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1.
Plant J ; 118(2): 534-548, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38230828

RESUMEN

Citrus bacterial canker (CBC) is a serious bacterial disease caused by Xanthomonas citri subsp. citri (Xcc) that adversely impacts the global citrus industry. In a previous study, we demonstrated that overexpression of an Xcc-inducible apetala 2/ethylene response factor encoded by Citrus sinensis, CsAP2-09, enhances CBC resistance. The mechanism responsible for this effect, however, is not known. In the present study, we showed that CsAP2-09 targeted the promoter of the Xcc-inducible WRKY transcription factor coding gene CsWRKY25 directly, activating its transcription. CsWRKY25 was found to localize to the nucleus and to activate transcriptional activity. Plants overexpressing CsWRKY25 were more resistant to CBC and showed higher expression of the respiratory burst oxidase homolog (RBOH) CsRBOH2, in addition to exhibiting increased RBOH activity. Transient overexpression assays in citrus confirmed that CsWRKY25 and CsRBOH2 participated in the generation of reactive oxygen species (ROS) bursts, which were able to restore the ROS degradation caused by CsAP2-09 knockdown. Moreover, CsWRKY25 was found to bind directly to W-box elements within the CsRBOH2 promoter. Notably, CsRBOH2 knockdown had been reported previously to reduce the CBC resistance, while demonstrated in this study, CsRBOH2 transient overexpression can enhance the CBC resistance. Overall, our results outline a pathway through which CsAP2-09-CsWRKY25 transcriptionally reprograms CsRBOH2-mediated ROS homeostasis in a manner conducive to CBC resistance. These data offer new insight into the mechanisms and regulatory pathways through which CsAP2-09 regulates CBC resistance, highlighting its potential utility as a target for the breeding of CBC-resistant citrus varieties.


Asunto(s)
Citrus sinensis , Citrus , Xanthomonas , Citrus/genética , Citrus/microbiología , Especies Reactivas de Oxígeno , Xanthomonas/genética , Fitomejoramiento , Citrus sinensis/genética , Citrus sinensis/microbiología , Homeostasis , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología
2.
Crit Rev Immunol ; 44(4): 23-39, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38505919

RESUMEN

Enhancer of zeste homolog 2 (EZH2)gene has a prognostic role in hepatocellular carcinoma (HCC). This study aimed to identify the role of microRNAs (miRNAs) let-7c-5p by targeting EZH2 in HCC. We downloaded gene and miRNA RNA-seq data from The Cancer Genome Atlas (TCGA) database. Differences in EZH2 expression between different groups were analyzed and the association of EZH2 expression with HCC prognosis was detected using Cox regression analysis. The miRNA-EZH2-pathway network was constructed. Dual-luciferase reporter assay was performed to detect the hsa-let-7c-5p-EZH2. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8, Wound healing, Transwell, and Flow cytometry, respectively. RT-qPCR and Western blot were used to detect the expression of let-7c-5p and EZH2. EZH2 was upregulated in HCC tumors (P < 0.0001). Cox regression analysis showed that TCGA HCC patients with high EZH2 expression levels showed a short survival time [hazard ratio (HR) = 1.677, 95% confidence interval (CI) 1.316-2.137; P < 0.0001]. Seven miRNAs were negatively correlated with EZH2 expression and were significantly downregulated in HCC tumor samples (P < 0.0001), in which hsa-let-7c-5p was associated with prognosis in HCC (HR = 0.849 95% CI 0.739-0.975; P = 0.021). We identified 14 immune cells that showed significant differences in EZH2 high- and low-expression groups. Additionally, let-7c-5p inhibited HCC cell proliferation, migration, and invasion and reversed the promoted effects of EZH2 on HCC cell malignant characteristics. hsa-let-7c-5p-EZH2 significantly suppressed HCC malignant characteristics, which can be used for HCC prognosis.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/farmacología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/genética , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica
3.
Prostate ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263692

