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1.
J Cancer Res Clin Oncol ; 150(10): 480, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39465435

RESUMEN

PURPOSE: Tumor recurrence after radiofrequency ablation (RFA) affects the survival rate of patients and limits its clinical application. Tumor recurrence around the ablation area may be related to the thermal injury of hepatocytes (HCs) around the tumor, but the specific mechanism is still unclear. METHODS: A liver cancer thermal injury mouse model was established via RFA in the C57BL/6 mice. Primary HCs and Kupffer cells (KCs) were isolated and cultured to assess their sensitivity to thermal injury via the MTT assay. Flow cytometry was used to assess macrophage polarization. Furthermore, Western blotting and co-immunoprecipitation (co-IP) were utilized to evaluate the protein expression of intracellular signaling pathway. Finally, Transwell and wound healing assays was conducted to evaluate the invasion potential of liver cancer cells. RESULTS: Our findings revealed that RFA-induced liver thermal injury promoted the upregulation and secretion of HMGB1 in HCs. HMGB1 had a protective effect on HCs thermal injury, potentially mediated through autophagy regulation. Heat-injured HCs release HMGB1, which activates the TREM1/JAK2/STAT3 signaling pathway in KCs, thus fostering an immunosuppressive tumor microenvironment (TME). Moreover, HMGB1 secretion by heat-injured HCs exacerbates the migration and invasion of HCC cells by influencing macrophage polarization. CONCLUSION: RFA-induced thermal injury triggers HMGB1 release from HCs, driving macrophage M2 polarization and increasing the invasion ability of liver cancer cells. These findings reveal a potential therapeutic target for combating liver cancer recurrence following thermal ablation.


Asunto(s)
Carcinoma Hepatocelular , Proteína HMGB1 , Hepatocitos , Neoplasias Hepáticas , Ratones Endogámicos C57BL , Ablación por Radiofrecuencia , Receptor Activador Expresado en Células Mieloides 1 , Animales , Ratones , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Hepatocitos/metabolismo , Hepatocitos/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proteína HMGB1/metabolismo , Ablación por Radiofrecuencia/métodos , Ablación por Radiofrecuencia/efectos adversos , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Humanos , Masculino , Progresión de la Enfermedad , Microambiente Tumoral , Macrófagos del Hígado/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Transducción de Señal
2.
Sci Adv ; 10(42): eadp8719, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39423274

RESUMEN

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and ß-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities.


Asunto(s)
Colorantes Fluorescentes , Imagen Óptica , Colorantes Fluorescentes/química , Animales , Humanos , Imagen Óptica/métodos , Ratones , beta-Ciclodextrinas/química , Neoplasias/diagnóstico por imagen , Neoplasias/diagnóstico , Lesión Renal Aguda/diagnóstico por imagen , Lesión Renal Aguda/diagnóstico , Carbocianinas/química
3.
J Sci Food Agric ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39268777

RESUMEN

BACKGROUND: Dictyophora indusiata polysaccharide is an important bioactive component of D. indusiata, playing an important role in alleviating inflammation. The present study aimed to investigate the anti-inflammatory effect and mechanism of D. indusiata polysaccharide on lipopolysaccharide (LPS)-induced intestinal inflammation in mice. RESULTS: Our results indicated that D. indusiata polysaccharide ameliorated intestinal inflammation of mice by increasing the body weight, the number of goblet cells and decreasing inflammatory cell infiltration. In addition, D. indusiata polysaccharide significantly up-regulated expression of ZO-1, Occuldin mRNA, which were 2.55-fold and 2.28-fold higher than the LPS group, respectively. In particular, D. indusiata polysaccharide effectively inhibited the Toll-like receptor 4 (TLR4)/ c-Jun NH2-terminal kinase (JNK) signalling pathway which was 0.34-fold and 0.49-fold of gene expression and 0.41-fold and 0.39-fold of protein expression in the LPS group, respectively. CONCLUSION: The results of the present study suggested that D. indusiata polysaccharide exerted anti-inflammatory and intestinal protective effects by inhibiting the TLR4/JNK signaling pathway, which will provide a basis for the potential value of D. indusiata polysaccharide as prebiotics in food applications. © 2024 Society of Chemical Industry.

