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1.
Cancer Innov ; 3(4): e124, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38948251

RESUMEN

Background: Increased glycolytic activity and lactate production are characteristic features of triple-negative breast cancer (TNBC). The aim of this study was to determine whether a subset of lactate-responsive genes (LRGs) could be used to classify TNBC subtypes and predict patient outcomes. Methods: Lactate levels were initially measured in different breast cancer (BC) cell types. Subsequently, MDA-MB-231 cells treated with 2-Deoxy-d-glucose or l-lactate were subjected to RNA sequencing (RNA-seq). The gene set variation analysis algorithm was utilized to calculate the lactate-responsive score, conduct a differential analysis, and establish an association with the extent of immune infiltration. Consensus clustering was then employed to classify TNBC patients. Tumor immune dysfunction and exclusion, cibersort, single-sample gene set enrichment analysis, and EPIC, were used to compare the tumor-infiltrating immune cells between TNBC subtypes and predict the response to immunotherapy. Furthermore, a prognostic model was developed by combining 98 machine learning algorithms, to assess the predictive significance of the LRG signature. The predictive value of immune infiltration and the immunotherapy response was also assessed. Finally, the association between lactate and various anticancer drugs was examined based on expression profile similarity principles. Results: We found that the lactate levels of TNBC cells were significantly higher than those of other BC cell lines. Through RNA-seq, we identified 14 differentially expressed LRGs in TNBC cells under varying lactate levels. Notably, this LRG signature was associated with interleukin-17 signaling pathway dysregulation, suggesting a link between lactate metabolism and immune impairment. Furthermore, the LRG signature was used to categorize TNBC into two distinct subtypes, whereby Subtype A was characterized by immunosuppression, whereas Subtype B was characterized by immune activation. Conclusion: We identified an LRG signature in TNBC, which could be used to predict the prognosis of patients with TNBC and gauge their response to immunotherapy. Our findings may help guide the precision treatment of patients with TNBC.

2.
Nutrition ; 125: 112500, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38964261

RESUMEN

OBJECTIVES: The purpose of the present study was to explore the latent growth trajectory of body mass index (BMI) from birth to 24 months and comprehensively analyze body composition development influencing factor in preschool children. METHODS: This ambidirectional cohort study was conducted in Tianjin, China, from 2017 to 2020, and children's regular medical check-up data from birth to 24 months were retrospectively collected. The growth models were used to fit BMI z-score trajectories for children aged 0-24 months. Crossover analysis and interaction model were used to explore the interaction of influencing factors. RESULTS: We analyzed the growth trajectories of 3217 children, of these, 1493 children with complete follow-up data were included in the influencing factors analysis. Trajectories and parental prepregnancy BMI (ppBMI) were independent factors influencing children's body composition. When paternal ppBMI ≥24 kg/m2, regardless of maternal ppBMI, the risk of overweight and obesity in senior-class children was increased. The high trajectories played a partial mediating role in the association between paternal ppBMI and body composition in preschool children. CONCLUSIONS: BMI growth in children aged 0-24 months can be divided into three latent trajectories: low, middle, and high. These trajectories and parental ppBMI were independent and interactive factors influencing children's body composition. The high trajectories played a partial mediating role in the association between paternal ppBMI and body composition in preschool children. It is necessary to pay attention to the BMI growth level of children aged 0-24 months, which plays an important role in the development of body fat in the future.

3.
Opt Lett ; 49(12): 3528-3531, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38875662

RESUMEN

The application of a liquid crystal (LC) in displays has driven the development of novel LC elements. In this Letter, polarization variable line-space (PVLS) gratings based on photoalignment are fabricated, and their variable-spacing properties are derived using the vector diffraction theory. Both transmissive and reflective PVLS gratings are fabricated to validate the correctness of the derivation. Experimental results indicate that PVLS gratings have a wider wavelength response bandwidth than that of polarization volume grating (PVG). PVLS gratings have angle selectivity, and a large incident angle causes wavelength blueshift. Additionally, the relationship between wavelength and focal length indicates its anomalous dispersion as a diffractive optical element. These results of photoalignment-based PVLS gratings provide valuable insights for the advancement of displays and have the potential to improve visual experiences.

