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1.
Artículo en Inglés | MEDLINE | ID: mdl-38943539

RESUMEN

OBJECTIVES: To characterize blaNDM-carrying Salmonella recovered from a pig slaughterhouse. METHODS: In this study, 46 environment samples were collected from a slaughterhouse in China, and screened for carbapenem-resistant Enterobacterales. WGS, antimicrobial susceptibility testing and conjugation experiments were carried out to identify the isolates' resistance phenotypes and genetic characteristics. The phylogenetic relatedness of the Salmonella isolates obtained in this study and Salmonella (ST34 and ST29) in GenBank was determined. RESULTS: Two ST34 Salmonella Typhimurium and one ST29 Salmonella Stanley, recovered from three environmental samples (6.52%), were positive for blaNDM-1 and blaNDM-5, respectively. The two ST34 S. Typhimurium strains exhibited a close relationship (10-36 SNPs) with two human-derived blaNDM-1-bearing isolates from China (Hong Kong and Guangxi Province) and two blaNDM-negative ST34 Salmonella strains from the UK. The blaNDM-1 genes were located on IncHI2/ST3 plasmids. The capture of blaNDM-1 by the IncHI2/ST3 plasmid seems to be due to homologous recombination mediated by circular structures, as the genetic arrangements of the blaNDM-1 gene contain two IS26 elements of the same orientation. The blaNDM-5 gene was also carried by the IncHI2/ST3 plasmid, which shares highly similar structures with other blaNDM-5-bearing IncHI2/ST3 plasmids from other sources (fish, chicken, duck, human). CONCLUSIONS: This is the first report of a blaNDM-5-carrying IncHI2/ST3 plasmid in Salmonella. The clonal spread of NDM-1-producing ST34 S. Typhimurium across human and animal-associated environments, and the widespread dissemination of epidemic blaNDM-5-carrying IncHI2/ST3 plasmids among Enterobacteriaceae in China indicate the potential of further dissemination of blaNDM among Salmonella, which poses a threat to public health.

2.
J Transl Med ; 21(1): 563, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612586

RESUMEN

BACKGROUND: Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms. METHODS: Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting. RESULTS: NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA. CONCLUSION: NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.


Asunto(s)
Plexo Braquial , Neuralgia , Masculino , Ratas , Animales , Ratas Sprague-Dawley , Neuralgia/complicaciones , Médula Espinal , Atrofia
3.
Molecules ; 28(13)2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37446582

RESUMEN

The use of coal as a precursor for producing hard carbon is favored due to its abundance, low cost, and high carbon yield. To further optimize the sodium storage performance of hard carbon, the introduction of heteroatoms has been shown to be an effective approach. However, the inert structure in coal limits the development of heteroatom-doped coal-based hard carbon. Herein, coal-based P-doped hard carbon was synthesized using Ca3(PO4)2 to achieve homogeneous phosphorus doping and inhibit carbon microcrystal development during high-temperature carbonization. This involved a carbon dissolution reaction where Ca3(PO4)2 reacted with SiO2 and carbon in coal to form phosphorus and CO. The resulting hierarchical porous structure allowed for rapid diffusion of Na+ and resulted in a high reversible capacity of 200 mAh g-1 when used as an anode material for Na+ storage. Compared to unpretreated coal-based hard carbon, the P-doped hard carbon displayed a larger initial coulombic efficiency (64%) and proportion of plateau capacity (47%), whereas the unpretreated carbon only exhibited an initial coulombic efficiency of 43.1% and a proportion of plateau capacity of 29.8%. This work provides a green, scalable approach for effective microcrystalline regulation of hard carbon from low-cost and highly aromatic precursors.


