RESUMEN

BACKGROUND: Aorto-ostial (AO) coronary interventions may be associated with multiple problems, including the potential embolization of atherothrombotic debris into the aorta and systemic circulation. Such embolization could theoretically lead to stroke or silent brain injury (SBI). In this study, we aimed to investigate whether there is an increased risk of SBI in patients undergoing AO stent implantation. METHODS: Fifty-five consecutive patients undergoing AO stenting and 55 consecutive patients undergoing non-AO stenting were included. Venous blood samples were obtained before and 12 h after the procedure to measure neuron-specific enolase (NSE), which is a sensitive marker of brain injury. Newly developed NSE elevation after the procedure in an asymptomatic patient was defined as SBI. RESULTS: SBI was detected in 24 (43.6%) patients in the AO stenting group and 17 (30.9%) patients in the non-AO stenting group (p = .167). Although the SBI rates were statistically comparable between the groups, the presence of significant (≥50%) AO stenosis was found to be an independent predictor of SBI in multivariate logistic regression analysis [odds ratio (OR) 2.856; 95% confidence interval (CI) 1.057-7.716; p = .038]. A longer procedure time was another independent predictor for the development of SBI (OR 1.037; 95% CI 1.005-1.069; p = .023). CONCLUSION: This study suggests that AO stenting may be associated with an increased risk of SBI if the lesion in the ostium is significant.

Asunto(s)

Intervención Coronaria Percutánea , Fosfopiruvato Hidratasa , Stents , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Stents/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Fosfopiruvato Hidratasa/sangre , Lesiones Encefálicas/etiología , Factores de Riesgo , Biomarcadores/sangre

RESUMEN

PURPOSE OF REVIEW: There is growing evidence that enolase is involved in allergy. This manuscript reviews the impact of enolase in allergic disease and describes several sources of this allergen including molds, plants, animals, and pollens, among others. IgE epitopes are carefully analyzed as they may account for cross-reactivity. RECENT FINDINGS: Enolase has been previously associated to food allergy and contact dermatitis. However, other groups and we have identified recently novel enolases derived from diverse pollens in patients suffering asthma and allergic rhinitis. Exposure to outdoor enolases may cause respiratory disease. Enolase has been identified across various species and its amino acid sequence is highly conserved among different sources of this allergen. The demonstration that enolase is involved in many allergic diseases including respiratory allergies, is of clinic relevance. Thus, the development of novel molecular-based diagnostic and therapeutic strategies may pave the way for improved diagnosis and therapeutics.

Asunto(s)

Alérgenos , Hipersensibilidad , Fosfopiruvato Hidratasa , Humanos , Fosfopiruvato Hidratasa/inmunología , Animales , Alérgenos/inmunología , Hipersensibilidad/inmunología , Reacciones Cruzadas/inmunología , Inmunoglobulina E/inmunología , Polen/inmunología

RESUMEN

BACKGROUND: Basic helix-loop-helix ARNT like 2 (ARNTL2) is a transcription factor that controls the circadian rhythm. Amounts of studies have demonstrated the carcinogenic function of ARNTL2 in human malignant tumors albeit the underlying mechanisms remain poorly understood. We aimed to study the significance of ARNTL2 in bladder cancer (BLCA). METHODS: Immunohistochemical staining, immunoblotting and the database from TCGA were used to analyze the clinical relevance of ARNTL2, enolase 1 (ENO1) and solute carrier family 31 member 1 (SLC31A1) in BLCA. The function of ARNTL2 was explored by cell proliferation assay, apoptosis, colony formation and xenografted tumorigenesis. The molecular mechanisms of ARNTL2-driving BLCA development were investigated by RT-qPCR, immunoblotting and luciferase assays. Glycolysis was checked by measuring glucose consumption and lactate production. ENO1 activity was assessed by using indicated assay kit. RESULTS: Overexpression of ARNTL2 facilitates the proliferation and tumorigenesis of BLCA cells through suppression of apoptosis and enhancement of glycolysis. Up-regulation of SLC31A1, ENO1, and enhancement of SLC31A1-mediated ENO1 activity were critical for ARNTL2-triggered glycolysis and malignant growth in BLCA cells. ARNTL2 was positively correlated with SLC31A1 and ENO1 in BLCA patients. High expression of ARNTL2, SLC31A1 or ENO1 predicted the poor prognosis of BLCA patients. Depletion of SLC31A1 and inhibition of glycolysis completely blunted the growth ability of BLCA cells. CONCLUSION: In summary, ARNTL2 facilitates the progression of BLCA via activating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner. Inhibiting SLC31A1 and glycolysis may be an aspirational approach for the treatment of BLCA patients with overexpression of ARNTL2.

