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1.
Arch Esp Urol ; 77(4): 412-417, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38840285

RESUMO

OBJECTIVE: Advancements in medical science have improved non-metastatic renal cell carcinoma (NM-RCC) treatment strategies, but long-term survival is influenced by various factors, including perioperative blood transfusion. This study aims to analyse prognostic factors in patients with NM-RCC after radical nephrectomy. METHODS: From January 2018 to December 2021, a total of 132 patients with NM-RCC after radical nephrectomy were studied. According to 2-year follow-up data, the patients were categorised into case (with poor outcomes, including pneumothorax, renal issues, recurrence or death) and control groups. Data on demographics, clinical characteristics and perioperative blood transfusion were collected, and key prognostic factors were identified through logistic regression. RESULTS: A total of 32 patients with poor prognosis were included in the case group, accounting for 24.24% (32/132), and 100 patients without poor prognosis were included in the control group, accounting for 75.76% (100/132). Tumour stage, tumour size and perioperative blood transfusion were all risk factors for the prognosis of patients, and odds ratio (OR) >1. The above indicators had high predictive value for the prognosis of patients after surgery. CONCLUSIONS: The prognostic factors of patients with NM-RCC after radical nephrectomy include tumour stage, tumour size and perioperative blood transfusion, and each factor had predictive value.


Assuntos
Transfusão de Sangue , Carcinoma de Células Renais , Neoplasias Renais , Nefrectomia , Assistência Perioperatória , Humanos , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Nefrectomia/métodos , Prognóstico , Transfusão de Sangue/estatística & dados numéricos , Idoso
2.
J Magn Reson ; 364: 107711, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38879928

RESUMO

In the design of ultrahigh field nuclear magnetic resonance (NMR) superconducting magnets, it typically requires a high homogeneous magnetic field in the diameter of spherical volume (DSV) to obtain high spectrum resolution. However, shimming technique presents challenges due to the magnet bore space limitations, as accurate measurement of magnetic field distribution is very difficult, especially for customized micro-bore magnets. In this study, we introduced an active shimming method that utilized iterative adjustment of shim coil currents to improve the magnetic field homogeneity based on the full width at half maximum (FWHM) of the spectrum. The proposed method can determine the optimal set of currents for shim coils, effectively enhancing spatial field homogeneity by converging the FWHM. Experimental validation on a 25 T NMR superconducting magnet demonstrated the efficacy of the proposed method. Specifically, the active shimming method improved the field homogeneity of a 10 mm DSV from 7.09 ppm to 2.27 ppm with only four shim coils, providing a superior magnetic field environment for solid NMR and further magnetic resonance imaging (MRI) experiment. Furthermore, the proposed method can be promoted to more customized micro-bore magnets that require high magnetic field homogeneity.

3.
J Drug Target ; : 1-13, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38884143

RESUMO

Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.

4.
Insights Imaging ; 15(1): 161, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913225

RESUMO

OBJECTIVES: The clinical decision-making regarding choosing surgery alone (SA) or surgery followed by postoperative adjuvant chemotherapy (SPOCT) in esophageal squamous cell carcinoma (ESCC) remains controversial. We aim to propose a pre-therapy PET/CT image-based deep learning approach to improve the survival benefit and clinical management of ESCC patients. METHODS: This retrospective multicenter study included 837 ESCC patients from three institutions. Prognostic biomarkers integrating six networks were developed to build an ESCC prognosis (ESCCPro) model and predict the survival probability of ESCC patients treated with SA and SPOCT. Patients who did not undergo surgical resection were in a control group. Overall survival (OS) was the primary end-point event. The expected improvement in survival prognosis with the application of ESCCPro to assign treatment protocols was estimated by comparing the survival of patients in each subgroup. Seven clinicians with varying experience evaluated how ESCCPro performed in assisting clinical decision-making. RESULTS: In this retrospective multicenter study, patients receiving SA had a median OS 9.2 months longer than controls. No significant differences in survival were found between SA patients with predicted poor outcomes and the controls (p > 0.05). It was estimated that if ESCCPro was used to determine SA and SPOCT eligibility, the median OS in the ESCCPro-recommended SA group and SPOCT group would have been 15.3 months and 24.9 months longer, respectively. In addition, ESCCPro also significantly improved prognosis accuracy, certainty, and the efficiency of clinical experts. CONCLUSION: ESCCPro assistance improved the survival benefit of ESCC patients and the clinical decision-making among the two treatment approaches. CRITICAL RELEVANCE STATEMENT: The ESCCPro model for treatment decision-making is promising to improve overall survival in ESCC patients undergoing surgical resection and patients undergoing surgery followed by postoperative adjuvant chemotherapy. KEY POINTS: ESCC is associated with a poor prognosis and unclear ideal treatments. ESCCPro predicts the survival of patients with ESCC and the expected benefit from SA. ESCCPro improves clinicians' stratification of patients' prognoses.