Asunto(s)
Fosfatos , Dióxido de Silicio , Porosidad , Fósforo , Carbono , Carbón Mineral , Iones
4.
Anal Chem ; 93(22): 7860-7869, 2021 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-34043326

RESUMEN

We propose a novel approach for building a classification/identification framework based on the full complement of RNA post-transcriptional modifications (rPTMs) expressed by an organism at basal conditions. The approach relies on advanced mass spectrometry techniques to characterize the products of exonuclease digestion of total RNA extracts. Sample profiles comprising identities and relative abundances of all detected rPTM were used to train and test the capabilities of different machine learning (ML) algorithms. Each algorithm proved capable of identifying rigorous decision rules for differentiating closely related classes and correctly assigning unlabeled samples. The ML classifiers resolved different members of the Enterobacteriaceae family, alternative Escherichia coli serotypes, a series of Saccharomyces cerevisiae knockout mutants, and primary cells of the Homo sapiens central nervous system, which shared very similar genetic backgrounds. The excellent levels of accuracy and resolving power achieved by training on a limited number of classes were successfully replicated when the number of classes was significantly increased to escalate complexity. A dendrogram generated from ML-curated data exhibited a hierarchical organization that closely resembled those afforded by established taxonomic systems. Finer clustering patterns revealed the extensive effects induced by the deletion of a single pivotal gene. This information provided a putative roadmap for exploring the roles of rPTMs in their respective regulatory networks, which will be essential to decipher the epitranscriptomics code. The ubiquitous presence of RNA in virtually all living organisms promises to enable the broadest possible range of applications, with significant implications in the diagnosis of RNA-related diseases.


Asunto(s)
Algoritmos , ARN , Análisis por Conglomerados , Humanos , Saccharomyces cerevisiae/genética
5.
Exp Cell Res ; 397(2): 112360, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-33188851

RESUMEN

It is well established that exercise could protect against myocardial infarction (MI). Previously, we found that epoxyeicosatrienoic acids (EETs) could be induced by exercise and has been found to protect against MI via promoting angiogenic function of endothelial progenitor cells (EPCs). However, the underling mechanism of EETs in promoting EPC functions is unclear. C57BL/6 mice were fed with a novel soluble epoxide hydrolase inhibitor (sEHi), TPPU, to increase EET levels, for 1 week before undergoing MI surgery. Mice were then subjected to exercise training for 4 weeks. Bone marrow-derived EPCs were isolated and cultured in vitro. Exercise upregulated miR-126 expression but downregulated the protein levels of its target gene, Spred1, in EPCs from MI mice. TPPU further enhanced the effects of exercise on EPCs. Spred1 overexpression abolished the protective effects of TPPU on EPC functions. Downregulation of miR-126 by antagomiR-126 impaired the inhibitor effects of TPPU on Spred1 mRNA and protein expression. Additionally, TPPU upregulated miR-126 is partially mediated through ERK/p38 MAPK pathway. This study showed that sEHi promoted miR-126 expression, which might be related to the beneficial effect of sEHi on EPC functions in MI mice under exercise conditions, by increasing ERK and p38 MAPK phosphorylation and inhibiting Spred1.


Asunto(s)
Células Progenitoras Endoteliales/citología , Epóxido Hidrolasas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , MicroARNs/metabolismo , Infarto del Miocardio/terapia , Neovascularización Patológica/prevención & control , Condicionamiento Físico Animal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Células Cultivadas , Células Progenitoras Endoteliales/metabolismo , Epóxido Hidrolasas/genética , Quinasas MAP Reguladas por Señal Extracelular/genética , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/genética
6.
Respirology ; 26(2): 196-203, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32954622

RESUMEN

BACKGROUND AND OBJECTIVE: The purpose of this study was to report the characteristics and long-term survival of patients with CTEPH treated in three distinct ways: PEA, BPA and medical therapy. METHODS: Patients diagnosed with CTEPH were included in the registry that was set up in 18 centres from August 2009 to July 2018. The characteristics and survival of patients with CTEPH receiving the different treatments were reported. Prognostic factors were evaluated by Cox regression model. RESULTS: A total of 593 patients with CTEPH were included. Eighty-one patients were treated with PEA, 61 with BPA and 451 with drugs. The estimated survival rates at 1, 3, 5 and 8 years were, respectively, 95.2%, 84.6%, 73.4% and 66.6% in all patients; 92.6%, 89.6%, 87.5% and 80.2% in surgical patients; and 95.4%, 88.3%, 71.0% and 64.1% in medically treated patients. The estimated survival rates at 1, 3, 5 and 7 years in patients treated with BPA were 96.7%, 88.1%, 70.0% and 70.0%, respectively. For all patients, PEA was an independent predictor of survival. Other independent risk factors were CHD, cardiac index, PVR, big endothelin-1, APE and 6MWD. CONCLUSION: This is the first multicentre prospective registry reporting baseline characteristics and estimated survival of patients with CTEPH in China. The long-term survival rates are similar to those of patients in the international and Spanish registries. PEA is an independent predictor of survival.