4.
Int J Rheum Dis ; 27(6): e15205, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38873791

RESUMEN

OBJECTIVE: To construct a risk prediction model for atherosclerotic cardiovascular disease (ASCVD) in patients with hyperuricemia. METHODS: Data in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) (2007-2010). Participants from Huashan Hospital were included as an external validation. Logistic regression analysis was used to explore the relevant factors of ASCVD in patients with hyperuricemia. The discriminability of the model was evaluated using the area under the curve (AUC) statistic of the receiver operating characteristic curve. Hosmer-Lemeshow test, correction curve and decision curve analysis (DCA) were used to evaluate the model. RESULTS: A total of 389 patients collected from the NHANES were included in the final analysis. Logistic regression analysis showed that age, creatinine (Cr), glucose (Glu), serum uric acid (SUA), and history of gout were predictive factors for ASCVD in hyperuricemia (HUA) patients. These predictive factors were used to construct a nomogram. And 157 patients from NHANES were in the internal validation group and 136 patients from Huashan Hospital were in the external validation group. The AUC values of the three groups were 0.943, 0.735, and 0.664. The p values of the Hosmer-Lemeshow test were .568, .600, and .763. The calibration curve showed consistency between the nomogram and the actual observed values. The DCA curve indicated that the model has good clinical practicality. CONCLUSION: This study constructed the ASCVD risk prediction model for HUA patients, which is beneficial for medical staff to detect high-risk populations of ASCVD in the early stage.


Asunto(s)
Aterosclerosis , Biomarcadores , Técnicas de Apoyo para la Decisión , Hiperuricemia , Nomogramas , Encuestas Nutricionales , Valor Predictivo de las Pruebas , Ácido Úrico , Humanos , Hiperuricemia/sangre , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Medición de Riesgo , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Ácido Úrico/sangre , Biomarcadores/sangre , Reproducibilidad de los Resultados , Factores de Riesgo , Adulto , Anciano , Pronóstico , China/epidemiología , Curva ROC
5.
Prev Med ; 185: 108054, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38914268

RESUMEN

OBJECTIVE: This study is part of a programmatic investigation of rural disparities in cigarette smoking examining disparities in smoking prevalence and for the first-time quit ratios among adult women of reproductive age (18-44 years), a highly vulnerable population due to risk for multigenerational adverse effects. METHODS: Data came from 18 years (2002-2019) of the U.S. National Survey on Drug Use and Health (NSDUH) among women (n = 280,626) categorized by rural-urban residence, pregnancy status, using weighted logistic regression models testing time trends and controlling for well-established sociodemographic predictors of smoking (race/ethnicity, education, income). Concerns regarding changes in survey methods used before 2002 and after 2019 precluded inclusion of earlier and more recent survey years in the present study. RESULTS: Overall smoking prevalence across years was greater in rural than urban residents (adjusted odds ratio [AOR] = 1.11; 95%CI, 1.07-1.15; P < .001) including those not-pregnant (AOR = 1.10; 1.07-1.14; P < .001) and pregnant (AOR = 1.29; 1.09-1.52; P < .001). Overall quit ratios across years were lower in rural than urban residents (AOR = 0.93; 0.87-0.99; P < .001) including those not-pregnant (AOR = 0.93; 0.88-1.00, P = .035) and pregnant (AOR = 0.78; 0.62-0.99; P = .039). Interactions of rural versus urban residence with study years for prevalence and quit ratios overall and by pregnancy status are detailed in the main text. CONCLUSIONS: These results support a longstanding and robust rural disparity in smoking prevalence among women of reproductive age including those currently pregnant and provides novel evidence that differences in smoking cessation contribute to this disparity further underscoring a need for greater access to evidence-based tobacco control and regulatory interventions in rural regions.