5.
Proc Natl Acad Sci U S A ; 121(33): e2403740121, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39102540

RESUMEN

The formation of macrophage-derived foam cells has been recognized as the pathological hallmark of atherosclerotic diseases. However, the pathological evolution dynamics and underlying regulatory mechanisms remain largely unknown. Herein, we introduce a single-particle rotational microrheology method for pathological staging of macrophage foaming and antiatherosclerotic explorations by probing the dynamic changes of lysosomal viscous feature over the pathological evolution progression. The principle of this method involves continuous monitoring of out-of-plane rotation-caused scattering brightness fluctuations of the gold nanorod (AuNR) probe-based microrheometer and subsequent determination of rotational relaxation time to analyze the viscous feature in macrophage lysosomes. With this method, we demonstrated the lysosomal viscous feature as a robust pathological reporter and uncovered three distinct pathological stages underlying the evolution dynamics, which are highly correlated with a pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback loop. We also validated the potential of this positive feedback loop as a promising therapeutic target and revealed the time window-dependent efficacy of NLRP3 inflammasome-targeted drugs against atherosclerotic diseases. To our knowledge, the pathological staging of macrophage foaming and the pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback mechanism have not yet been reported. These findings provide insights into in-depth understanding of evolutionary features and regulatory mechanisms of macrophage foaming, which can benefit the analysis of effective therapeutical drugs as well as the time window of drug treatment against atherosclerotic diseases in preclinical studies.


Asunto(s)
Aterosclerosis , Células Espumosas , Oro , Proteína con Dominio Pirina 3 de la Familia NLR , Aterosclerosis/patología , Animales , Oro/química , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células Espumosas/patología , Células Espumosas/metabolismo , Macrófagos/patología , Macrófagos/metabolismo , Humanos , Lisosomas/metabolismo , Inflamasomas/metabolismo , Nanotubos/química , Reología
6.
Talanta ; 279: 126606, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39089080

RESUMEN

Due to the pathogen-specific targeting, neutralization capabilities, and enduring efficacy, neutralizing antibodies (NAs) have received widespread attentions as a critical immunotherapeutic strategy against infectious viruses. However, because of the high variability and complexity of pathogens, rapid determination of neutralization activity of antiviral antibodies remains a challenge. Here, we report a new method, named as out-of-plane polarization imaging based single-particle rotational sensing, for rapid analysis of neutralization activity of antiviral antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the spike protein functionalized gold nanorods (AuNRs) and angiotensin-converting enzyme 2 (ACE2) coated gold nanoparticles (AuNPs) as the rotational sensors and chaperone probes, we demonstrated the single-particle rotational sensing strategy for the measurement of rotational diffusion coefficient of the chaperone-bound rotational sensors caused by the specific spike protein-ACE2 interactions. This enables us to measure the neutralizing activity of neutralizing antibody from the analysis of dose-dependent changes in rotational diffusion coefficient (Dr) of the rotational sensors upon the treatment of SARS-CoV-2 antibody. With this technique, we achieved the quantitative determination of neutralization activity of a commercially available SARS-CoV-2 antibody (IC50, 294.1 ng/mL) with satisfying accuracy and anti-interference ability. This simple and robust method holds the potential for rapid and accurate evaluation of neutralization activity against different pathogenic viruses.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Anticuerpos Neutralizantes , Oro , Nanopartículas del Metal , Nanotubos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Oro/química , Anticuerpos Neutralizantes/inmunología , SARS-CoV-2/inmunología , Nanopartículas del Metal/química , Humanos , Nanotubos/química , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Antivirales/farmacología , Antivirales/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Pruebas de Neutralización/métodos
7.
Front Cardiovasc Med ; 11: 1435935, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135616