RESUMEN

PURPOSE: This study was to construct a nomogram utilizing shear wave elastography and assess its efficacy in detecting clinically significant prostate cancer (csPCa). METHODS: 290 elderly people with suspected PCa who received prostate biopsy and shear wave elastography (SWE) imaging were respectively registered from April 2022 to December 2023. The elderly participants were stratified into two groups: those with csPCa and those without csPCa, which encompassed cases of clinically insignificant prostate cancer (cisPCa) and non-prostate cancer tissue, as determined by pathology findings. The LASSO algorithm, known as the least absolute shrinkage and selection operator, was utilized to identify features. Logistic regression analysis was utilized to establish models. Receiver operating characteristic (ROC) and calibration curves were utilized to evaluate the discriminatory ability of the nomogram. Bootstrap (1000 bootstrap iterations) was employed for internal validation and comparison with two models. A decision curve and a clinical impact curve were employed to assess the clinical usefulness. RESULTS: Our nomogram, which contained Emean, ΔEmean, prostate volume, prostate-specific antigen density (PSAD), and transrectal ultrasound (TRUS), showed better discrimination (AUC = 0.89; 95% CI: 0.83-0.94), compared to the clinical model without SWE parameters (p = 0.0007). Its accuracy, sensitivity and specificity were 0.83, 0.89 and 0.78, respectively. Based on the analysis of decision curve, the thresholds ranged from 5% to 90%. According to our nomogram, biopsying patients at a 20% probability threshold resulted in a 25% reduction in biopsies without missing any csPCa. The clinical impact curve demonstrated that the nomogram's predicted outcome is closer to the observed outcome when the probability threshold reaches 20% or greater. CONCLUSION: Our nomogram demonstrates efficacy in identifying elderly individuals with clinically significant prostate cancer, thereby facilitating informed clinical decision-making based on diagnostic outcomes and potential clinical benefits.

4.
Anal Chem ; 96(1): 437-445, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38150621

RESUMEN

Damage of reactive oxygen species to various molecules such as DNA has been related to many chronic and degenerative human diseases, aging, and even cancer. 8-Oxo-7,8-dihydroguanine (OG), the most significant oxidation product of guanine (G), has become a biomarker of oxidative stress as well as gene regulation. The positive effect of OG in activating transcription and the negative effect in inducing mutation are a double-edged sword; thus, site-specific quantification is helpful to quickly reveal the functional mechanism of OG at hotspots. Due to the possible biological effects of OG at extremely low abundance in the genome, the monitoring of OG is vulnerable to signal interference from a large amount of G. Herein, based on rolling circle amplification-induced G-triplex formation and Thioflavin T fluorescence enhancement, an ultrasensitive strategy for locus-specific OG quantification was constructed. Owing to the difference in the hydrogen-bonding pattern between OG and G, the nonspecific background signal of G sites was completely suppressed through enzymatic ligation of DNA probes and the triggered specificity of rolling circle amplification. After the signal amplification strategy was optimized, the high detection sensitivity of OG sites with an ultralow detection limit of 0.18 amol was achieved. Under the interference of G sites, as little as 0.05% of OG-containing DNA was first distinguished. This method was further used for qualitative and quantitative monitoring of locus-specific OG in genomic DNA under oxidative stress and identification of key OG sites with biological function.


Asunto(s)
ADN , Guanina , Humanos , ADN/genética , Estrés Oxidativo , Especies Reactivas de Oxígeno , Técnicas de Amplificación de Ácido Nucleico
5.
Small ; : e2402538, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770748

RESUMEN

Solving the problem of oil and water pollution is an important topic in environmental protection. The separation of oil-water emulsion with high efficiency and low consumption has been the direction of social efforts. Membrane separation technology combined with surface wettability and pore size screening is considered to be one of the most promising ways to separate oil-water emulsions. In this paper, the polyvinylidene difluoride (PVDF) membrane is prepared by combining the two methods of blending and coating modification as a double barrier. The prepared PVDF membrane can completely wet water, achieve superhydrophilic in air, and superoleophobic underwater. The separation efficiency and flux are 99.57% and 678 L h-1 m-2 bar-1, respectively, for toluene emulsions containing surfactants with an average particle size of 1.7 µm. At the same time, it can also effectively separate different kinds of light/heavy oils. After three cycles of testing still maintain high efficiency of separation. The results show that the prepared PVDF membrane can effectively separate the emulsion containing surfactant with smaller particle size distribution of oil droplets. This method provides a new strategy for the separation of oil-water emulsions and has broad application prospects.