5.
Med Sci Monit ; 30: e943748, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853414

RESUMO

BACKGROUND This study embarked on an innovative exploration to elucidate the effects of integrating electroacupuncture (EA) with motor training (MT) on enhancing corticospinal excitability and motor learning. Central to this investigation is the interplay between homeostatic and non-homeostatic metaplasticity processes, providing insights into how these combined interventions may influence neural plasticity and motor skill acquisition. MATERIAL AND METHODS The investigation enrolled 20 healthy volunteers, subjecting them to 4 distinct interventions to parse out the individual and combined effects of EA and MT. These interventions were EA alone, MT alone, EA-priming followed by MT, and MT-priming followed by EA. The assessment of changes in primary motor cortex (M1) excitability was conducted through motor-evoked potentials (MEPs), while the grooved pegboard test (GPT) was used to evaluate alterations in motor performance. RESULTS The findings revealed that EA and MT independently contributed to enhanced M1 excitability and motor performance. However, the additional priming with EA or MT did not yield further modulation in MEPs amplitudes. Notably, EA-priming was associated with improved GPT completion times, underscoring its potential in facilitating motor learning. CONCLUSIONS The study underscores that while EA and MT individually augment motor cortex excitability and performance, their synergistic application does not further enhance or inhibit cortical excitability. This points to the involvement of non-homeostatic metaplasticity mechanisms. Nonetheless, EA emerges as a critical tool in preventing M1 overstimulation, thereby continuously fostering motor learning. The findings call for further research into the strategic application of EA, whether in isolation or with MT, within clinical settings to optimize rehabilitation outcomes.


Assuntos
Eletroacupuntura , Potencial Evocado Motor , Voluntários Saudáveis , Aprendizagem , Córtex Motor , Estimulação Magnética Transcraniana , Humanos , Eletroacupuntura/métodos , Masculino , Córtex Motor/fisiologia , Aprendizagem/fisiologia , Feminino , Potencial Evocado Motor/fisiologia , Adulto , Estimulação Magnética Transcraniana/métodos , Plasticidade Neuronal/fisiologia , Adulto Jovem , Destreza Motora/fisiologia , Tratos Piramidais/fisiologia
6.
Food Chem Toxicol ; : 114826, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897284

RESUMO

OBJECTIVE: Aortic dissection (AD) is a prevalent and acute clinical catastrophe characterized by abrupt manifestation, swift progression, and elevated fatality rates. Despite smoking being a significant risk factor for AD, the precise pathological process remains elusive. This investigation endeavors to explore the mechanisms by which smoking accelerates AD through ferroptosis induction. METHODOLOGY: In this novel study, we detected considerable endothelial cell death by ferroptosis within the aortic inner lining of both human AD patients with a smoking history and murine AD models induced by ß-aminopropionitrile, angiotensin II, and nicotine. Utilizing bioinformatic approaches, we identified microRNAs regulating the expression of the ferroptosis inhibitor Glutathione peroxidase 4 (GPX4). Nicotine's impact on ferroptosis was further assessed in human umbilical vein endothelial cells (HUVECs) through modulation of miR-1909-5p. Additionally, the therapeutic potential of miR-1909-5p antagomir was evaluated in vivo in nicotine-exposed AD mice. FINDINGS: Our results indicate a predominance of ferroptosis over apoptosis, pyroptosis, and necroptosis in the aortas of AD patients who smoke. Nicotine exposure instigated ferroptosis in HUVECs, where the miR-1909-5p/GPX4 axis was implicated. Modulation of miR-1909-5p in these cells revealed its regulatory role over GPX4 levels and subsequent endothelial ferroptosis. In vivo, miR-1909-5p suppression reduced ferroptosis and mitigated AD progression in the murine model. CONCLUSIONS: Our data underscore the involvement of the miR-1909-5p/GPX4 axis in the pathogenesis of nicotine-induced endothelial ferroptosis in AD.