Asunto(s)
Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/mortalidad , Embolia Pulmonar/complicaciones , Embolia Pulmonar/mortalidad , Angioplastia de Balón , China , Enfermedad Crónica , Endarterectomía , Endotelina-1/metabolismo , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Embolia Pulmonar/cirugía , Sistema de Registros , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
7.
Cardiovasc Drugs Ther ; 34(4): 503-513, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32394177

RESUMEN

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is a lack of effective treatments. In this meta-analysis, we assessed the efficacy and safety of inorganic nitrate in patients with HFpEF. METHODS AND RESULTS: We systematically searched PubMed, Embase, and the Cochrane Library from the inception of the database through March 2020. We included randomized controlled trials that compared the efficacy and safety of inorganic nitrate with a placebo in the treatment of patients with HFpEF. The primary outcome of the meta-analysis was exercise capacity (measured as a change in peak oxygen uptake). We also assessed the effect of inorganic nitrate on diastolic function (measured as changes in E/A and E/e', assessed by echocardiography), quality of life (estimated using the Kansas City Cardiomyopathy Questionnaire), and rest and exercise hemodynamics (measured by invasive cardiac catheterization). In the pooled data analysis, there were no significant differences in peak oxygen uptake (mL/kg/min) [mean difference (MD), 0.25; 95% CI, - 0.07 to 0.57], diastolic function [E/A-standardized mean difference (SMD), 0.51; 95% CI, - 0.17 to 1.20; or E/e'-SMD, 0.02; 95% CI, - 0.23 to 0.27], or quality of life. However, a significant change was observed in the rest and exercise hemodynamics between the inorganic nitrate and placebo treatment in HFpEF patients. No study has reported the effect of inorganic nitrate on hospitalization and mortality of patients with HFpEF. CONCLUSIONS: In patients with HFpEF, the use of inorganic nitrate is not associated with improvements in exercise capacity, diastolic function, and quality of life but is associated with significant changes in rest and exercise hemodynamics.


Asunto(s)
Fármacos Cardiovasculares/uso terapéutico , Tolerancia al Ejercicio/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Nitratos/uso terapéutico , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Anciano , Fármacos Cardiovasculares/efectos adversos , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Nitratos/efectos adversos , Consumo de Oxígeno/efectos de los fármacos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Resultado del Tratamiento
8.
Lipids Health Dis ; 17(1): 129, 2018 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-29843720