6.
Metab Eng ; 81: 182-196, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38103887

RESUMEN

Anthocyanins are widely distributed pigments in flowering plants with red, purple or blue colours. Their properties in promoting heath make anthocyanins perfect natural colourants for food additives. However, anthocyanins with strong colour and stability at neutral pH, suitable as food colourants are relatively rare in nature. Acylation increases anthocyanin stability and confers bluer colour. In this study, we isolated two anthocyanin regulators SbMyb75 and SbDel from S. baicalensis, and showed that constitutive expression of the two TFs led to accumulation of anthocyanins at high levels in black carrot hairy roots. However, these hairy roots had severe growth problems. We then developed a ß-estradiol inducible system using XVE and a Lex-35S promoter, to initiate expression of the anthocyanin regulators and induced this system in hairy roots of black carrot, tobacco and morning glory. Anthocyanins with various decorations were produced in these hairy roots without any accompanying side-effects on growth. We further produced highly acylated anthocyanins with blue colour in a 5 L liquid culture in a bioreactor of hairy roots from morning glory. We provide here a strategy to produce highly decorated anthocyanins without the need for additional engineering of any of the genes encoding decorating enzymes. This strategy could be transferred to other species, with considerable potential for natural colourant production for the food industries.


Asunto(s)
Antocianinas , Nicotiana , Antocianinas/genética , Nicotiana/genética , Reactores Biológicos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/genética
7.
Opt Express ; 32(8): 13720-13732, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859334

RESUMEN

In this paper, we propose and demonstrate enhanced orthogonal frequency division multiplexing with index modulation (OFDM-IM) schemes for bandlimited underwater visible light communication (UVLC) systems via geometric constellation shaping (GCS) and subblock interleaving. Specifically, two heuristic GCS approaches based on particle swarm optimization (PSO) and hybrid genetic algorithm-PSO (GA-PSO) algorithms are proposed to generate IM-preferable constellations. Moreover, a generalized interleaving technique is further proposed to overcome the low-pass effect of bandlimited UVLC systems, where an optimal step size can be obtained to perform subblock interleaving. Simulation and experiments are conducted to evaluate the performance of the proposed enhanced OFDM-IM schemes in bandlimited UVLC systems, where both OFDM with single-mode index modulation (OFDM-SM) and OFDM with dual-mode index modulation (OFDM-DM) schemes are considered. The experimental results demonstrate remarkable signal-to-noise ratio (SNR) gains of 1.3 and 1.9 dB for OFDM-SM and OFDM-DM in comparison to the benchmark schemes, respectively.

8.
J Exp Bot ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38820225

RESUMEN

Citrus bacterial canker (CBC) is a disease that poses a major threat to global citrus production and is caused by infection with Xanthomonas citri subsp. citri (Xcc). Wall-associated receptor-like kinase (WAKL) proteins play an important role in shaping plant resistance to various bacterial and fungal pathogens. In a prior report, CsWAKL01 was identified as a candidate Xcc-inducible gene found to be upregulated in CBC-resistant citrus plants. However, the functional role of CsWAKL01 and the mechanisms whereby it may influence resistance to CBC have yet to be clarified. Here, CsWAKL01 was found to localize to the plasma membrane, and the overexpression of the corresponding gene in transgenic sweet oranges resulted in the pronounced enhancement of CBC resistance, whereas its knockdown had the opposite effect. Mechanistically, the ability of CsWAKL01 was linked to its ability to reprogram jasmonic acid, salicylic acid, and abscisic acid signaling activity. CsWRKY53 was further identified as a transcription factor capable of directly binding the CsWAKL01 promoter and inducing its transcriptional upregulation. CsWRKY53 silencing conferred greater CBC susceptibility to infected plants. Overall, these data support a model wherein CsWRKY53 functions as a positive regulator of CsWAKL01 to enhance resistance to CBC via the reprogramming of phytohormone signaling. Together these results offer new insight into the mechanisms whereby WAKLs shape phytopathogen resistance while underscoring the potential value of targeting the CsWRKY53-CsWAKL01 axis when seeking to breed CBC-resistant citrus plant varieties.