6.
Front Med (Lausanne) ; 11: 1390049, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841575

RESUMEN

Background: Liver fibrosis significantly impacts public health globally. Untreated liver fibrosis eventually results in cirrhosis. Cigarette smoking is the main etiologic factor for various diseases. However, the causal effects of cigarette smoking on liver fibrosis and cirrhosis have yet to be fully elucidated. Methods: In this study, Mendelian randomization (MR) analysis was performed to assess the association between cigarette smoking, liver fibrosis, and cirrhosis. Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables from a genome-wide association study (GWAS) of European ancestry. Patients were divided into six exposure categories as follows: "ever smoked," "pack years of smoking," "age of smoking initiation," "smoking status: never," "smoking status: current," and "smoking status: previous." The outcomes of this study included liver fibrosis and cirrhosis. MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode were selected as the analysis methods. Cochran's Q and the MR-PRESSO tests were conducted to measure heterogeneity. The MR-Egger method was performed to evaluate horizontal pleiotropy, while the "leave-one-out" analysis was performed for sensitivity testing. Results: The results of this study showed that having a smoking history increases the risk of liver fibrosis and cirrhosis ["ever smoked": odds ratio (OR) = 5.704, 95% CI: 1.166-27.910, p = 0.032; "smoking status: previous": OR = 99.783, 95% CI: 2.969-3.353e+03, p = 0.010]. A negative correlation was observed between patients who never smoked and liver fibrosis and cirrhosis ("smoking status: never": OR = 0.171, 95% CI: 0.041-0.719, p = 0.016). However, there were no significant associations between "smoking status: current," "pack years of smoking," and "age of smoking initiation" and liver fibrosis and cirrhosis. Cigarette smoking did not have a significant horizontal pleiotropic effect on liver fibrosis and cirrhosis. The "Leave-one-out" sensitivity analysis indicated that the results were stable. Conclusion: The study confirmed the causal effects of cigarette smoking on liver fibrosis and cirrhosis.

7.
Heliyon ; 10(11): e31865, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38845899

RESUMEN

As the malignant tumor with the highest incidence in male, prostate cancer poses a significant threat to the reproductive health of elderly men. Our previous studies have shown that promoting necroptosis of cancer cells can effectively inhibit cancer cell proliferation. This study includes lentivirus-mediated knockdown of ß2AR which resulted in stable transfectants that exhibited an increased ability to form clones compared to that of the negative control group. In the protein and mRNA levels, necroptosis associated RIP and mixed lineage kinase domain-like (MLKL) were significantly higher in the treatment group than they were in the control group. Furthermore, cells treated with propranolol exhibited necrotic morphology as observed by transmission electron microscopy. The combination of ß2AR suppression and necroptosis inhibitors resulted in a more potent suppression of cell proliferation compared to that observed in the control and negative control groups. Additionally, it elevated in the necrosis rate as determined by flow cytometry. Immunofluorescence staining revealed enhanced RIP and MLKL expression in the sh-ß2AR group compared to levels in the negative control group. Co-immunoprecipitation experiments detected an interaction between ß2AR and RIP. MLKL and RIPK3 levels were significantly higher in xenograft tumor sections from the sh-ß2AR group compared to levels in the sh-NC group. To conclude, our research indicates the proliferation of PC-3 and DU-145 cprostate cancer cells can be suppressed by inhibiting ß2AR, and this occurs through the RIP/MLKL-mediated pathway of necroptosis.