RESUMEN

BACKGROUND: It has been demonstrated that soluble epoxide hydrolase inhibitors (sEHIs) are protective against ischemia-induced lethal arrhythmias, but the mechanisms involved are unknown. Previously, we showed that sEHIs might reduce the incidence of ischemic arrhythmias by suppressing microRNA-1 (miR-1) in the myocardium. As miR-1 and miR-133 have the same proarrhythmic effects in the heart, we assumed that the beneficial effects of sEHIs might also relate to the regulation of miR-133. METHODS: A mouse model of myocardial infarction (MI) was established by ligating the coronary artery. The sEHI t-AUCB (trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) was administered daily for 7 days before MI. Myocardial infarct size and cardiac function was assessed at 24 h post-MI. The miRNA expression profiles of sham and MI mice treated with or without t-AUCB were determined by microarray and verified by real-time PCR. The incidence of arrhythmias was assessed by in vivo electrophysiologic studies. The mRNA levels of miR-133, its target genes (KCNQ1 [potassium voltage-gated channel subfamily Q member 1] and KCNH2 [potassium voltage-gated channel subfamily H member 2]), and serum response factor (SRF) were measured by real-time PCR; KCNQ1, KCNH2, and SRF protein levels were assessed by western blotting. RESULTS: We demonstrated that the treatment with sEHIs could reduce infarct size, improve cardia function, and prevent the development of cardiac arrhythmias in MI mice. The expression levels of 14 miRNAs differed between the sham and MI groups. t-AUCB treatment altered the expression of eight miRNAs: two were upregulated and six were downregulated. Of these, the muscle-specific miR-133 was downregulated in the ischemic myocardium. In line with this, up-regulation of miR-133 and down-regulation of KCNQ1 and KCNH2 mRNA/protein were observed in ischemic myocaridum, whereas administration of sEHIs produced an opposite effect. In addition, miR-133 overexpression inhibited expression of the target mRNA, whereas t-AUCB reversed the effects. Furthermore, SRF might participate in the negative regulation of miR-133 by t-AUCB. CONCLUSIONS: In MI mice, sEHI t-AUCB can repress miR-133, consequently stimulating KCNQ1 and KCNH2 mRNA and protein expression, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias.


Asunto(s)
Arritmias Cardíacas/prevención & control , Benzoatos/farmacología , MicroARNs/genética , Infarto del Miocardio/prevención & control , Miocardio/metabolismo , Urea/análogos & derivados , Animales , Arritmias Cardíacas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Canal de Potasio ERG1/genética , Regulación de la Expresión Génica , Canal de Potasio KCNQ1/genética , Masculino , Ratones , MicroARNs/efectos de los fármacos , MicroARNs/metabolismo , Infarto del Miocardio/metabolismo , ARN Mensajero , Urea/farmacología
9.
Cancer Invest ; 34(8): 378-84, 2016 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-27558529

RESUMEN

In this study, we investigated the correlation between lymphocyte to monocyte ratio (LMR) and clinical outcomes in stage I non-small cell lung cancer (NSCLC) patients. A total of 439 stage I NSCLC patients were enrolled in this study. Multivariate analyses identified LMR as an independent prognostic factor for recurrence-free survival and overall survival (hazard ratio (HR: 0.469, 95% Confidence Interval (CI): 0.325-0.677, and p < 0.001, and HR: 0.478, 95% CI: 0.332-0.688, and p < 0.001; respectively). Compared with the high LMR group, the proportion of patients who developed distant metastasis was significantly higher in the low LMR group.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Recuento de Leucocitos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Linfocitos , Monocitos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Periodo Preoperatorio , Pronóstico , Curva ROC , Estudios Retrospectivos
10.
Heliyon ; 10(7): e28897, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596102

RESUMEN

Although considerable research has been devoted to improving safety in university laboratories, accidents, in that environment, have still occurred frequently at the cost of serious injury or even death of laboratory personnel. Currently, few Human Reliability Analyses (HRA) have been conducted with respect to a university laboratory. The aim of the research was to conduct a reliability study relating to human behaviour in a university laboratory to explore quantitatively the causes and influencing factors relating to the frequency of laboratory accidents. Improved Cognitive Reliability and Error Analysis Method (CREAM) and improved Standardized Plant Analysis Risk HRA (SPAR-H) were employed to assess Human Error Probability (HEP) of 23 subjects. The HEP calculated through improved CREAM proved more accurate than results obtained through improved SPAR-H. Unexpectedly, the results demonstrated that under similar environmental conditions, the HEP of subjects did not decrease with an increase in educational background, including additional experimental time and experience. Moreover, environmental conditions exerted greater impact on personnel reliability than Human Inherent Factors (HIFs) in laboratories. It is anticipated that the study would provide valuable insights, in respect of research methods, and to serve as a practical basis for lowering the accident rate in university laboratories.