Asunto(s)

Factores de Transcripción ARNTL , Proliferación Celular , Proteínas de Unión al ADN , Glucólisis , Fosfopiruvato Hidratasa , Proteínas Supresoras de Tumor , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Humanos , Fosfopiruvato Hidratasa/metabolismo , Fosfopiruvato Hidratasa/genética , Animales , Ratones , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Línea Celular Tumoral , Progresión de la Enfermedad , Ratones Desnudos , Apoptosis , Femenino , Regulación Neoplásica de la Expresión Génica , Masculino , Ratones Endogámicos BALB C , Carcinogénesis/metabolismo , Carcinogénesis/genética , Biomarcadores de Tumor

RESUMEN

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used systemically. Here, we describe findings that demonstrate these agents are potent inhibitors of N. fowleri ENO (NfENO) and are lethal to amoebae. In particular, (1-hydroxy-2-oxopiperidin-3-yl) phosphonic acid (HEX) was a potent enzyme inhibitor (IC50 = 0.14 ± 0.04 µM) that was toxic to trophozoites (EC50 = 0.21 ± 0.02 µM) while the reported CC50 was >300 µM. Molecular docking simulation revealed that HEX binds strongly to the active site of NfENO with a binding affinity of -8.6 kcal/mol. Metabolomic studies of parasites treated with HEX revealed a 4.5 to 78-fold accumulation of glycolytic intermediates upstream of NfENO. Last, nasal instillation of HEX increased longevity of amoebae-infected rodents. Two days after infection, animals were treated for 10 days with 3 mg/kg HEX, followed by one week of observation. At the end of the one-week observation, eight of 12 HEX-treated animals remained alive (resulting in an indeterminable median survival time) while one of 12 vehicle-treated rodents remained, yielding a median survival time of 10.9 days. However, intranasal HEX delivery was not curative as brains of six of the eight survivors were positive for amoebae. These findings suggest that HEX requires further evaluation to develop as a lead for treatment of PAM.

Asunto(s)

Infecciones Protozoarias del Sistema Nervioso Central , Naegleria fowleri , Fosfopiruvato Hidratasa , Animales , Naegleria fowleri/efectos de los fármacos , Infecciones Protozoarias del Sistema Nervioso Central/tratamiento farmacológico , Infecciones Protozoarias del Sistema Nervioso Central/parasitología , Fosfopiruvato Hidratasa/metabolismo , Fosfopiruvato Hidratasa/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Ratones , Ratas , Humanos , Simulación del Acoplamiento Molecular