RESUMEN

Insufficient ventricular unloading is a serious complication during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) that has a crucial impact on patient outcomes. The existing conservative treatment options are limited, while mechanical decompression techniques are challenging and restricted in terms of their adoption and application. Two patients with cardiogenic shock experienced insufficient left ventricular unloading with no pulsatile contraction and aortic valve closure during VA-ECMO support. Gentle chest compression was applied to establish an active left ventricular drainage mechanism, which prevented the formation of intracardiac thrombi. No life-threatening complications or technical problems occurred. Therefore, gentle chest compression was established as an effective and safe method for treating insufficient left ventricular unloading in VA-ECMO patients.

8.
Anal Chem ; 96(33): 13447-13454, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39119849

RESUMEN

Small-molecule fluorescent probes have emerged as potential tools for cancer cell imaging-based diagnostic and therapeutic applications, but their limited selectivity and poor imaging contrast hinder their broad applications. To address these problems, we present the design and construction of a novel near-infrared (NIR) biotin-conjugated and viscosity-activatable fluorescent probe, named as QL-VB, for selective recognition and imaging of cancer cells. The designed probe exhibited a NIR emission at 680 nm, with a substantial Stokes shift of 100 nm and remarkably sensitive responses toward viscosity changes in solution. Importantly, QL-VB provided an evidently enhanced signal-to-noise ratio (SNR: 6.2) for the discrimination of cancer cells/normal cells, as compared with the control probe without biotin conjugation (SNR: 1.8). Moreover, we validated the capability of QL-VB for dynamic monitoring of stimulated viscosity changes within cancer cells and employed QL-VB for distinguishing breast cancer tissues from normal tissues in live mice with improved accuracy (SNR: 2.5) in comparison with the control probe (SNR: 1.8). All these findings indicated that the cancer-targeting and viscosity-activatable NIR fluorescent probe not only enables the mechanistic investigations of mitochondrial viscosity alterations within cancer cells but also holds the potential as a robust tool for cancer cell imaging-based applications.


Asunto(s)
Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Viscosidad , Animales , Ratones , Imagen Óptica , Femenino , Rayos Infrarrojos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Línea Celular Tumoral , Biotina/química
9.
Front Psychol ; 15: 1388236, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38984285

RESUMEN

Those who teach mathematically gifted high school students play a key role in both their identification and cultivation. Teachers who teach the Mathematical Olympiad in China work long hours and teach difficult content; they are under a significant amount of work-based pressure, and that is worthy of further study. This study analyzed the sources of stress for 33 Chinese teachers who teach the Mathematical Olympiad, collected data through semi-structured in-depth interviews, and adopted a subject analysis method based on Bronfenbrenner's ecological system that considers the influences that the complexity of socio-cultural and environment have on individual emotions. It is divided into five structural or environmental systems in which human beings develop, namely the macroscopic, external, meso, micro, and chrono systems. The research results show that the greatest influences on these teachers' stress come from the mesosystem and microsystem levels, and that the key players are students and school leaders. Educational policy and culture are found to be key factors from the macrosystem. Overall, long-term stress was seen to affect both teachers' moods and their physical health. Finally, the results offered implications for education policy and school management and suggestions for the cultivation and management of mathematics teachers who teach the gifted. Limitations of the study are discussed, and directions for future research are proposed.