9.
Opt Lett ; 49(2): 334-337, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38194562

RESUMEN

In this Letter, we propose and demonstrate a dual-mode spatial index modulation (DM-SIM) scheme for spectral efficiency enhancement of band-limited multiple-input multiple-output optical wireless communication (MIMO-OWC) systems. By performing dual-mode index modulation in the spatial domain, DM-SIM can transmit both spatial and constellation symbols. Since constellation design plays a vital role in the proposed DM-SIM scheme, we further propose three dual-mode constellation design approaches including phase rotation, amplitude scaling and joint phase rotation and amplitude scaling. Moreover, we also designed a differential log-likelihood ratio (LLR) detector for the proposed DM-SIM scheme. Experimental results show that the joint phase rotation and amplitude scaling approach can achieve a remarkable 3.2 dB signal-to-noise ratio (SNR) gain compared with the phase rotation approach in a 2×2 MIMO-OWC system applying DM-SIM.

10.
Inflamm Res ; 73(9): 1445-1458, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38896288

RESUMEN

BACKGROUND: Macrophage-mediated cleaning up of dead cells is a crucial determinant in reducing coronary artery inflammation and maintaining vascular homeostasis. However, this process also leads to programmed death of macrophages. So far, the role of macrophage death in the progression of atherosclerosis remains controversial. Also, the underlying mechanism by which transcriptional regulation and reprogramming triggered by macrophage death pathways lead to changes in vascular inflammation and remodeling are still largely unknown. TRIM25-mediated RIG-I signaling plays a key role in regulation of macrophages fate, however the role of TRIM25 in macrophage death-mediated atherosclerotic progression remains unclear. This study aims to investigate the relationship between TRIM25 and macrophage death in atherosclerosis. METHODS: A total of 34 blood samples of patients with coronary stent implantation, including chronic total occlusion (CTO) leisions (n = 14) or with more than 50% stenosis of a coronary artery but without CTO leisions (n = 20), were collected, and the serum level of TRIM25 was detected by ELISA. Apoe-/- mice with or without TRIM25 gene deletion were fed with the high-fat diet (HFD) for 12 weeks and the plaque areas, necrotic core size, aortic fibrosis and inflammation were investigated. TRIM25 wild-type and deficient macrophages were isolated, cultured and stimulated with ox-LDL, RNA-seq, real-time PCR, western blot and FACS experiments were used to screen and validate signaling pathways caused by TRIM25 deletion. RESULTS: Downregulation of TRIM25 was observed in circulating blood of CTO patients and also in HFD-induced mouse aortas. After HFD for 12 weeks, TRIM25-/-ApoeE-/- mice developed smaller atherosclerotic plaques, less inflammation, lower collagen content and aortic fibrosis compared with TRIM25+/+ApoeE-/- mice. By RNA-seq and KEGG enrichment analysis, we revealed that deletion of TRIM25 mainly affected pyroptosis and necroptosis pathways in ox-LDL-induced macrophages, and the expressions of PARP1 and RIPK3, were significantly decreased in TRIM25 deficient macrophages. Overexpression of TRIM25 promoted M1 polarization and necroptosis of macrophages, while inhibition of PARP1 reversed this process. Further, we observed that XRCC1, a repairer of DNA damage, was significantly upregulated in TRIM25 deficient macrophages, inhibiting PARP1 activity and PARP1-mediated pro-inflammatory change, M1 polarization and necroptosis of macrophages. By contrast, TRIM25 overexpression mediated ubiquitination of XRCC1, and the inhibition of XRCC1 released PARP1, and activated macrophage M1 polarization and necroptosis, which accelerated aortic inflammation and atherosclerotic plaque progression. CONCLUSIONS: Our study has uncovered a crucial role of the TRIM25-XRCC1Ub-PARP1-RIPK3 axis in regulating macrophage death during atherosclerosis, and we highlight the potential therapeutic significance of macrophage reprogramming regulation in preventing the development of atherosclerosis.