7.
Opt Express ; 32(11): 18453-18471, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859000

RESUMO

Camera calibration is very important when planning machine vision tasks. Calibration may involve 3D reconstruction, size measurement, or careful target positioning. Calibration accuracy directly affects the accuracy of machine vision. The parameters in many image distortion models are usually applied to all image pixels. However, this may be associated with rather high pixel reprojection errors at image edges, compromising camera calibration accuracy. In this paper, we present a new camera calibration optimization algorithm that features a step function that splits images into center and edge regions. First, based on the increasing pixel reprojection errors according to the pixel distance away from the image center, we gave a flexible method to divide an image into two regions, center and boundary. Then, the algorithm automatically determines the step position, and the calibration model is rebuilt. The new model can calibrate the distortions at the center and boundary regions separately. Optimized by the method, the number of distortion parameters in the old model is doubled, and different parameters represent different distortions within two regions. In this way, our method can optimize traditional calibration models, which define a global model to describe the distortion of the whole image and get a higher calibration accuracy. Experimentally, the method significantly improved pixel reprojection accuracy, particularly at image edges. Simulations revealed that our method was more flexible than traditional methods.

8.
Chin Med J (Engl) ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716704

RESUMO

BACKGROUND: This systematic review aimed to examine whether dual-task (DT) training was superior to single-task (ST) training in improving DT walking, balance and cognitive function for individuals with Parkinson's disease (PD). METHODS: Literature search was performed in the following electronic databases: PubMed, the Cochrane Library, Web of Science, and Metstr covering inception to May 10, 2023. And in order to facilitate comparison across trials, we calculated the effect size (Hedges' g) of gait, balance, cognitive, and other parameters under both ST and DT conditions, using the mean change score and standard deviation (SD) of change score of the experimental and control groups. Randomized controlled trials that examined the effects of DT motor and cognitive training in individuals with Parkinson's disease were included for this systematic review. RESULTS: A total of 335 participants recruited from six articles (five studies) were involved in this review. In terms of walking function, only double support time and stride time variability showed significant between-group difference (Hedges' g = 0.34, 0.18, respectively). Compared to ST training group, DT training group had a more improvement effect in laboratory balance measurement (Hedges' g = 0.18, 0.25), but no significant improvement in clinical balance measurement. No significant between-group differences were observed, thus its training effect on cognitive function was inconclusive. CONCLUSIONS: The DT training failed to achieve promising results better than ST training in improving DT walking and balance functions for individuals with PD. Any firm conclusion cannot be drawn at present, due to the limited number of eligible publications. Larger sample size and high-quality studies are needed to investigate the effectiveness of DT training in individuals with PD.

9.
PLoS One ; 19(5): e0300746, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722916

RESUMO

Wheat is a major grain crop in China, accounting for one-fifth of the national grain production. Drought stress severely affects the normal growth and development of wheat, leading to total crop failure, reduced yields, and quality. To address the lag and limitations inherent in traditional drought monitoring methods, this paper proposes a multimodal deep learning-based drought stress monitoring S-DNet model for winter wheat during its critical growth periods. Drought stress images of winter wheat during the Rise-Jointing, Heading-Flowering and Flowering-Maturity stages were acquired to establish a dataset corresponding to soil moisture monitoring data. The DenseNet-121 model was selected as the base network to extract drought features. Combining the drought phenotypic characteristics of wheat in the field with meteorological factors and IoT technology, the study integrated the meteorological drought index SPEI, based on WSN sensors, and deep image learning data to build a multimodal deep learning-based S-DNet model for monitoring drought stress in winter wheat. The results show that, compared to the single-modal DenseNet-121 model, the multimodal S-DNet model has higher robustness and generalization capability, with an average drought recognition accuracy reaching 96.4%. This effectively achieves non-destructive, accurate, and rapid monitoring of drought stress in winter wheat.