10.
Front Cardiovasc Med ; 11: 1409775, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015680

RESUMEN

Background: Catastrophic Antiphospholipid Syndrome (CAPS), a severe systemic autoimmune disorder, predominantly causes life-threatening multi-organ failure, with a high mortality rate. It primarily affects small vessels, seldom impacting large vessels. Notably, acute massive pulmonary embolism (PE) with bilateral atrial thrombosis is an exceptional occurrence in CAPS. Acute pulmonary embolism (PE) is a common cardiovascular disease that progresses rapidly and has a high mortality rate. Acute massive PE combined with bilateral atrial thrombosis has an even higher mortality rate. PE treatments primarily include pharmaceuticals, catheter interventions, and surgical measures, with integrated treatment strategies demonstrating promising outcomes in clinical practice. Extracorporeal membrane oxygenation (ECMO) can provide cardiopulmonary support for the treatment of high-risk PE patients and is a proven therapeutic measure. Methods: This report presents the case of a 52-year-old male admitted due to fever and sudden onset of impaired consciousness, with cardiac ultrasound and pulmonary artery CT angiography revealing an acute large-scale pulmonary embolism accompanied by bilateral atrial thrombosis, with the condition rapidly worsening and manifesting severe respiratory and circulatory failure. With ECMO support, the patient underwent a thrombectomy using an AngioJet intervention. The diagnosis of CAPS was confirmed through clinical presentation and laboratory examination, and treatment was adjusted accordingly. Results: The patient made a successful recovery and was subsequently discharged from the hospital. Conclusion: In CAPS patients, the rare instance of acute massive PE accompanied by bilateral atrial thrombosis significantly risks severe respiratory and circulatory failure, adversely affecting prognosis. Early initiation of ECMO therapy is crucial, offering a vital opportunity to address the root cause. In this case report the patient was successfully treated with an AngioJet thrombectomy supported by ECMO.

11.
Int Immunopharmacol ; 138: 112585, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38950456

RESUMEN

The mechanism of early tumor recurrence after incomplete microwave ablation (iMWA) is poorly understood. The anti-programmed cell death protein 1 (anti-PD-1) monotherapy is reported to be ineffective to prevent the progression of residual tumor resulted from iMWA. Transforming growth factor-ß (TGFß) signaling pathway plays an important role in tumorigenesis and development. We assume blocking transforming growth factor-ß receptor (TGFßR) after incomplete iMWA may synergistically enhance the effect of anti-PD-1 antibody to prevent the progression of residual tumor. We construct an iMWA model with mice harboring Hepa1-6 derived xenograft. The Tgfb1 expression and phosphorylated-Smad3 protein expression is upregulated in the residual tumor after iMWA. With the application of TGFßR inhibitor SB431542, the cell proliferation potential, the tumor growth, the mRNA expression of epithelial mesenchymal transition (EMT) markers including Cdh2, and Vim, and cancer stem cell marker Epcam, and the infiltrating Treg cells are reduced in the residual tumor tissue. In addition, iMWA combined with TGFßR blocker and anti-PD-1 antibody further decreases the cell proliferation, tumor growth, expression of EMT markers and cancer stem cell marker, and the infiltrating Treg cells in the residual tumor tissue. Blocking TGFßR may alleviate the pro-tumoral effect of tumor microenvironment thereby significantly prevents the progression of residual tumor tissue. Our study indicates that blocking TGFßR may be a novel therapeutic strategy to enhance the effect of anti-PD-1 antibody to prevent residual hepatocellular carcinoma (HCC) progression after iMWA.


Asunto(s)
Carcinoma Hepatocelular , Dioxoles , Neoplasias Hepáticas , Receptor de Muerte Celular Programada 1 , Receptores de Factores de Crecimiento Transformadores beta , Animales , Humanos , Ratones , Benzamidas/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dioxoles/farmacología , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Ratones Endogámicos BALB C , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta1/metabolismo , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Hereditas ; 161(1): 21, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978149