Asunto(s)
Aterosclerosis , Macrófagos , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Ubiquitinación , Animales , Humanos , Masculino , Ratones , Persona de Mediana Edad , Apoptosis , Aterosclerosis/patología , Aterosclerosis/metabolismo , Aterosclerosis/genética , Dieta Alta en Grasa , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
11.
J Cardiovasc Pharmacol ; 84(3): 331-339, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39240728

RESUMEN

ABSTRACT: In this study, we investigated the safety and efficacy of fondaparinux sodium in postpercutaneous coronary intervention (PCI) anticoagulation therapy for patients with ST-segment elevation myocardial infarction. There are a total of 200 patients with ST segment elevation myocardial infarction underwent PCI and anticoagulation therapy. They were randomly split into experimental (n = 108) and control groups (n = 92). The experimental group received postoperative fondaparinux sodium (2.5 mg q.d), while the control group received enoxaparin (4000 IU q12 h). We did not use a loading dose for enoxaparin. Bleeding incidence and major adverse cardiovascular/cerebrovascular events were monitored during hospitalization, and at 1, 3, and 6 months postsurgery. The primary end points, including bleeding, mortality, and myocardial infarction during hospitalization, were not significantly different between the 2 groups. For secondary end points, the incidence of combined end point events at 1 month, 3 months, and 6 months after surgery in the experimental group was lower than in the control group (P < 0.05). According to Cox regression analysis, the risk of bleeding in the experimental group was significantly lower than that in the control group [hazard ratios: 0.506, 95% confidence interval (CI): 0.284-0.900] (P = 0.020). The risk of mortality in the experimental group was significantly lower than in the control group (hazard ratio: 0.188, 95% CI: 0.040-0.889) (P = 0.035). In summary, perioperative use of fondaparinux sodium during PCI in patients with STEMI in this study was associated with a lower risk of bleeding and death compared with enoxaparin use in the absence of loading dose.


Asunto(s)
Enoxaparina , Fondaparinux , Hemorragia , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Fondaparinux/uso terapéutico , Fondaparinux/efectos adversos , Fondaparinux/administración & dosificación , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/diagnóstico , China/epidemiología , Resultado del Tratamiento , Hemorragia/inducido químicamente , Enoxaparina/efectos adversos , Enoxaparina/administración & dosificación , Enoxaparina/uso terapéutico , Factores de Riesgo , Factores de Tiempo , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/uso terapéutico , Estudios Prospectivos
12.
BMC Gastroenterol ; 24(1): 265, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143462

RESUMEN

BACKGROUND: The activity and number of immune cells in the tumor microenvironment are closely related to the overall survival of patients with hepatocellular carcinoma (HCC). The sex-determining region Y-box 4 (SOX4) gene is abnormally expressed in various tumor tissues and is critical for tumor development. However, the correlation between SOX4 expression in HCC and tumor immunity is unclear. METHODS: SOX4 expression was explored using data from The Cancer Genome Atlas, and UALCAN databases. Real-time reverse transcription quantitative and western blotting were used to analyze SOX4 expression in several liver cancer cell lines. Additionally, correlations among SOX4 expression, cancer immune characteristics, and infiltrated immune cell gene marker sets in patients with HCC were analyzed using data from the Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions databases. Moreover, we evaluated SOX4 expression in HCC tissues and the correlation of SOX4 expression with survival rate. Subsequently, noncoding RNAs (ncRNAs) responsible for SOX4 overexpression were identified using expression, correlation, and survival analyses. RESULTS: SOX4 expression was significantly upregulated in HCC and correlated with a poor prognosis. Additionally, SOX4 upregulation in HCC positively correlated with immune cell infiltration, several biomarkers of immune cells, and immune checkpoint expression. Finally, the MCM3AP-AS1/hsa-miR-204-5p axis was identified as the most likely upstream ncRNA-related pathway for SOX4 in HCC. These results indicated that ncRNA-mediated upregulation of SOX4 correlated with the immune infiltration level and poor prognosis in HCC. Our findings provide new directions for the development of novel immunotherapeutic targets for HCC.


Asunto(s)
Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Factores de Transcripción SOXC , Regulación hacia Arriba , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Pronóstico , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , ARN no Traducido/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Masculino , Femenino , Tasa de Supervivencia
13.
BMC Cardiovasc Disord ; 24(1): 43, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38218809