Assuntos
Aprendizado Profundo , Secas , Triticum , Triticum/crescimento & desenvolvimento , Triticum/fisiologia , Estações do Ano , China , Estresse Fisiológico
10.
Front Cell Infect Microbiol ; 14: 1380678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817445

RESUMO

Introduction: The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective treatment. Here, we describe the molecular epidemiology and antimicrobial resistance profiles of K. pneumoniae and CRKP isolates from hospitalized patients in different regions of China. Methods: A total of 219 K. pneumoniae isolates from 26 hospitals in 19 provinces of China were collected during 2019-2020. Antimicrobial susceptibility tests, multilocus sequence typing were performed, antimicrobial resistance genes were detected by polymerase chain reaction (PCR). Antimicrobial resistance profiles were compared between different groups. Results: The resistance rates of K. pneumoniae isolates to imipenem, meropenem, and ertapenem were 20.1%, 20.1%, and 22.4%, respectively. A total of 45 CRKP isolates were identified. There was a significant difference in antimicrobial resistance between 45 CRKP and 174 carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains, and the CRKP isolates were characterized by the multiple-drug resistance phenotype.There were regional differences among antimicrobial resistance rates of K. pneumoniae to cefazolin, chloramphenicol, and sulfamethoxazole,which were lower in the northwest than those in north and south of China.The mostcommon sequence type (ST) was ST11 (66.7% of the strains). In addition, we detected 13 other STs. There were differences between ST11 and non-ST11 isolates in the resistance rate to amikacin, gentamicin, latamoxef, ciprofloxacin, levofloxacin, aztreonam, nitrofurantoin, fosfomycin, and ceftazidime/avibactam. In terms of molecular resistance mechanisms, the majority of the CRKP strains (71.1%, 32/45) harbored blaKPC-2, followed by blaNDM (22.2%, 10/45). Strains harboring blaKPC or blaNDM genes showed different sensitivities to some antibiotics. Conclusion: Our analysis emphasizes the importance of surveilling carbapenem-resistant determinants and analyzing their molecular characteristics for better management of antimicrobial agents in clinical use.


Assuntos
Antibacterianos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Humanos , China/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/epidemiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Masculino , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Feminino , Pessoa de Meia-Idade , Idoso , Hospitalização , Adulto , Carbapenêmicos/farmacologia
11.
Int Immunopharmacol ; 134: 112141, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38733819

RESUMO

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.


Assuntos
Anticorpos Antivirais , Inteligência Artificial , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinas de Produtos Inativados , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Feminino , Vacinas contra COVID-19/imunologia , Masculino , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Adulto , Vacinas de Produtos Inativados/imunologia , Anticorpos Antivirais/sangue , Estudos Prospectivos , Imunidade Humoral , Anticorpos Neutralizantes/sangue , Eficácia de Vacinas , Imunização Secundária , Aprendizado de Máquina , Idoso , Adulto Jovem , Imunidade Celular
12.
Chem Commun (Camb) ; 60(43): 5650-5653, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38726591

RESUMO

Developing an intermediate-temperature solid oxide fuel cell (IT-SOFC) is one of the most promising ways of achieving carbon neutrality, but its air-electrode is restricted by the conflict between the sluggish catalytic activity and durability. Herein, an A-site high-entropy perovskite composite La0.2Ba0.2Sr0.2Ca0.2Ce0.2-xCoO3-δ-xCeO2 (LBSCCC-CeO2) air-electrode material is fabricated via a one-step self-constructing strategy, which shows excellent oxygen reduction activity and stability due to the high-entropy structure and the synergy effect between LBSCCC and interfacial CeO2. This work provides a new way of fabricating high-performance air-electrodes in IT-SOFCs.