8.
FEBS J ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712529

RESUMEN

Docetaxel (Doc) currently serves as the primary first-line treatment for patients with castrate-resistant prostate cancer (CRPC). Erastin, a small molecule compound, can trigger inhibition of the cystine-glutamate reverse transport system and other pathways, leading to iron-dependent cell death (ferroptosis). Beyond its role in inducing cancer cell death, erastin demonstrates potential when combined with chemotherapy drugs to heighten cancer cell drug susceptibility. However, the augmentation by erastin of the effects of Doc treatment on prostate cancer, and the underlying mechanisms involved, remain unclear. In the present study, we determined the role and the underlying molecular mechanism of erastin against CRPC. The results showed that CRPC cell lines were resistant to Doc, and the expression of ferroptosis-related factors in drug-resistant cell lines was downregulated. Erastin, in synergy with Doc, exerts a pro-apoptotic effect. Erastin significantly inhibited the activity of ATP-binding cassette subfamily B member 1 (ABCB1) but did not change its protein expression and localization. Finally, in mice, erastin treatment dramatically reduced tumor growth in vivo. Taken together, our findings demonstrate that erastin enhances Doc-induced apoptosis to a certain extent and reverses Doc resistance in prostate cancer by inhibiting the activity of multidrug-resistant protein ABCB1.

9.
Acta Biomater ; 181: 391-401, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38704114

RESUMEN

Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K+ (BICK) with the highest transport activity among them. The selected BICK can restore potassium ion transport and increase transmembrane potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BICK does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic ion channels, such as BICK, will show great potential in treating diseases related to ion transport blockade. STATEMENT OF SIGNIFICANCE: Type 2 long QT syndrome (LQT2) is a disease caused by K+ transport disorder, which can cause malignant arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K+ transmembrane transport. In this study, we report that a small-molecule biomimetic ion channel BICK can efficiently simulate natural K+ channel proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K+ transport function for the first time. This study found that the potassium transmembrane transport by BICK significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease.


Asunto(s)
Síndrome de QT Prolongado , Potasio , Síndrome de QT Prolongado/metabolismo , Animales , Potasio/metabolismo , Cobayas , Humanos , Potenciales de Acción/efectos de los fármacos , Transporte Iónico/efectos de los fármacos , Masculino , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Canales de Potasio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Frecuencia Cardíaca/efectos de los fármacos
10.
Emerg Microbes Infect ; 13(1): 2352426, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38713582

RESUMEN

Linking identified MPOX cases to care is essential for MPOX control. This study aims to investigate the intentions of healthcare seeking and self-isolation for MPOX among men who have sex with men (MSM) in China. A cross-sectional online survey was conducted in early August 2023 in China. Respondents were recruited by community-based organizations (CBOs), collecting information on demographics, health status, behavioural and psychological characteristics. Univariate and multivariate logistic regression analyses were performed to examine the predictors of intentions to seek healthcare and self-isolate for MPOX within the MSM population. A total of 7725 participants were recruited, with a median age of 30 years. 92.21% of the participants would seek healthcare for MPOX-like symptoms, but only 52.50% intended to self-isolate if diagnosed. Intentions to seek healthcare were lower among those with MPOX-like symptoms in the past 3 months (standardized prevalence ratio (SPRs) = 0.82, 95% CI: 0.74-0.89) and the willingness to self-isolate was reduced among those diagnosed with MPOX in the past 3 months (SPRs = 0.65, 95% CI: 0.48-0.87). Participants free of sexually transmitted infections (STIs) and those aware of their HIV status were more likely to seek healthcare and self-isolate than those with STIs or unaware of their HIV status. Regular followers of MPOX information and those perceiving a low risk of infection were more inclined to take preventive measures. These findings highlight the need for targeted MPOX prevention strategies for high-risk groups and the importance of addressing barriers in infectious disease prevention response.


Asunto(s)
Homosexualidad Masculina , Intención , Aceptación de la Atención de Salud , Humanos , Masculino , Estudios Transversales , China , Adulto , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Adulto Joven , Persona de Mediana Edad , Enfermedades de Transmisión Sexual/prevención & control , Encuestas y Cuestionarios , Adolescente , Minorías Sexuales y de Género/psicología
11.
Anal Chem ; 96(21): 8325-8331, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38738931

RESUMEN

The high expression of Spermidine/spermine N1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported ß-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host-guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.


