sport. Respondents completed the International Physical Activity Questionnaire Short Form (IPAQ-SF), the Chinese version of the 9-item Patient Health Questionnaire (PHQ-9), the Chinese version of the Generalized Anxiety Disorder Scale (GAD-7), the Chinese version of the COVID-19 Fear Scale (FCV- 19S), and the Smartphone Addiction Scale (SAS-SV). Demographics, PA, depressive symptoms, anxiety symptoms, fear of COVID-19, and smartphone addiction were compared. A binary logistic regression model was used for the further analysis. Results: A total of 376 college students were included in the final analysis. Binary logistics analysis showed that moderate physical activity (MPA) was negatively correlated with depression (OR = 0.95, 95%CI = 0.93-0.98), anxiety (OR = 0.97, 95%CI = 0.95-0.99), fear of COVID 19(OR = 0.99, 95%CI = 0.98-0.99)and smartphone addiction (OR = 0.94, 95%CI = 0.9-0.98) (all P < 0.05). Sedentary behavior was positively correlated with smartphone addiction (OR = 1.01, P < 0.01, 95%CI = 1.001-1.004). Conclusion: There was an association between the presence of MPA and depressive symptoms, anxiety symptoms, fear of COVID-19, smartphone addiction, and sedentary behavior associated with smartphone addiction levels. Clarifying the causal relationship between PA and mental health will require further research.
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COVID-19 , Humanos , COVID-19/epidemiología , Salud Mental , Universidades , Estudios Transversales , China/epidemiología , Estudiantes/psicología , Ejercicio FísicoRESUMEN
BACKGROUND: We have explored that quantitative PCT detection can be conducted in different sample types (whole blood and/or plasma samples) with good correlation and consistency in clinical use. These findings reduce the sample volume and turnover time of PCT detection in clinical labs. However, different hematocrit (HCT) percentages of whole blood samples may affect the final results, especially abnormal hematocrit (HCT) percentages. To overcome this problem, we established a mathematical model to modify the whole blood test results and evaluated the effects of HCT correction. METHODS: First, we prepared a preliminary experiment - various hematocrit (HCT) percentages (15% - 65%) of whole blood samples with different PCT concentrations and established a mathematic model to correct the effects of PCT detection. Then, in this paper, we evaluated the consistency with Pearson's correlation and Kappa analysis between whole bloods detected by the i-Reader S system and plasma detected by the Biomerieux system. Besides, we prepared different HCT values about 15%, 40%, 60% of 9 samples with different PCT concentrations to evaluate the effects of HCT correction Results and Conclusions: Pearson's correlative studies and Kappa analysis indicated that PCT levels measured by i-Reader S (plasma & whole blood samples) were comparable to results from the VIDAS system, and HCT correction could improve consistency of PCT detection between whole blood and plasma. Analysis of samples with abnormal HCT values showed that the mathematical correction model could offset the influences of various HCT values.
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Hematócrito , Plasma , Polipéptido alfa Relacionado con Calcitonina , Hematócrito/métodos , Humanos , Polipéptido alfa Relacionado con Calcitonina/sangreRESUMEN
Long non-coding RNAs (lncRNAs) are transcripts that are >200 nucleotides, but with no open reading frame. An increasing number of lncRNAs have been identified following the development of second-generation sequencing technologies, and they have since become a research hotspot. Functionally, they play a vital role in tumor progression, including in tumor proliferation, migration, invasion, apoptosis and acquisition of drug resistance. They regulate gene expression primarily through interaction with DNA, RNA and proteins at the epigenetic, transcriptional and post-transcriptional levels. Endogenous hypoxia-inducible factor 1α antisense RNA 2 (lncRNA HIF1A-AS2) is aberrantly expressed and involved the development/progression of various types of tumors, such as bladder cancer, glioblastoma, breast cancer and osteosarcoma. It plays a vital role in the proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transformation of various tumor cells. This review summarizes the current body of knowledge on the biological functions and related molecular mechanisms of lncRNA HIF1A-AS2 in the development/progression of human tumors and other diseases.
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N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL), a small bacterial signaling molecule secreted by Pseudomonas aeruginosa (P. aeruginosa), can block dendritic cell (DC) maturation and participate in immune escape, but the underlying mechanism is unclear. We speculate that regulation of DC maturation and function by lncRNAs may be the mechanism by which 3-O-C12-HSL inhibits the immune response. We found that 3-O-C12-HSL increased the expression level of the lncRNA NRIR, impeding monocyte-derived dendritic cell (Mo-DC) maturation. In addition, we observed the effect of NRIR on the expression of CD40, CD80, HLA-DR and IL-6. NRIR overexpression significantly reduced the expression of Mo-DC surface markers, while 3-OC12-HSL did not significantly reduce the expression of Mo-DC surface markers after NRIR knockdown. These results indicate that 3-O-C12-HSL indeed affects the differentiation and maturation of Mo-DCs through NRIR. IL-6 stimulates T cell proliferation and activation, and we found that high NRIR expression reduced IL6 levels. However, under NRIR knockdown, 3-O-C12-HSL did not decrease IL-6 expression, suggesting that 3-O-C12-HSL may affect T cell activation through NRIR. This study is the first to elucidate the important role of a lncRNA in the mechanism of 3-O-C12-HSL activity. It also provides new ideas regarding P. aeruginosa infection pathogenesis.