RESUMEN

BACKGROUND: Cardiac masses can encompass a variety of conditions, such as tumors, thrombi, vegetations, calcific lesions, and other rare diseases. Treatment and management of these types of cardiac masses differ considerably. Thus, accurately distinguishing among thrombi, benign tumors, and malignant tumors in the heart is of great importance. Contrast echocardiography (CE) has emerged as a promising technology. Although published guidelines suggest that CE can enhance image quality and assist in differentiating between benign and malignant lesions, most studies on CE diagnosis of cardiac masses are limited to case reports or retrospective/small-sample-sized prospective cohorts. This study aims to evaluate the diagnostic accuracy of CE in patients with suspected cardiac masses and address the insufficient evidence for differential diagnosis using CE. METHODS: Between April 2018 and July 2022, a prospective multicenter study was conducted, which included 145 consecutive patients suspected to have cardiac masses based on transthoracic echocardiography. All patients underwent CE examinations. The echocardiographic diagnosis relied on qualitative factors such as echogenicity, boundary, morphology of the base, mass perfusion, pericardial effusion, and motility as well as quantitative factors such as the area of the masses and the peak intensity ratio of the masses to adjacent myocardium (A1/A2). RESULTS: The final confirmed diagnoses were as follows: 2 patients had no cardiac mass, 4 patients had pseudomass, 43 patients had thrombus, 66 patients had benign tumors, and 30 patients had malignant tumors. The receiver operating characteristic (ROC) analysis indicated that an optimal A1/A2 cutoff value of 0.499 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.977, 97.9%, 90.7%, 95.9%, and 95.1%, respectively. The optimal A1/A2 cutoff value of 1.583 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.950, 93.3%, 93.9%, 87.5%, and 96.9%, respectively. CONCLUSIONS: Combined with qualitative and quantitative analyses, CE has the potential to accurately differentiate among different types of cardiac masses.


Asunto(s)
Neoplasias Cardíacas , Trombosis , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Medios de Contraste , Ecocardiografía/métodos , Neoplasias Cardíacas/diagnóstico por imagen , Diagnóstico Diferencial , Sensibilidad y Especificidad
14.
Acta Pharmacol Sin ; 45(5): 926-944, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38286832

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.


Asunto(s)
Esclerosis Amiotrófica Lateral , Astrocitos , Loratadina , Loratadina/análogos & derivados , Ratones Transgénicos , Médula Espinal , Superóxido Dismutasa-1 , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Médula Espinal/metabolismo , Ratones , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Loratadina/farmacología , Loratadina/uso terapéutico , Humanos , Receptor de Serotonina 5-HT2A/metabolismo , Modelos Animales de Enfermedad , Masculino , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/uso terapéutico , Ratones Endogámicos C57BL
15.
Mol Ther ; 31(5): 1437-1450, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35982620

RESUMEN

Tubular epithelial cells (TECs) exposed to hypoxia incite tubulointerstitial inflammation (TII), while the exact mechanism is unclear. In this study, we identified that hypoxia evoked tubule injury as evidenced by tubular hypoxia-inducible factor-1α and kidney injury molecule-1 (KIM-1) expression and that renal small extracellular vesicle (sEV) production was increased with the development of TII after ischemia-reperfusion injury (IRI). Intriguingly, KIM-1-positive tubules were surrounded by macrophages and co-localized with sEVs. In vitro, KIM-1 expression and sEV release were increased in hypoxic TECs and the hypoxia-induced inflammatory response was ameliorated when KIM-1 or Rab27a, a master regulator of sEV secretion, was silenced. Furthermore, KIM-1 was identified to mediate hypoxic TEC-derived sEV (Hypo-sEV) uptake by TECs. Phosphatidylserine (PS), a ligand of KIM-1, was present in Hypo-sEVs as detected by nanoflow cytometry. Correspondingly, the inflammatory response induced by exogenous Hypo-sEVs was attenuated when KIM-1 was knocked down. In vivo, exogenous-applied Hypo-sEVs localized to KIM-1-positive tubules and exacerbated TII in IRI mice. Our study demonstrated that KIM-1 expressed by injured tubules mediated sEV uptake via recognizing PS, which participated in the amplification of tubule inflammation induced by hypoxia, leading to the development of TII in ischemic acute kidney injury.