11.
mSystems ; 9(6): e0010924, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38695565

RESUMEN

Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time-kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on Escherichia coli (E. coli) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the E. coli outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy. In vivo studies confirmed the efficacy of colistin combined with flavomycin against MDR E. coli infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria. IMPORTANCE: Colistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs.


Asunto(s)
Antibacterianos , Colistina , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Escherichia coli , Pruebas de Sensibilidad Microbiana , Colistina/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Animales , Bacterias Gramnegativas/efectos de los fármacos , Ratones , Bambermicinas/farmacología
12.
Int J Gen Med ; 16: 3757-3768, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37649851

RESUMEN

Background: GLYATL1 is a member of the glycine-N-acyltransferase family, which catalyses acyl group transfer. The role of GLYATL1 in cancer is largely unknown; therefore, the potential value of GLYATL1 in clear cell renal cell carcinoma (ccRCC) was explored. Methods: The ccRCC gene expression profiles and clinical data were obtained from the University of California Santa Cruz Xena platform. Differential expression and survival analysis were performed using R software. Samples from the TIMER public database and real-world were used for validation. The potential molecular mechanism of GLYATL1 in ccRCC was explored using gene set enrichment analysis (GSEA). Results: GLYATL1 was downregulated, indicating a poor prognosis in ccRCC. Low expression of GLYATL1 was significantly associated with advanced stage and higher histological grade ccRCC. The differential expression of GLYATL1 was validated at the protein level using clinical samples and tissue microarray. The results of GSEA showed that multiple crucial signalling pathways including fatty acid metabolism, adipogenesis, oxidative phosphorylation and epithelial-mesenchymal transition were enriched. Conclusion: This study demonstrated that GLYATL1 downregulation has an unfavourable impact on the survival of patients with ccRCC. The resulting data indicated that GLYATL1 could be a potential new target for ccRCC therapy, which may be helpful for the personalized treatment of such individuals.

13.
Sci Adv ; 9(25): eade5492, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37343092

RESUMEN

Stem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that the H/ACA small nuclear ribonucleoprotein (snRNP) complex that promotes pseudouridylation of ribosomal RNA (rRNA) and ribosome biogenesis is required for oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of messenger RNAs that are enriched for CAG trinucleotide repeats and encode polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing target of rapamycin (TOR) activity to elevate ribosome levels in H/ACA snRNP complex-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.


Asunto(s)
Ribonucleoproteínas Nucleares Pequeñas , Ribosomas , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Ribosomas/metabolismo , ARN Ribosómico , Proteínas/metabolismo , Sirolimus
14.
J Org Chem ; 77(7): 3025-37, 2012 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-22369586

RESUMEN

We describe in this paper the development of a novel regioselective furanosylation methodology using partially protected furanosyl thioglycosides as central glycosylating building blocks and its application in the efficient one-pot synthesis of a series of linear and branched-type arabino- and galactofuranoside fragments structurally related to the cell wall polysaccharides of Mycobacterium tuberculosis , Streptococcus pneumoniae serostype 35A, and sugar beet.


Asunto(s)
Pared Celular/química , Mycobacterium tuberculosis/química , Oligosacáridos/química , Oligosacáridos/síntesis química , Polisacáridos/química , Polisacáridos/síntesis química , Tioglicósidos/química , Pared Celular/metabolismo , Glicosilación , Datos de Secuencia Molecular
15.
ChemSusChem ; 15(13): e202200232, 2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35244338

RESUMEN

The selective hydrogenation of 5-hydroxymethylfurfural (HMF) has been of great interest to many scientists and researchers. However, conventional hydrogenation inevitably requires the use of gaseous hydrogen as a reducing agent, which is detrimental to its storage and transport. In this regard, other economical and environmentally friendly strategies, such as catalytic transfer hydrogenation/hydrogenolysis without external molecular H2 , become more and more attractive. This Review provides the status and insight into the current research of hydrogenating HMF to high-value chemicals, using formic acid, alcohols, polymethylhydrosiloxane, water, and sodium borohydride as hydrogen donors and explains the hydrogenation mechanisms and the related hydrogenation characteristics of different hydrogen donors in the catalytic systems.