13.
Int J Infect Dis ; 145: 107075, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38697605

RESUMO

OBJECTIVES: To assess the dynamics of the anti-SARS-CoV-2 IgG antibody levels and their efficacy against COVID-19. METHODS: We conducted a longitudinal serological analysis of 852 breakthrough COVID-19 infections among the community-based population in Yichang, China. Anti-SARS-CoV-2 IgG levels were measured by chemiluminescence at approximately 3, 4, and 9 months after infection. A linear mixed model predicted IgG antibody decline over 18 months. The effectiveness of antibodies in preventing symptomatic and severe infections was determined using an existing meta-regression model. RESULTS: IgG antibodies slowly declined after breakthrough infections. Initially high at around 3 months (339.44 AU/mL, IQR: 262.78-382.95 AU/mL), levels remained significant at 9 months (297.74 AU/mL, IQR: 213.22-360.62 AU/mL). The elderly (≥60 years) had lower antibody levels compared to the young (<20 years) (P < 0.001). The protective efficacy of antibodies against symptomatic and severe infections was lower in the elderly (≥60 years) (78.34% and 86.33%) compared to the young (<20 years) (96.56% and 98.75%) after 1 year. CONCLUSION: The study indicated a slow decline in anti-SARS-CoV-2 IgG antibodies, maintaining considerable efficacy for over 1 year. However, lower levels in the elderly suggest reduced protective effects, underscoring the need for age-specific vaccination strategies.


Assuntos
Anticorpos Antivirais , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Estudos Longitudinais , Masculino , Adulto , Feminino , Adulto Jovem , Idoso , Adolescente , Infecções Irruptivas
14.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731807

RESUMO

Fat tissue-a vital energy storage organ-is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p-PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.


Assuntos
Adipócitos , Diferenciação Celular , MicroRNAs , Fosfolipase C beta , RNA Circular , Animais , Adipócitos/metabolismo , Adipócitos/citologia , Diferenciação Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfolipase C beta/metabolismo , Fosfolipase C beta/genética , RNA Circular/genética , RNA Circular/metabolismo , Ovinos , Transdução de Sinais
15.
mSphere ; 9(6): e0018224, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38738873

RESUMO

The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the "last resort" for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR. We first demonstrated that the combination of berberine (BBR) and EDTA substantially restored COL sensitivity against COL-resistant Salmonella and Escherichia coli. Molecular docking indicated that BBR can interact with MCR-1 and the efflux pump system AcrAB-TolC, and BBR combined with EDTA downregulated the expression level of mcr-1 and tolC. Mechanically, BBR combined with EDTA could increase bacterial membrane damage, inhibit the function of multidrug efflux pump, and promote oxidative damage, thereby boosting the action of COL. In addition, transcriptome analysis found that the combination of BBR and EDTA can accelerate the tricarboxylic acid cycle, inhibit cationic antimicrobial peptide (CAMP) resistance, and attenuate Salmonella virulence. Notably, the combination of BBR and EDTA with COL significantly reduced the bacterial load in the liver and spleen of a mice model infected with Salmonella. Our findings revealed that BBR and EDTA can be used as adjuvants collectively with COL to synergistically reverse the COL resistance of bacteria. IMPORTANCE: Colistin is last-resort antibiotic used to treat serious clinical infections caused by MDR bacterial pathogens. The recent emergence of transferable plasmid-mediated COL resistance gene mcr-1 has raised the specter of a rapid worldwide spread of COL resistance. Coupled with the fact of barren antibiotic development pipeline nowadays, a critical approach is to revitalize existing antibiotics using antibiotic adjuvants. Our research showed that berberine combined with EDTA effectively reversed COL resistance both in vivo and in vitro through multiple modes of action. The discovery of berberine in combination with EDTA as a new and safe COL adjuvant provides a therapeutic regimen for combating Gram-negative bacteria infections. Our findings provide a potential therapeutic option using existing antibiotics in combination with antibiotic adjuvants and address the prevalent infections caused by MDR Gram-negative pathogens worldwide.


Assuntos
Antibacterianos , Berberina , Colistina , Ácido Edético , Escherichia coli , Salmonella , Colistina/farmacologia , Berberina/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Antibacterianos/farmacologia , Animais , Camundongos , Ácido Edético/farmacologia , Salmonella/efeitos dos fármacos , Salmonella/genética , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Proteínas de Escherichia coli/genética , Simulação de Acoplamento Molecular , Farmacorresistência Bacteriana/genética , Quimioterapia Combinada , Camundongos Endogâmicos BALB C , Sinergismo Farmacológico
16.
mSystems ; 9(6): e0010924, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38695565

RESUMO

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.


Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Escherichia coli , Testes de Sensibilidade Microbiana , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Animais , Bactérias Gram-Negativas/efeitos dos fármacos , Camundongos , Bambermicinas/farmacologia
17.
PLoS Pathog ; 20(5): e1012187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718038

RESUMO

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Klebsiella pneumoniae , RNA Bacteriano , Pequeno RNA não Traduzido , beta-Lactamases , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Regulação Bacteriana da Expressão Gênica , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética
18.
Infect Drug Resist ; 17: 1803-1810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741944

RESUMO

Background: Gordonia terrae is an opportunistic pathogen that rarely causes clinical infections. Here, we first report a case of spontaneous bacterial peritonitis in patients with hepatitis C cirrhosis caused by Gordonia terrea. Case Presentation: A 71-year-old male patient was diagnosed with spontaneous bacteria peritonitis secondary to hepatitis C cirrhosis. The result of bacterial culture in ascites was positive, and the pathogenic bacteria was preliminarily identified as the Gordonia genus by matrix-assisted laser desorption ionization-time of flight mass spectrometry. After 16S rRNA sequencing analysis, it was determined to be the Gordonia terrea. Symptoms relieved after treatment with ceftazidime. Conclusion: This case indicates that the clinical infections caused by Gordonia terrea should be brought to the forefront. Accurate and rapid bacterial identification results are highly beneficial to the diagnosis and therapeutic regime.

19.
Zhen Ci Yan Jiu ; 49(5): 480-486, 2024 May 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38764119

RESUMO

OBJECTIVES: To observe the activation state and neuronal types of somatosensory cortex and the primary motor cortex induced by electroacupuncture (EA) stimulation of "Sibai" (ST2) and "Quanliao" (SI18) acupoints in mice. METHODS: Male C57BL/6J mice were randomly divided into blank control and EA groups, with 6 mice in each group. Rats of the EA group received EA stimulation (2 Hz, 0.6 mA) at ST2 and SI18 for 30 minutes. Samples were collected after EA intervention, and immunofluorescence staining was performed to quantify the expression of the c-Fos gene (proportion of c-Fos positive cells) in the somatosensory cortex and primary motor cortex. The co-labelled cells of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and gamma-aminobutyric acid (GABA) in the somatosensory cortex and primary motor cortex were observed and counted by using microscope after immunofluorescence staining. Another 10 mice were used to detect the calcium activity of excitatory neurons in the somatosensory cortex and primary motor cortex by fiber photometry. RESULTS: In comparison with the blank control group, the number of c-Fos positive cells, and the proportion of c-Fos and CaMKⅡ co-labelled cells in both the somatosensory cortex and primary motor cortex were significantly increased after EA stimulation (P<0.05). No significant changes were found in the proportion of c-Fos and GABA co-labeled cells in both the somatosensory cortex and primary motor cortex after EA. Results of fiber optic calcium imaging technology showed that the spontaneous calcium activity of excitatory neurons in both somatosensory cortex and primary motor cortex were obviously increased during EA compared with that before EA (P<0.01), and strikingly reduced after cessation of EA compared with that during EA (P<0.05). CONCLUSIONS: Under physiological conditions, EA of ST2 and SI18 can effectively activate excitatory neurons in the somatosensory cortex and primary motor cortex.


Assuntos
Pontos de Acupuntura , Eletroacupuntura , Camundongos Endogâmicos C57BL , Neurônios , Animais , Masculino , Camundongos , Neurônios/metabolismo , Córtex Sensório-Motor/metabolismo , Humanos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Córtex Motor/metabolismo , Córtex Somatossensorial/metabolismo
20.
Opt Express ; 32(7): 12816-12823, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571093

RESUMO

A tunable non-polarizing optical bandpass filter structure, comprising a prism pair coupled planar optical waveguide (POW), is demonstrated, by changing the incident angle of the filter. Experimental measurements show that pass bands for both TM and TE polarized waves are present in the filter simultaneously, and the two passbands overlap on each other. The overlapping of the two passbands can be sustainable for the peak wavelength from 623 to 852 nm as the incident angle of the light tuned within 2°. This POW based optical bandpass filter can be potentially applicable in various fields of optical and laser spectroscopies.

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