Asunto(s)
Vesículas Extracelulares , Daño por Reperfusión , Animales , Ratones , Células Epiteliales/metabolismo , Vesículas Extracelulares/metabolismo , Hipoxia/metabolismo , Inflamación/metabolismo , Riñón/metabolismo , Daño por Reperfusión/metabolismo
16.
Genomics ; 115(5): 110667, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37315873

RESUMEN

Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Genes Supresores de Tumor , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , MicroARNs/genética , Movimiento Celular/genética , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Receptores Depuradores de Clase A/genética , Receptores Depuradores de Clase A/metabolismo
17.
Int Heart J ; 65(4): 775-777, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39010225

RESUMEN

Dextrocardia is a very rare congenital malposition, and most cardiologists are not familiar with the radiographic angiograms of this condition. Here, we first report a case of dextrocardia with a chronic total occlusion (CTO) lesion undergoing retrograde percutaneous coronary intervention (PCI). Significant difficulties in lesion interpretation and device manipulation were encountered with the original angiograms. These challenges were not significantly improved until we adopted the double-inversion technique. The procedure was finally accomplished by using the kissing wire technique with a poor angle of attack. Retrograde CTO PCI for patients with dextrocardia is feasible with adequate techniques.


Asunto(s)
Angiografía Coronaria , Oclusión Coronaria , Dextrocardia , Intervención Coronaria Percutánea , Humanos , Dextrocardia/complicaciones , Dextrocardia/diagnóstico por imagen , Intervención Coronaria Percutánea/métodos , Oclusión Coronaria/cirugía , Oclusión Coronaria/diagnóstico , Oclusión Coronaria/complicaciones , Masculino , Enfermedad Crónica , Anciano , Persona de Mediana Edad
18.
J Sci Food Agric ; 104(12): 7335-7346, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38651728

RESUMEN

BACKGROUND: The present study investigated the structure, functional and physicochemical properties of lotus seed protein (LSP) under different pH environments. The structures of LSP were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy (FTIR), zeta potential, particle size distributions, free sulfhydryl and rheological properties. The functional and physicochemical properties of LSP were characterized by color, foaming property, emulsification property, solubility, oil holding capacity, water holding capacity, differential scanning calorimetry analysis and surface hydrophobicity. RESULTS: LSP was mainly composed of eight subunits (18, 25, 31, 47, 51, 56, 65 and 151 kDa), in which the richest band was 25 kDa. FTIR results showed that LSP had high total contents of α-helix and ß-sheet (44.81-46.85%) in acidic environments. Meanwhile, there was more ß-structure and random structure in neutral and alkaline environments (pH 7.0 and 9.0). At pH 5.0, LSP had large particle size (1576.98 nm), high emulsion stability index (91.43 min), foaming stability (75.69%) and water holding capacity (2.21 g g-1), but low solubility (35.98%), free sulfhydryl content (1.95 µmol g-1) and surface hydrophobicity (780). DSC analysis showed the denaturation temperatures (82.23 °C) of LSP at pH 5.0 was higher than those (80.10, 80.52 and 71.82 °C) at pH 3.0, 7.0 and 9.0. The analysis of rheological properties showed that LSP gel had high stability and great strength in an alkaline environment. CONCLUSION: The findings of the present study are anticipated to serve as a valuable reference for the implementation of LSP in the food industry. © 2024 Society of Chemical Industry.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Lotus , Tamaño de la Partícula , Proteínas de Plantas , Semillas , Solubilidad , Semillas/química , Concentración de Iones de Hidrógeno , Lotus/química , Proteínas de Plantas/química , Reología , Emulsiones/química , Espectroscopía Infrarroja por Transformada de Fourier , Estructura Secundaria de Proteína
19.
Chin J Traumatol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39142966

RESUMEN

PURPOSE: To compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. METHODS: Thirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. RESULTS: Liver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p<0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p<0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p<0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p<0.001) and fibrinogen concentration (g/L) (1.188 ± 0.29 vs. 1.890 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.379 ± 0.32 vs. 0.051 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.675 ± 0.21 vs. 1.937 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. CONCLUSIONS: Modified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.

20.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 611-618, 2024 Jun 15.
Artículo en Zh | MEDLINE | ID: mdl-38926378

RESUMEN

OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.


Asunto(s)
Displasia Broncopulmonar , Recien Nacido Prematuro , Gemelos , Humanos , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/epidemiología , Factores de Riesgo , Recién Nacido , Femenino , Estudios Retrospectivos , Masculino , Edad Gestacional , Peso al Nacer , Modelos Logísticos
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