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4-Butirolactona/análogos & derivados , Células Dendríticas/efectos de los fármacos , Homoserina/análogos & derivados , ARN Largo no Codificante/metabolismo , 4-Butirolactona/farmacología , Estudios de Casos y Controles , Diferenciación Celular/efectos de los fármacos , Homoserina/farmacología , Humanos , Interleucina-6/metabolismo , Monocitos/metabolismo , Infecciones por Pseudomonas/metabolismo , Pseudomonas aeruginosaRESUMEN
Hydrogel-based flexible strain sensors for personal health monitoring and human-machine interaction have attracted wide interest among researchers. In this paper, hydrophobic association and nanocomposite conductive hydrogels were successfully prepared by introducing polyaniline coated silica (SiO2@PANI) core-shell particles into an acrylamide-lauryl methacrylate (P(AM/LMA)) copolymer matrix. The hydrophobic interaction between the SiO2@PANI core-shell particles and the hydrophobic LMA in the P(AM/LMA) chains induced the hydrogels with outstanding mechanical properties. Furthermore, the polyaniline on the SiO2 surface and the inorganic salt formed a conductive network, which synergistically enhanced the conductivity of the hydrogels. The obtained hydrogels integrate high tensile strength (1398 kPa), ultra-stretchability (>1000%), wonderful strain sensitivity (gauge factor = 10.407 at 100-1100% strain), quick response (300 ms), and excellent durability (>300 cycles) due to the hydrophobic association and nanocomposite effect. The prepared SiO2@PANI-P(AM/LMA) hydrogel shows high stress sensitivity to detect human movements and displays a broad application prospect in flexible strain-sensor field.
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Hidrogeles , Dióxido de Silicio , Compuestos de Anilina , Conductividad Eléctrica , HumanosRESUMEN
The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.
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Antineoplásicos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Histona Demetilasas con Dominio de Jumonji/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Proteasas Ubiquitina-Específicas/antagonistas & inhibidores , Animales , Antineoplásicos/farmacología , Benzamidas , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Inhibidores Enzimáticos/farmacología , Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Histona Demetilasas con Dominio de Jumonji/genética , Masculino , Ratones , Ratones Mutantes , Nitrilos , Fosfohidrolasa PTEN/deficiencia , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/farmacología , Feniltiohidantoína/uso terapéutico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Unión Proteica/efectos de los fármacos , Estabilidad Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/genética , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacos , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismo , Ubiquitinación/efectos de los fármacosRESUMEN
Small regulatory RNAs (sRNAs) act as key regulators in many bacterial signalling cascades. However, in P. aeruginosa, the sRNAs involved in quorum sensing (QS) regulation and their function are still largely unknown. Here, we explored how the prrH locus sRNA influences P. aeruginosa virulence in the context of the QS regulatory network. First, gain- and loss-of-function studies showed that PrrH affects pyocyanin, elastase and rhamnolipid production; biofilm formation; and swimming and swarming motility and impaired the viability of P. aeruginosa in human whole blood. Next, our investigation disclosed that LasI and PhzC/D were directly repressed by PrrH. In addition, RhlI, the key member of the rhl QS system, diminished the expression of PrrH and enhanced the expression of downstream genes. Bioinformatics analysis found two binding sites of RhlR, the transcription factor of the rhl system, on the promoter region of prrH. Further ß-galactosidase reporter and qPCR assays confirmed that PrrH was transcriptionally repressed by RhlR. Collectively, our data identified a novel RhlI/R-PrrH-LasI/PhzC/PhzD regulatory circuitry that may contribute to P. aeruginosa pathogenesis. Our findings indicate that PrrH is a quorum regulatory RNA (Qrr) in P. aeruginosa and provide new insight into PrrH's function.
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Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/patogenicidad , ARN Bacteriano/metabolismo , Proteínas Bacterianas/genética , Humanos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Percepción de Quorum , ARN Bacteriano/genética , VirulenciaRESUMEN
Conjugation is a key mechanism for horizontal gene transfer and plays an important role in bacterial evolution, especially with respect to antibiotic resistance. However, little is known about the role of donor and recipient cells in regulation of conjugation. Here, using an Escherichia coli (SM10λπ)-Pseudomonas aeruginosa (PAO1) conjugation model, we demonstrated that deficiency of lasI/rhlI, genes associated with generation of the quorum sensing signals N-acyl homoserine lactones (AHLs) in PAO1, or deletion of the AHLs receptor SdiA in the donor SM10λπ both facilitated conjugation. When using another AHLs-non-producing E. coli strain EC600 as recipient cells, deficiency of sdiA in donor SM10λπ hardly affect the conjugation. More importantly, in the presence of exogenous AHLs, the conjugation efficiency between SM10λπ and EC600 was dramatically decreased, while deficiency of sdiA in SM10λπ attenuated AHLs-inhibited conjugation. These data suggest the conjugation suppression function of AHLs-SdiA chemical signaling. Further bioinformatics analysis, ß-galactosidase reporter system and electrophoretic mobility shift assays characterized the binding site of SdiA on the promoter region of traI gene. Furthermore, deletion of lasI/rhlI or sdiA promoted traI mRNA expression in SM10λπ and PAO1 co-culture system, which was abrogated by AHLs. Collectively, our results provide new insight into an important contribution of quorum sensing system AHLs-SdiA to the networks that regulate conjugation.