Asunto(s)
Amantadina , Nanoporos , gamma-Ciclodextrinas , gamma-Ciclodextrinas/química , Humanos , Amantadina/química , Amantadina/análisis , Neoplasias
12.
ACS Infect Dis ; 10(6): 1970-1979, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38819944

RESUMEN

Bacterial resistance caused by ß-lactamases has been a major threat to public health around the world, seriously weakening the efficacy of ß-lactam antibiotics, the most widely used therapeutic agents against infectious diseases. To detect the bacterial resistance to ß-lactam antibiotics, particularly specific type of ß-lactam antibiotics, in a rapid manner, we report herein a relay-response chemiluminescence assay. This assay mainly consists of two reagents: a ß-lactam-caged thiophenol and a thiophenol-sensitive chemiluminescence reporter, both of which are synthetically feasible. The selective hydrolysis of ß-lactam by ß-lactamase leads to the releasing of free thiophenol, which then triggers the emission of a chemiluminescence signal in a relay manner. Three thiophenol-caged ß-lactams, structural analogues of cephalothin, cefotaxime, and meropenem, respectively, have been synthesized. And the application of this assay with these analogues of ß-lactam antibiotics allows fast detection of ß-lactamase-expressing resistant bacteria and, more impressively, provides detailed information on the resistant scope of bacteria.


Asunto(s)
Antibacterianos , Mediciones Luminiscentes , Resistencia betalactámica , beta-Lactamasas , beta-Lactamas , beta-Lactamas/farmacología , Antibacterianos/farmacología , Mediciones Luminiscentes/métodos , beta-Lactamasas/metabolismo , Pruebas de Sensibilidad Microbiana , Bacterias/efectos de los fármacos , Antibióticos Betalactámicos
13.
J Med Chem ; 67(10): 8099-8121, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38722799

RESUMEN

Nicotinamide phosphoribosyltransferase (NAMPT) is an attractive therapeutic target for treating select cancers. There are two forms of NAMPT: intracellular NAMPT (iNAMPT, the rate-limiting enzyme in the mammalian NAD+ main synthetic pathway) and extracellular NAMPT (eNAMPT, a cytokine with protumorigenic function). Reported NAMPT inhibitors only inhibit iNAMPT and show potent activities in preclinical studies. Unfortunately, they failed to show efficacy due to futility and toxicity. We developed a series of FK866-based NAMPT-targeting PROTACs and identified LYP-8 as a potent and effective NAMPT degrader that simultaneously diminished iNAMPT and eNAMPT. Importantly, LYP-8 demonstrated superior efficacy and safety in mice when compared to the clinical candidate, FK866. This study highlights the importance and feasibility of applying PROTACs as a superior strategy for interfering with both the enzymatic function of NAMPT (iNAMPT) and nonenzymatic function of NAMPT (eNAMPT), which is difficult to achieve with conventional NAMPT inhibitors.


Asunto(s)
Acrilamidas , Diseño de Fármacos , Nicotinamida Fosforribosiltransferasa , Piperidinas , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Nicotinamida Fosforribosiltransferasa/metabolismo , Acrilamidas/farmacología , Acrilamidas/química , Acrilamidas/síntesis química , Animales , Humanos , Piperidinas/farmacología , Piperidinas/química , Ratones , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Citocinas/metabolismo , Línea Celular Tumoral , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/química
14.
Sleep Med ; 118: 63-70, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38613858

RESUMEN

OBJECTIVES: The study aimed to explore the underlying mechanisms of OSA-related cognitive impairment by investigating the altered topology of brain white matter networks in children with OSA. METHODS: Graph theory was used to examine white matter networks' network topological properties in 46 OSA and 31 non-OSA children. All participants underwent MRI, polysomnography, and cognitive testing. The effects of the obstructive apnea-hypopnea index (OAHI) on topological properties of white matter networks and network properties on cognition were studied using hierarchical linear regression. Mediation analyses were used to explore whether white matter network properties mediated the effects of OAHI on cognition. RESULTS: Children with OSA had significantly higher assortativity than non-OSA children. Furthermore, OAHI was associated with the nodal properties of several brain regions, primarily in the frontal and temporal lobes. The relationship between OAHI and verbal comprehension index was mediated through clustering coefficients in the right temporal pole of the superior temporal gyrus. CONCLUSIONS: OSA affects the development of white matter networks in children's brains. Besides, the mediating role of white matter network properties between the OAHI and the verbal comprehension index provided neuroimaging evidence of impaired cognitive function in children with OSA.