RESUMEN

PURPOSE: This study aims to reveal the relationship between AMIGO2 and proliferation, migration and tumorigenicity of bladder cancer, and explore the potential molecular mechanisms. METHODS: The expression level of AMIGO2 is measured by qRT-PCR and immunohistochemistry (IHC). Stable AMIGO2 knockdown cell lines T24 and 5637 were established by lentivirus transfection. Cell Counting Kit (CCK-8 assay) was produced to determine cell proliferation, flow cytometry analysis was utilized to detect cell cycle, and wound healing assay was proceeded to test migration ability of bladder cancer cells. Xenograft mouse model was established for investigating the effect of AMIGO2 on tumor formation in vivo. The RNA Sequencing technology was applied to explore the underlying mechanisms. The expression level of PPAR-γ was measured by Western Blot. RESULTS: AMIGO2 was upregulated in bladder cancer cells and tissues. Inhibited expression of AMIGO2 suppresses cell proliferation and migration. Low AMIGO2 expression inhibited tumorigenicity of 5637 in nude mice. According to RNA-Seq and bioinformatics analysis, 917 DEGs were identified. The DEGs were mainly enriched in cell-cell adhesion, peroxisome proliferators-activated receptors (PPARs) signaling pathway and some other pathways. PPAR-γ is highly expressed in bladder cancer cell lines T24 and 5637, but when AMIGO2 is knocked down in T24 and 5637, the expression level of PPAR-γ is also decreased, and overexpression of PPAR-γ could reverse the suppression effect of cell proliferation and migration caused by the inhibition of AMIGO2. CONCLUSION: AMIGO2 is overexpressed in bladder cancer cells and tissues. Knockdown of AMIGO2 suppresses bladder cancer cell proliferation and migration. These processes might be regulated by PPAR-γ signaling pathway.


Asunto(s)
Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , PPAR gamma , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Humanos , Animales , Línea Celular Tumoral , Ratones , Técnicas de Silenciamiento del Gen , Ratones Desnudos , Transducción de Señal
13.
J Sci Food Agric ; 104(14): 8879-8886, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38953304

RESUMEN

BACKGROUND: Laminaria japonica polysaccharide, which is an important bioactive substance of Laminaria japonica with anti-inflammatory and antioxidant effects. In this study, the molecular weight, functional groups and surface morphology were investigated to evaluate the digestive properties of Laminaria japonica polysaccharide before and after steam explosion. RESULTS: The results indicated that the Laminaria japonica polysaccharide entered the large intestine to be utilized by the gut microbiota after passing through the oral, gastric and small intestinal. Meanwhile, Laminaria japonica polysaccharide of steam explosion promoted the growth of beneficial bacteria Phascolarctobacterium and Intestinimonas, and increased the content of acetic, propionic and butyric acids, which was 2.29-folds, 2.60-folds and 1.63-folds higher than the control group after 48 h of fermentation. CONCLUSION: This study reveals that the effect of steam explosion pretreatment on the digestion in vitro and gut microbiota of Laminaria japonica polysaccharide will provide a basic theoretical basis for the potential application of Laminaria japonica polysaccharide as a prebiotic in the food industry. © 2024 Society of Chemical Industry.


Asunto(s)
Bacterias , Digestión , Microbioma Gastrointestinal , Laminaria , Polisacáridos , Vapor , Laminaria/química , Microbioma Gastrointestinal/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Fermentación , Animales , Humanos , Prebióticos/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/química , Algas Comestibles
14.
Orthop Surg ; 16(6): 1374-1380, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38693719

RESUMEN

OBJECTIVE: The most common causes of plantar and heel pain are plantar fasciitis and calcaneal spurs, and they often co-exist. Surgery is a recognized treatment for refractory plantar fasciitis. However, few studies have proposed treatment options for patients with metatarsophalangeal fasciitis with bone spurs. Accordingly, this study's purpose was to propose a four-step surgical regimen, and to improve the surgical outcome of plantar fasciitis with osteophytes and to establish a procedure for surgical treatment. METHODS: Retrospective analysis of 45 patients suffering from plantar fasciitis with bone spurs from 2020 to 2023. All patients underwent a four-step procedure, including plantar fascia release, calcaneal spur grinding, inflammatory tissue removal, and calcaneal burr decompression. The imaging parameters and functional scores were recorded before and after the operation. The objective evaluation included the measurement of calcaneal spur length on radiographs. Clinical evaluation included the American Orthopaedic Foot and Ankle Society (AOFAS), the Visual Analog Scale (VAS), and the Foot and Ankle Outcome Scale (FAOS). Measurement data that conformed to normal distribution were expressed as (x2 ± s), and pre-and postoperative AOFAS, FAOS, and VAS scores were compared using repeated-measures ANOVA, and preoperative and postoperative spur lengths were compared using paired t-tests. RESULTS: The 45 patients were followed up for 3 to 30 months, (17.72 ± 8.53) months, at final follow-up, the patient's AOFAS score improved from preoperative (74.93 ± 5.56) to (94.78 ± 3.98), FAOS score increased from preoperative (76.42 ± 3.37) to (96.16 ± 2.74), the VAS score decreased from (3.18 ± 0.54) to (1.07 ± 1.20) (p < 0.05), the length of spur decreased from (0.72 ± 1.81) cm to (0.23 ± 1.19) cm, and there were significant differences before and after operation (p < 0.05). CONCLUSION: The four-step surgical regimen is an appropriate and effective surgical procedure to treat plantar fasciitis with bone spurs.