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Acil-Butirolactonas/metabolismo , Conjugación Genética/efectos de los fármacos , ADN Helicasas/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Pseudomonas aeruginosa/genética , Transactivadores/metabolismo , Regulación Bacteriana de la Expresión Génica/efectos de los fármacosRESUMEN
After the publication of the article, the authors noted that they would like to add Dr Robert H. Getzenberg's name to the authors' list and as a co-corresponding author, upon the agreement of all the authors. The correct author list should be as follows: BO YIN1, MO ZHANG1, YU ZENG2,3*, YOUQIANG LI3, CHAO ZHANG1, ROBERT H. GETZENBERG3* and YONGSHENG SONG1* 1Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004; 2Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China; 3James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21087, USA Correspondence should now be addressed to: Correspondence to: Dr Yongsheng Song, Department of Urology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning 110004, P.R. China E-mail: yinbowzf@163.com Dr Robert H. Getzenberg, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21087, USA E-mail: getzenberg@outlook.com *Contributed equally [the original article was published in the International Journal of Oncology 48: 1730-1736, 2016; DOI: 10.3892/ijo.2016.3396].
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Paclitaxel frequently serves as the first-line chemotherapeutic agent for castration-resistant prostate cancer (PCa) patients. However, acquired paclitaxel-resistance almost always occurs after initial responses, and the mechanisms by which this occurs remain largely unknown. The goal of the present study was to identify differentially expressed protein(s) associated with paclitaxel-resistance and further explore the potential mechanisms involved in drug resistance. By comparing the nuclear matrix protein (NMP) patterns of DU145-TxR cells, the previously established stable paclitaxel-resistant PCa cells, with that of the parental DU145 cells using two-dimensional electrophoresis, we found that cytokeratin 18 (CK18) is downregulated in DU145-TxR cells. The downregulation of CK18 in DU145-TxR cells at mRNA, NMP and total cellular protein levels was validated by real-time RT-PCR, immunoblotting and immunofluorescence, indicating that the downregulation of CK18 was a global effect in DU145-TxR cells due to paclitaxel-resistance. Furthermore, in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of DU145-TxR cells, suggesting that these paclitaxel-resistant PCa cells possessed potent cancer stem cell (CSC)-like properties and eventually developed paclitaxel-resistance. Moreover, we determined by immunohistochemistry that CK18 expression in PCa tissues was inversely correlated with tumor grade in a statistically significant fashion, indicating a potential association of the downregulation of CK18 with tumor aggressiveness. Therefore, further study to define the potential role of CK18 may lead to novel therapy strategies as well as clinically useful biomarker for PCa patients.
Asunto(s)
Regulación hacia Abajo , Resistencia a Antineoplásicos , Queratina-18/genética , Queratina-18/metabolismo , Neoplasias de la Próstata/patología , Animales , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Humanos , Masculino , Ratones , Trasplante de Neoplasias , Paclitaxel/farmacología , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Análisis de SupervivenciaRESUMEN
N-3-(Oxododecanoyl)-L-homoserine lactone (C12) is a small bacterial signaling molecule secreted by Pseudomonas aeruginosa (PA), which activates mammalian cells through TLR4-independent mechanisms. C12 acts as an immunosuppressant and it has been shown to modulate murine bone marrow-derived dendritic cell-mediated T-helper 2 (Th2) cell polarizations in vitro. In the present study, we initially examined the impact of C12 on the maturation of human monocyte-derived dendritic cells (Mo-DCs) and the induction of regulatory T-cells (iTregs) in culture. Our findings demonstrate that C12-treated Mo-DCs failed to undergo lipopolysaccharide (LPS)-induced maturation. At the molecular level, C12 blocked the upregulation of surface molecules, including CD11c, HLA-DR, CD40, and CD80, and it switched to an interleukin (IL)-10(high), IL-12p70(low) phenotype. Moreover, C12 selectively inhibited the capacity of Mo-DCs to stimulate the proliferation of allogeneic CD4(+) T-cells. Otherwise, the C12-treated Mo-DCs promoted the generation of CD4(+)CD25(+)Foxp3(+)-induced regulatory T-cells (iTregs) and enhanced their IL-10 and transforming growth factor (TGF)-ß production associated with reduced interferon (IFN)-γ and IL-12p70 production. These findings provide new insights towards understanding the persistence of chronic inflammation in PA infection.