RESUMEN

BACKGROUND: The incidence of post-stroke depression (PSD) may be higher in patients with cancer-associated ischemic stroke (CAIS). The pathogenesis of PSD is mainly related to the emotional injury of stroke and the inability of neurons to effectively repair. This study aims to explore the clinical significance of serum neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) expression levels in CAIS patients. METHODS: Clinical data of 106 patients with CAIS admitted to Jinhua Guangfu Oncology Hospital from January 2012 to December 2022 were retrospectively analyzed. Serum levels of NSE, BDNF and CNTF were measured in all patients after admission. Depression screening was performed by Hamilton Depression Scale-17 (HAMD-17) three months after intravenous thrombolysis. Patients with HAMD-17 score >7 were included in the PSD group (n = 44), and patients with HAMD-17 score ≤7 were included in the non-PSD group (n = 62). The general data and serum levels of NSE, BDNF and CNTF were compared between the two groups. According to HAMD-17 scores, patients in PSD group were further divided into mild depression group (8-16 points), moderate depression group (17-23 points) and severe depression group (≥24 points), and the serum levels of NSE, BDNF and CNTF were compared among the three groups. Pearson's correlation test was used to analyze the correlation between HAMD-17 scores and serum NSE, BDNF and CNTF levels in PSD patients. Logistic regression model was used to determine the influencing factors of PSD in CAIS patients. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive efficacy of serum NSE, BDNF, CNTF and their combination on PSD. RESULTS: Among 106 CAIS patients, the incidence of PSD was 41.51% (44 cases), including 19 patients with mild PSD (43.18%), 14 patients with moderate PSD (31.82%), and 11 patients with severe PSD (25.00%). There were statistically significant differences in negative life events and complications after thrombolytic therapy between PSD and non-PSD patients (p < 0.05). The serum NSE level in PSD group was significantly higher than that in non-PSD group, and the serum BDNF and CNTF levels were notably lower than those in non-PSD group (all p < 0.001). The serum levels of NSE, BDNF and CNTF in patients with different severity of PSD were statistically significant (all p < 0.001). HAMD-17 scores in PSD patients were positively correlated with serum NSE levels (r = 0.676, p < 0.001) and negatively correlated with serum BDNF and CNTF levels (r = -0.661, p < 0.001; r = -0.401, p = 0.007, respectively). By binary logistic regression analysis, the levels of serum NSE, BDNF and CNTF were independent influencing factors for PSD in CAIS patients, among which NSE was a risk factor (odds ratio (OR) >1, p < 0.05), BDNF and CNTF were protective factors (OR <1, p < 0.05). CONCLUSION: This study reveals for the first time that the levels of serum NSE, BDNF and CNTF are closely related to the occurrence and development of PSD in CAIS patients. In clinical CAIS patients with abnormal changes in the above indicators, in addition to anti-tumor treatment and improvement of neurological deficit symptoms, attention should also be paid to the symptoms of psychological disorders.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , Factor Neurotrófico Ciliar , Depresión , Accidente Cerebrovascular Isquémico , Fosfopiruvato Hidratasa , Humanos , Factor Neurotrófico Derivado del Encéfalo/sangre , Masculino , Femenino , Fosfopiruvato Hidratasa/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/complicaciones , Depresión/sangre , Depresión/etiología , Factor Neurotrófico Ciliar/sangre , Anciano , Neoplasias/complicaciones , Neoplasias/sangre , Relevancia Clínica

RESUMEN

Purpose: Central retinal artery occlusion (CRAO) is an ocular emergency that results from acute blockage of the blood supply to the retina and leads to a sudden vision loss. Other forms of ischemic retinopathies include diabetic retinopathy (DR), which involves chronic retinal ischemia and remains the leading cause of blindness in working-age adults. This study is the first to conduct a proteomic analysis of aqueous humor (AH) from patients with CRAO with a comparative analysis using vitreous humor (VH) samples from patients with DR. Methods: AH samples were collected from 10 patients with CRAO undergoing paracentesis and 10 controls undergoing cataract surgery. VH samples were collected from 10 patients with DR and 10 non-diabetic controls undergoing pars plana vitrectomy (PPV). Samples were analyzed using mass spectrometry. Results: Compared with controls, AH levels of 36 differentially expressed proteins (DEPs) were identified in patients with CRAO. Qiagen Ingenuity Pathway Analysis (IPA) revealed 11 proteins linked to ophthalmic diseases. Notably, enolase 2, a glycolysis enzyme isoform primarily expressed in neurons, was upregulated, suggesting neuronal injury and enzyme release. Additionally, clusterin, a protective glycoprotein, was downregulated. ELISA was conducted to confirm proteomics data. VH samples from patients with DR exhibited changes in a distinct set of proteins, including ones previously reported in the literature. Conclusions: The study provides novel insights into CRAO pathophysiology with multiple hits identified. Proteomic results differed between DR and CRAO studies, likely due to the different pathophysiology and disease duration. Translational Relevance: This is the first proteomic analysis of CRAO AH, with the potential to identify future therapeutic targets.