Asunto(s)
Furaldehído , Furanos , Furaldehído/análogos & derivados , Furaldehído/química , Furanos/química , Hidrógeno/química , Hidrogenación
16.
Antibiotics (Basel) ; 12(1)2022 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-36671237

RESUMEN

Colistin is a last-line antibiotic against Gram-negative pathogens. However, the emergence of colistin resistance has substantially reduced the clinical effectiveness of colistin. In this study, synergy between colistin and capric acid was examined against twenty-one Gram-negative bacterial isolates (four colistin-susceptible and seventeen colistin-resistant). Checkerboard assays showed a synergistic effect against all colistin-resistant strains [(FICI, fractional inhibitory concentration index) = 0.02-0.38] and two colistin-susceptible strains. Time-kill assays confirmed the combination was synergistic. We suggest that the combination of colistin and capric acid is a promising therapeutic strategy against Gram-negative colistin-resistant strains.

17.
Front Genet ; 12: 687236, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34539732

RESUMEN

Prostate cancer (PCa) is a serious disease that affects men's health. To date, no effective and long-lasting treatment option for this condition is available in clinical practice. ANT2 is highly expressed in a variety of hormone-related cancers, but its relationship and regulatory mechanism with PCa are unclear. In this study, we found that ANT2 expression was significantly upregulated in PCa tissues relative to control samples. Genetic knockdown of ANT2 effectively inhibited, while overexpression promoted, proliferation, migration, and invasion of PCa cells. In addition, miR-137 expression was reduced in prostate cancer tissues relative to control tissues. We identified a regulatory site for miR-137 in the 3'-UTR of ANT2 mRNA; luciferase reporter assays indicated that ANT2 is a direct target gene for miR-137. Transfecting cells with miR-137 mimics and/or an ANT2-encoding plasmid revealed that ANT2 promotes proliferation, migration, and invasion of PCa, whereas co-expression of miR-137 mimics inhibited these behaviors. These observations suggest that miR-137 mimics inhibit development of PCa by antagonizing expression of ANT2. Furthermore, tumorigenic assays in nude mice showed that miR-137 inhibitors abolished the inhibitory effect of ANT2 knockdown on PCa tumor growth. Collectively, our findings suggest that ANT2, a target gene of miR-137, is intimately involved in development of PCa, providing new evidence for the mechanism underlying pathogenesis of PCa as well as new options for targeted therapy.

18.
J Mass Spectrom ; 55(2): e4465, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31697854

RESUMEN

In this report, we explored the benefits of cyclic ion mobility (cIM) mass spectrometry in the analysis of isomeric post-transcriptional modifications of RNA. Standard methyl-cytidine samples were initially utilized to test the ability to correctly distinguish different structures sharing the same elemental composition and thus molecular mass. Analyzed individually, the analytes displayed characteristic arrival times (tD ) determined by the different positions of the modifying methyl groups onto the common cytidine scaffold. Analyzed in mixture, the widths of the respective signals resulted in significant overlap that initially prevented their resolution on the tD scale. The separation of the four isomers was achieved by increasing the number of passes through the cIM device, which enabled to fully differentiate the characteristic ion mobility behaviors associated with very subtle structural variations. The placement of the cIM device between the mass-selective quadrupole and the time-of-flight analyzer allowed us to perform gas-phase activation of each of these ion populations, which had been first isolated according to a common mass-to-charge ratio and then separated on the basis of different ion mobility behaviors. The observed fragmentation patterns confirmed the structures of the various isomers thus substantiating the benefits of complementing unique tD information with specific fragmentation data to reach more stringent analyte identification. These capabilities were further tested by analyzing natural mono-nucleotide mixtures obtained by exonuclease digestion of total RNA extracts. In particular, the combination of cIM separation and post-mobility dissociation allowed us to establish the composition of methyl-cytidine and methyl-adenine components present in the entire transcriptome of HeLa cells. For this reason, we expect that this technique will benefit not only epitranscriptomic studies requiring the determination of identity and expression levels of RNA modifications, but also metabolomics investigations involving the analysis of natural extracts that may possibly contain subsets of isomeric/isobaric species.