Asunto(s)
Fascitis Plantar , Espolón Calcáneo , Humanos , Fascitis Plantar/cirugía , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Espolón Calcáneo/cirugía , Espolón Calcáneo/complicaciones , Anciano , Dimensión del Dolor , Descompresión Quirúrgica/métodos
15.
Anal Chem ; 96(23): 9551-9560, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38787915

RESUMEN

The discovery and identification of broad-spectrum antiviral drugs are of great significance for blocking the spread of pathogenic viruses and corresponding variants of concern. Herein, we proposed a plasmonic imaging-based strategy for assessing the efficacy of potential broad-spectrum antiviral drugs targeting the N-terminal domain of a nucleocapsid protein (NTD) and nucleic acid (NA) interactions. With NTD and NA conjugated gold nanoparticles as core and satellite nanoprobes, respectively, we found that the multivalent binding interactions could drive the formation of core-satellite nanostructures with enhanced scattering brightness due to the plasmonic coupling effect. The core-satellite assembly can be suppressed in the presence of antiviral drugs targeting the NTD-NA interactions, allowing the drug efficacy analysis by detecting the dose-dependent changes in the scattering brightness by plasmonic imaging. By quantifying the changes in the scattering brightness of plasmonic nanoprobes, we uncovered that the constructed multivalent weak interactions displayed a 500-fold enhancement in affinity as compared with the monovalent NTD-NA interactions. We demonstrated the plasmonic imaging-based strategy for evaluating the efficacy of a potential broad-spectrum drug, PJ34, that can target the NTD-NA interactions, with the IC50 as 24.35 and 14.64 µM for SARS-CoV-2 and SARS-CoV, respectively. Moreover, we discovered that ceftazidime holds the potential as a candidate drug to inhibit the NTD-NA interactions with an IC50 of 22.08 µM from molecular docking and plasmonic imaging-based drug analysis. Finally, we validated that the potential antiviral drug, 5-benzyloxygramine, which can induce the abnormal dimerization of nucleocapsid proteins, is effective for SARS-CoV-2, but not effective against SARS-CoV. All these demonstrations indicated that the plasmonic imaging-based strategy is robust and can be used as a powerful strategy for the discovery and identification of broad-spectrum drugs targeting the evolutionarily conserved viral proteins.


Asunto(s)
Antivirales , Oro , Nanopartículas del Metal , SARS-CoV-2 , Antivirales/farmacología , Antivirales/química , Oro/química , Nanopartículas del Metal/química , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/química , Humanos , Proteínas de la Nucleocápside de Coronavirus/química , Proteínas de la Nucleocápside de Coronavirus/metabolismo , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Tratamiento Farmacológico de COVID-19 , Dominios Proteicos , Fosfoproteínas
16.
Minerva Cardiol Angiol ; 72(5): 453-464, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38804624