Asunto(s)

Humor Acuoso , Proteómica , Oclusión de la Arteria Retiniana , Humanos , Humor Acuoso/metabolismo , Humor Acuoso/química , Proteómica/métodos , Oclusión de la Arteria Retiniana/metabolismo , Masculino , Femenino , Anciano , Persona de Mediana Edad , Proteínas del Ojo/metabolismo , Cuerpo Vítreo/metabolismo , Vitrectomía , Fosfopiruvato Hidratasa/metabolismo , Paracentesis , Espectrometría de Masas

RESUMEN

AIM: To observe changes in the serum levels of visinin-like protein-1 (VILIP-1), caveolin-1 (Cav-1) and neuron-specific enolase (NSE) after glioma resection. MATERIAL AND METHODS: Consecutive 14 glioma patients with different histologic grade and 14 age and gender-matched healthy subjects were included in this pilot study. From the patients serum samples were taken in preoperative and on day 2 and 10 of postoperative periods. Healthy subjects provided serum sample once. The serum changes of three proteins were evaluated by ELISA. The results were compared between preoperative and postoperative periods and between patients and controls. RESULTS: Preoperative serum levels of VILIP-1 (p=0.008) and Cav-1 (p=0.012) were significantly higher in the patients. Mean serum levels of VILIP-1 (p=0.002) and Cav-1 (p=0.013) again were significantly higher than those of the controls. NSE did not show significant changes compared to controls in none of the periods. There was a steady decline regarding all three molecules from preoperative to postoperative day 10. However, statistical comparisons did not reveal any significant difference with respect the decline in any molecule. Significant positive correlation was detected between preoperative serum levels of VILIP-1 and Cav-1 (p=0.00001) in the patients and the controls (p=0.0000). CONCLUSION: This pilot study suggested that Cav-1 and particularly VILIP-1 may be used as a valuable serum biomarker for follow-up and for early detection of recurrence in high-grade gliomas. Future studies including larger cohort of patients with homogeneous group of glioma is required.

Asunto(s)

Caveolina 1 , Glioma , Neurocalcina , Fosfopiruvato Hidratasa , Neoplasias Supratentoriales , Humanos , Caveolina 1/sangre , Fosfopiruvato Hidratasa/sangre , Proyectos Piloto , Masculino , Glioma/cirugía , Glioma/sangre , Femenino , Persona de Mediana Edad , Adulto , Neoplasias Supratentoriales/cirugía , Neoplasias Supratentoriales/sangre , Neurocalcina/sangre , Biomarcadores de Tumor/sangre , Anciano , Periodo Posoperatorio

RESUMEN

In this paper, Bi2S3/AgBiS2 composite nanomaterials and PDA@Ag@N-CQDs were synthesized, and used as substrates and second antibody label respectively to construct a sandwich photoelectrochemical (PEC) sensor. The upconversion luminescence effect of N-CQDs can convert long wavelength light into short wavelength light that can be utilized by the substrate material, which can provide additional excitation light energy for the substrate material and further enhance the photoelectric response. Besides, Ag has SPR effect and can also promote electron transfer. The proposed sandwich immunosensor achieves detection of NSE in the concentration range of 0.001 ng mL-1 to 100 ng mL-1, with a detection limit of 0.28 pg mL-1 (S/N = 3). What's more, the proposed sensor also exhibits good stability, selectivity, as well as reproducibility, indicating its promising application prospects.

Asunto(s)

Bismuto , Técnicas Electroquímicas , Fosfopiruvato Hidratasa , Plata , Plata/química , Fosfopiruvato Hidratasa/análisis , Bismuto/química , Humanos , Técnicas Biosensibles/métodos , Límite de Detección , Procesos Fotoquímicos , Luminiscencia , Sulfuros/química

RESUMEN

In this work, a photoelectrochemical (PEC) immunosensor was constructed for the ultrasensitive detection of lung cancer marker neuron-specific enolase (NSE) based on a microflower-like heterojunction of cadmium indium sulfide and magnesium indium sulfide (CdIn2S4/MgIn2S4, CMIS) as photoactive material. Specifically, the well-matched energy level structure and narrow energy level gradients between CdIn2S4 and MgIn2S4 could accelerate the separation of electron-hole (e--h+) pairs in the CMIS heterojunction to enhance the photocurrent of CMIS, which was increased 5.5 and 80 times compared with that of single CdIn2S4 and MgIn2S4, respectively. Meanwhile, using CMIS as photoactive material, increasing the biocompatibility by dropping Pt NPs on the surface of CMIS to immobilize the antibody through Pt-N bond. Fe3O4-Ab2, acting as the quencher, competitively consumes electron donors and absorbs light, leading to photocurrent quenching. With the increasing of quencher, the photocurrent decreased. Hence, the developed "signal-off" PEC immunosensor realized the trace detection of NSE within the range from 1.0 fg/mL to 10 ng/mL with a low detection limit of 0.34 fg/mL. This strategy provided a new perspective for establishing ternary metal sulfide heterojunction to construct PEC immunosensor for sensitive detection of disease biomarkers.