Asunto(s)
Espectrometría de Movilidad Iónica/métodos , Espectrometría de Masas/métodos , Ribonucleótidos/análisis , Células HeLa , Humanos , Isomerismo , Ribonucleótidos/química
19.
Exp Ther Med ; 19(1): 421-427, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31885692

RESUMEN

Chest trauma accounts for ~13.5% of all traumas, and direct death from chest trauma accounts for 20-25% of all traumatic deaths. Chest trauma is the second cause of death from trauma. Frequent rib fractures, especially in patients with flail chest, often cause severe pain, chest wall softening, abnormal breathing and severe lung contusion and laceration, usually requiring thoracic surgery. In recent years, the open reduction and internal fixation treatment of rib fractures with flail chest has achieved satisfactory results, and some surgical indications have reached consensus. A number of scholars and medical centers have demonstrated the practicality and cost-effectiveness of rib fixation in flail chest, including the small incidence of pulmonary complications, the short ICU mechanical ventilation time, and the reduction of digestive tract inhibition. Open reduction and internal fixation of rib fractures involves multiple ribs. Conventional rib fractures require a large incision to achieve satisfactory exposure. Chest wall muscles, blood vessels and nerves (long thoracic and thoracodorsal nerves) are injured, resulting in a high infection rate of the incision and postoperative dysfunctions, such as limited upper limb, shoulder and back function, and long time numbness on the affected side of the chest. Therefore, the damage of muscles and nerves caused by conventional surgical methods limits the development of such surgical technique. Although the video-assisted thoracoscopic technique has become a necessary technical means for the treatment of thoracic trauma and has been applied to thoracic exploration and hemostasis, there is no report on the application of open reduction and internal fixation for rib fracture. The difficulty lies in the tightly combined bony thorax and the soft tissue of the chest wall. Therefore, experts have explored a variety of minimally invasive surgical methods for the flail chest. The current status and research progress of minimally invasive surgery for thoracic surgery are reviewed.

20.
Interact Cardiovasc Thorac Surg ; 28(6): 936-944, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30608581

RESUMEN

OBJECTIVES: Although primary spontaneous pneumothorax (PSP) is an extremely frequent pathology, there is still no clear consensus on the treatment for these patients. We performed a strict meta-analysis on the effectiveness of manual aspiration (MA) compared to chest tube drainage (CTD) for the treatment of PSP. METHODS: A literature search was performed on PubMed, EMBASE and the Cochrane Library to identify randomized controlled trials comparing MA with CTD for the treatment of PSP. Independent reviewers evaluated the methodological quality of the included randomized controlled trials. Statistical heterogeneity among studies was quantitatively evaluated using the I-squared index. RESULTS: Five randomized controlled trials were included, and a total of 358 subjects were reported on. We found that MA was related to significantly shorter hospital stays [in days; mean difference -1.70, 95% confidence interval (CI) -2.36 to -1.04; P < 0.00001, fixed effect model] compared with CTD. However, no significant differences were found between the 2 treatments for immediate success rate (risk ratio 1.15, 95% CI 0.73-1.81; P = 0.54), 1-year recurrence rate, 1-week success rate, time of recurrence, chest surgery rate or complication rate. Subgroup analysis showed that MA can provide a significantly lower hospitalization rate than CTD with a tube size of >12 Fr or a water seal drainage system. CONCLUSIONS: On the basis of the currently available literature, MA is advantageous in the treatment of PSP because of shorter hospital stays. The subgroup analysis also indicates that MA can provide a lower hospitalization rate than CTD with a tube size of >12 Fr or a water seal drainage system. However, there are no significant differences between the 2 interventions with respect to immediate success rate, 1-year recurrence rate, 1-week success rate, time of recurrence, chest surgery rate or complication rate.


Asunto(s)
Tubos Torácicos , Drenaje/métodos , Neumotórax/terapia , Humanos , Enfermedades Pulmonares , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia
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