Asunto(s)
Imagen por Resonancia Magnética , Polisomnografía , Apnea Obstructiva del Sueño , Sustancia Blanca , Humanos , Masculino , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/complicaciones , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Femenino , Niño , Cognición/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Pruebas Neuropsicológicas/estadística & datos numéricos , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología
15.
Asian J Pharm Sci ; 19(2): 100886, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38590795

RESUMEN

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood-brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

16.
Small ; : e2311353, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38573945

RESUMEN

Atomic force microscope (AFM) videos reveal the near-surface nanostructure and dynamics of the ionic liquids (ILs) 1-butyl-3-methylimidazolium dicyanamide (BMIM DCA) and 1-hexyl-3-methylimidazolium dicyanamide (HMIM DCA) above highly oriented pyrolytic graphite (HOPG) electrodes as a function of surface potential. Molecular dynamics (MD) simulations reveal the molecular-level composition of the nanostructures. In combination, AFM and MD show that the near-surface aggregates form via solvophobic association of the cation alkyl chains at the electrode interface. The diffusion coefficients of interfacial nanostructures are ≈0.01 nm2 s-1 and vary with the cation alkyl chain length and the surface potential. For each IL, the nanostructure diffusion coefficients are similar at open-circuit potential (OCP) and OCP + 1V, but BMIM DCA moves about twice as fast as HMIM DCA. At negative potentials, the diffusion coefficient decreases for BMIM DCA and increases for HMIM DCA. When the surface potential is switched from negative to positive, a sudden change in the direction of the nanostructure motion is observed for both BMIM DCA and HMIM DCA. No transient dynamics are noted following other potential jumps. This study provides a new fundamental understanding regarding the dynamics of electrochemically stable ILs at electrodes vital for the rational development of IL-based electrochemical devices.

17.
World J Gastrointest Surg ; 16(3): 907-920, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38577086

RESUMEN

BACKGROUND: Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced (ECE) delivery of lumen-apposing metal stent (LAMS) is gradually being recognized as a viable palliative technique for malignant biliary obstruction after endoscopic retrograde cholangiopancreatography (ERCP) failure. However, most of the studies that have assessed its efficacy and safety were small and heterogeneous. Prior meta-analyses of six or fewer studies that were published 2 years ago were therefore underpowered to yield convincing evidence. AIM: To update the efficacy and safety of ECE-LAMS for treatment of biliary obstruction after ERCP failure. METHODS: We searched PubMed, EMBASE, and Scopus databases from the inception of the ECE technique to May 13, 2022. Primary outcome measure was pooled technical success rate, and secondary outcomes were pooled rates of clinical success, reintervention, and adverse events. Meta-analysis was performed using a random-effects model following Freeman-Tukey double-arcsine transformation in R software (version 4.1.3). RESULTS: Fourteen eligible studies involving 620 participants were ultimately included. The pooled rate of technical success was 96.7%, and clinical success was 91.0%. Adverse events were reported in 17.5% of patients. Overall reintervention rate was 7.3%. Subgroup analyses showed results were generally consistent. CONCLUSION: ECE-LAMS has favorable success with acceptable adverse events in relieving biliary obstruction when ERCP is impossible. The consistency of results across most subgroups suggested that this is a generalizable approach.