Asunto(s)

Biomarcadores de Tumor , Indio , Neoplasias Pulmonares , Fosfopiruvato Hidratasa , Sulfuros , Humanos , Fosfopiruvato Hidratasa/análisis , Indio/química , Biomarcadores de Tumor/análisis , Sulfuros/química , Límite de Detección , Técnicas Electroquímicas , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Compuestos de Cadmio/química , Anticuerpos Inmovilizados/inmunología , Anticuerpos Inmovilizados/química

RESUMEN

AIM: To investigate the performance of the 2021 ERC/ESICM-recommended algorithm for predicting poor outcome after cardiac arrest (CA) and potential tools for predicting neurological recovery in patients with indeterminate outcome. METHODS: Prospective, multicenter study on out-of-hospital CA survivors from 28 ICUs of the AfterROSC network. In patients comatose with a Glasgow Coma Scale motor score ≤3 at ≥72 h after resuscitation, we measured: (1) the accuracy of neurological examination, biomarkers (neuron-specific enolase, NSE), electrophysiology (EEG and SSEP) and neuroimaging (brain CT and MRI) for predicting poor outcome (modified Rankin scale score ≥4 at 90 days), and (2) the ability of low or decreasing NSE levels and benign EEG to predict good outcome in patients whose prognosis remained indeterminate. RESULTS: Among 337 included patients, the ERC-ESICM algorithm predicted poor neurological outcome in 175 patients, and the positive predictive value for an unfavourable outcome was 100% [98-100]%. The specificity of individual predictors ranged from 90% for EEG to 100% for clinical examination and SSEP. Among the remaining 162 patients with indeterminate outcome, a combination of 2 favourable signs predicted good outcome with 99[96-100]% specificity and 23[11-38]% sensitivity. CONCLUSION: All comatose resuscitated patients who fulfilled the ERC-ESICM criteria for poor outcome after CA had poor outcome at three months, even if a self-fulfilling prophecy cannot be completely excluded. In patients with indeterminate outcome (half of the population), favourable signs predicted neurological recovery, reducing prognostic uncertainty.

Asunto(s)

Algoritmos , Electroencefalografía , Paro Cardíaco Extrahospitalario , Humanos , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/mortalidad , Anciano , Pronóstico , Electroencefalografía/métodos , Examen Neurológico/métodos , Coma/etiología , Coma/diagnóstico , Reanimación Cardiopulmonar/métodos , Fosfopiruvato Hidratasa/sangre , Biomarcadores/sangre , Escala de Coma de Glasgow , Valor Predictivo de las Pruebas , Neuroimagen/métodos , Potenciales Evocados Somatosensoriales

RESUMEN

PURPOSE: Infantile epileptic spasms syndrome (IESS) with epileptic spasms as the main seizure type, is treated with adrenocorticotropic hormone (ACTH). This study, for the first time, examines the effects of epileptic spasms and ACTH on blood-brain barrier (BBB) permeability in patients with IESS of unknown etiology. METHODS: We prospectively evaluated the changes in BBB permeability in patients with IESS of unknown etiology at the Saitama Children's Medical Center between February 2012 and February 2024. We compared the levels of serum-albumin, cerebrospinal fluid (CSF)-albumin, Q-albumin, and CSF-neuron-specific enolase (NSE) before and after ACTH therapy. We also assessed the correlation between the frequency of epileptic spasms and these markers. RESULTS: Overall, 16 patients with IESS (8 males) were included in the study. The median age at IESS onset was 5 (range, 2-9) months. The median duration between the epileptic spasms onset and the serum and CSF sample examination before ACTH therapy was 26 (range, 1-154) days. After ACTH therapy, CSF-albumin and Q-albumin levels significantly decreased (CSF-albumin: 13.5 (9.0-32.0) mg/dL vs 11.0 (7.0-19.0) mg/dL, p = 0.001. Q-albumin: 3.7× 10-3 (2.2 × 10-3-7.3 × 10-3) vs 2.8× 10-3 (1.9 × 10-3-4.5 × 10-3), p = 0.003). No correlation was observed between the epileptic spasms frequency and levels of serum-albumin, CSF-albumin, Q-albumin, and CSF-NSE (Spearman's coefficient: r = 0.291, r = 0.141, r = 0.094, and r = -0.471, respectively). CONCLUSION: ACTH therapy is one of the factors that play a role in restoring BBB permeability in patients with IESS of unknown etiology. Our findings may be useful in elucidating the mechanism of ACTH action and IESS pathophysiology.