RESUMEN

BACKGROUND: The aim of this study was using bioinformatic tools to identify hub genes in the relationship between septic cardiomyopathy (SCM) and cuproptosis and predict potential Chinese herbal drug candidates. METHODS: SCM datasets were downloaded from the gene expression omnibus. Cuproptosis related genes were collected from a research published on Science in March, 2022. The expression profiles of genes related to cuproptosis in SCM were extracted. Differentially expressed genes (DEGs) were analyzed using R package limma. A single-sample gene set enrichment analysis was conducted to measure the correlation between DEGs and immune cell infiltration. Hub genes were screened out by random forest model. Finally, HERB database and COREMINE database were used to predict Chinese herbal drugs for hub genes and carry out molecular docking. RESULTS: A total of 9 DEGs were identified. Cuproptosis differential genes PDHB, DLAT, DLD, FDX1, GCSH, LIAS were significantly correlated with one or more cells and their functions in immune infiltration. The random forest model screened pyruvate dehydrogenase E1 beta subunit (PDHB) as the hub gene. PDHB was negatively correlated with Plasmacytoid dendritic cell infiltration. Pyruvic acid, rhodioloside and adenosine were predicted with PDHB as the target, and all three components are able to bind to PDHB. CONCLUSIONS: Cuproptosis related gene PDHB is associated with the occurrence and immune infiltration of septic cardiomyopathy. Rhodioloside and other Chinese herbal drugs may play a role in the treatment of SCM by regulating the expression of PDHB.


Asunto(s)
Cardiomiopatías , Biología Computacional , Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Cardiomiopatías/genética , Cardiomiopatías/tratamiento farmacológico , Humanos , Simulación del Acoplamiento Molecular , Sepsis/genética , Sepsis/tratamiento farmacológico , Bases de Datos Genéticas , Perfilación de la Expresión Génica
17.
PLoS One ; 19(4): e0298109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38573999

RESUMEN

Pharmacy Intravenous Admixture Services (PIVAS) are places dedicated to the centralized dispensing of intravenous drugs, usually managed and operated by professional pharmacists and pharmacy technicians, and are an integral part of modern healthcare. However, the workflow of PIVAS has some problems, such as low efficiency and error-prone. This study aims to improve the efficiency of drug dispensing, reduce the rate of manual misjudgment, and minimize drug errors by conducting an in-depth study of the entire workflow of PIVAS and applying image recognition technology to the drug checking and dispensing process. Firstly, through experimental comparison, a target detection model suitable for drug category recognition is selected in the drug-checking process of PIVAS, and it is improved to improve the recognition accuracy and speed of intravenous drug categories. Secondly, a corner detection model for drug dosage recognition was studied in the drug dispensing stage to further increase drug dispensing accuracy. Then the PIVAS drug category recognition system and PIVAS drug dosage recognition system were designed and implemented.


Asunto(s)
Servicios Farmacéuticos , Farmacias , Servicio de Farmacia en Hospital , Farmacia , Humanos , Errores de Medicación/prevención & control , Farmacéuticos , Servicio de Farmacia en Hospital/métodos
18.
Cardiovasc Intervent Radiol ; 47(5): 592-603, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38605220