18.
Int Wound J ; 21(4): e14742, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38581265

RESUMEN

Echocardiographic guidance in left atrial appendage (LAA) closure procedures is increasingly recognized for its potential to enhance patient outcomes in atrial fibrillation (AF). This retrospective study assesses its impact on hospital stay duration, readmission rates and surgical site wound complications in 200 AF patients. Divided equally into an echocardiographically guided group (Group E) and a non-guided group (Group N), the analysis focused on detailed patient data encompassing hospital stay, 30-day readmission and wound complications. Findings revealed that Group E experienced a significantly shorter average hospital stay of 3.5 days, compared with 6.5 days in Group N, along with a lower 30-day readmission rate (5% vs. 18% in Group N). Furthermore, Group E showed a considerable reduction in surgical site wound complications, such as infections and hematomas. The study concludes that echocardiographic guidance in LAA closure procedures markedly improves postoperative wound outcomes, underscoring its potential as a standard practice in cardiac surgeries for AF patients. This approach not only optimizes patient safety and postoperative recovery but also enhances healthcare resource utilization.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Humanos , Estudios Retrospectivos , Cierre del Apéndice Auricular Izquierdo , Resultado del Tratamiento , Ecocardiografía , Fibrilación Atrial/cirugía , Fibrilación Atrial/complicaciones , Complicaciones Posoperatorias/prevención & control , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía
19.
Angew Chem Int Ed Engl ; 63(24): e202403203, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38590293

RESUMEN

Nanozymes have demonstrated significant potential in combating malignant tumor proliferation through catalytic therapy. However, the therapeutic effect is often limited by insufficient catalytic performance. In this study, we propose the utilization of strain engineering in metallenes to fully expose the active regions due to their ultrathin nature. Here, we present the first report on a novel tensile strain-mediated local amorphous RhRu (la-RhRu) bimetallene with exceptional intrinsic photothermal effect and photo-enhanced multiple enzyme-like activities. Through geometric phase analysis, electron diffraction profile, and X-ray diffraction, it is revealed that crystalline-amorphous heterophase boundaries can generate approximately 2 % tensile strain in the bimetallene. The ultrathin structure and in-plane strain of the bimetallene induce an amplified strain effect. Both experimental and theoretical evidence support the notion that tensile strain promotes multiple enzyme-like activities. Functioning as a tumor microenvironment (TME)-responsive nanozyme, la-RhRu exhibits remarkable therapeutic efficacy both in vitro and in vivo. This work highlights the tremendous potential of atomic-scale tensile strain engineering strategy in enhancing tumor catalytic therapy.


Asunto(s)
Terapia Fototérmica , Humanos , Catálisis , Animales , Ratones , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Resistencia a la Tracción , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos
20.
Opt Express ; 32(6): 9343-9361, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571171

RESUMEN

Many chlorophyll-a (Chl-a) remote sensing estimation algorithms have been developed for inland water, and they are proposed always based on some ideal assumptions, which are difficult to meet in complex inland waters. Based on MIE scattering theory, this study calculated the optical properties of mineral particles under different size distribution and refractive index conditions, and the Hydrolight software was employed to simulate remote sensing reflectance in the presence of different mineral particles. The findings indicated that the reflectance is significantly influenced by the slope (j) of particle size distribution function and the imaginary part (n') of the refractive index, with the real part (n) having a comparatively minor impact. Through both a simulated dataset containing 18,000 entries and an in situ measured dataset encompassing 2183 data from hundreds of lakes worldwide, the sensitivities of band ratio (BR), fluorescence baseline height (FLH), and three-band algorithms (TBA) to mineral particles were explored. It can be found that BR showed the best tolerance to mineral particles, followed by TBA. However, when the ISM concentration is less than 30 g m-3, the influence of CDOM cannot be ignored. Additionally, a dataset of over 400 entries is necessary for developing the BR algorithm to mitigate the incidental errors arising from differences in data magnitude. And if the amount of developing datasets is less than 400 but greater than 200, the TBA algorithm is more likely to obtain more stable accuracy.

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