RESUMEN

PURPOSE: This study aims to evaluate the prognostic value of controlling nutritional status (CONUT) score in determining the prognosis of patients with hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (cTACE). METHODS: This study retrospectively analyzed 936 patients who underwent cTACE for HCC between January 2012 and December 2018, and divided them into two groups based on their CONUT score. To balance the bias in baseline characteristics, propensity score matched (PSM) analysis was conducted. The Kaplan-Meier method was used to establish a cumulative survival curve, and the log-rank test was employed to determine differences in overall survival (OS) and progression-free survival (PFS) among the CONUT score groups. Furthermore, the Cox proportional hazard model was employed to assess the correlation between CONUT score and OS and PFS, whereby hazard ratios (HRs) and 95% confidence intervals (95% CIs) were computed. RESULTS: Before PSM, the median OS for the low (≤ 3) and high (≥ 4) CONUT group (558 vs. 378 patients) was 21.7 and 15.6 months, respectively, and the median PFS was 5.7 and 5 months. Following PSM, both the low and high CONUT score groups comprised 142 patients. The low CONUT score group exhibited a significantly longer OS compared to the high CONUT score group, as determined by the log-rank test (median OS 22.2 vs. 17.0 months, P = 0.014). No significant association was observed between CONUT group and PFS (median PFS 6.4 vs. 4.7 months, log-rank test, P = 0.121). Cox proportional hazard regression analysis revealed that a CONUT score of ≥ 4 was an independent risk factor for OS in patients with HCC who underwent cTACE (HR = 1.361; 95% CI: 1.047-1.771; P = 0.022). These findings were consistent across most subgroup analyses. CONCLUSION: A high CONUT score has been found to be a prognostic factor for poorer OS in patients with HCC who underwent cTACE. LEVEL OF EVIDENCE: Level 3, Non-randomized controlled cohort.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Estado Nutricional , Puntaje de Propensión , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Femenino , Quimioembolización Terapéutica/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Pronóstico , Tasa de Supervivencia
19.
J Foot Ankle Surg ; 63(5): 521-525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38679411

RESUMEN

The present study was to determine the characteristics of the ankle skeletal structure in patients with talus Hepple V type. We conducted a retrospective study on the skeletal structure of the talus in 110 patients with Hepple V osteochondral lesions of the talus and in control participants. The radiographic measurements taken include the following: in the coronal plane - depth of talus frontal curvature, length of the lateral and medial malleolus; in the sagittal plane - radius and height of talus, angle of tibial lateral surface, tibiotalar sector, and vertical neck angle. The osteochondral lesion of the talus showed a significantly larger mean radius (mean ± SD, 21.4 ± 2.5 mm; p < .001) and height (mean ± SD, 26.0 ± 2.7 mm; p < .005). It also demonstrated a longer mean medial malleolus length (mean ± SD, 15.7 ± 2.4 mm; p < .005), a larger mean vertical neck angle (mean ± SD, 86.2 ± 5.4°; p < .050), and a greater mean tibial lateral surface angle (mean ± SD, 80.0 ± 4.5°; p < .001). And there was a greater mean frontal curvature depth (mean ± SD, 3.9 ± 0.6 mm; p < .005). Overall, this study found that patients with Hepple V osteochondral lesions of the talus had a larger vertical neck angle and tibial lateral surface angle, a longer talus radius and medial malleolus length, a higher talus height, and a deeper frontal curvature depth. STUDY DESIGNS: Retrospective Case-Control Study.


Asunto(s)
Astrágalo , Humanos , Astrágalo/diagnóstico por imagen , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Articulación del Tobillo/diagnóstico por imagen , Estudios de Casos y Controles , Adolescente , Radiografía
20.
J Geriatr Cardiol ; 21(1): 64-80, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38440342

RESUMEN

BACKGROUND: Left ventricular (LV) remodeling and diastolic function in people with heart failure (HF) are correlated with iron status; however, the causality is uncertain. This Mendelian randomization (MR) study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population. METHODS: Transferrin saturation (TSAT), total iron binding capacity (TIBC), and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies. Individuals without myocardial infarction history, HF, or LV ejection fraction (LVEF) < 50% (n = 16,923) in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset. The dataset included LV end-diastolic volume, LV end-systolic volume, LV mass (LVM), and LVM-to-end-diastolic volume ratio (LVMVR). We used a two-sample bidirectional MR study with inverse variance weighting (IVW) as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results. RESULTS: In the IVW analysis, one standard deviation (SD) increased in TSAT significantly correlated with decreased LVMVR (ß = -0.1365; 95% confidence interval [CI]: -0.2092 to -0.0638; P = 0.0002) after Bonferroni adjustment. Conversely, no significant relationships were observed between other iron and LV parameters. After Bonferroni correction, reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT (ß = -0.0699; 95% CI: -0.1087 to -0.0311; P = 0.0004). No heterogeneity or pleiotropic effects evidence was observed in the analysis. CONCLUSIONS: We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

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