Asunto(s)

Hormona Adrenocorticotrópica , Espasmos Infantiles , Humanos , Hormona Adrenocorticotrópica/sangre , Masculino , Femenino , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/sangre , Lactante , Estudios Prospectivos , Barrera Hematoencefálica/efectos de los fármacos , Albúminas/líquido cefalorraquídeo , Fosfopiruvato Hidratasa/sangre , Fosfopiruvato Hidratasa/líquido cefalorraquídeo

RESUMEN

Enolase is a 47 kDa enzyme that functions within the glycolysis and gluconeogenesis pathways involved in the reversible conversion of D-2-phosphoglycerate (2PGA) to phosphoenolpyruvate (PEP). However, in the context of host-pathogen interactions, enolase from different species of parasites, fungi and bacteria have been shown to contribute to adhesion processes by binding to proteins of the host extracellular matrix (ECM), such as fibronectin (FN) or laminin (LM). In addition, enolase is a plasminogen (PLG)-binding protein and induces its activation to plasmin, the main protease of the host fibrinolytic system. These secondary 'moonlighting' functions of enolase are suggested to facilitate pathogen migration through host tissues. This study aims to uncover the moonlighting role of enolase from the parasite Fasciola hepatica, shedding light on its relevance to host-parasite interactions in fasciolosis, a global zoonotic disease of increasing concern. A purified recombinant form of F. hepatica enolase (rFhENO), functioning as an active homodimeric glycolytic enzyme of ~94 kDa, was successfully obtained, fulfilling its canonical role. Immunoblotting studies on adult worm extracts showed that the enzyme is present in the tegument and the excretory/secretory products of the parasite, which supports its key role at the host-parasite interface. Confocal immunolocalisation studies of the protein in newly excysted juveniles and adult worms also localised its expression within the parasite tegument. Finally, we showed by ELISA that rFhENO can act as a parasitic adhesin by binding host LM, but not FN. rFhENO also binds PLG and enhances its conversion to plasmin in the presence of the tissue-type and urokinase-type PLG activators (t-PA and u-PA). This moonlighting adhesion-like function of the glycolytic protein enolase could contribute to the mechanisms by which F. hepatica efficiently invades and migrates within its host and encourages further research efforts that are designed to impede this function by vaccination or drug design.

Asunto(s)

Matriz Extracelular , Fasciola hepatica , Interacciones Huésped-Parásitos , Fosfopiruvato Hidratasa , Fosfopiruvato Hidratasa/metabolismo , Fosfopiruvato Hidratasa/genética , Fasciola hepatica/enzimología , Fasciola hepatica/metabolismo , Animales , Matriz Extracelular/metabolismo , Fibrinólisis , Plasminógeno/metabolismo , Glucólisis , Fascioliasis/parasitología , Fascioliasis/metabolismo , Laminina/metabolismo

RESUMEN

Background and Objectives: Silent cerebral ischemia (SCI) is defined as a condition that can be detected by biochemical markers or cranial imaging methods but does not produce clinical symptom. This study aims both to compare the frequency of SCI in PCIs performed with right transradial access and left transradial access and to evaluate the influencing factors. Materials and Methods: A prospective, single-center study included 197 patients undergoing PCI via transradial access between November 2020 and July 2022. The patients were categorized into right radial and left radial groups. Neuron-specific enolase (NSE) values were measured and recorded before and 18 h after the procedure. A post-procedure NSE level higher than 20 ng/dL was defined as SCI. Results: SCI occurred in 60 of the 197 patients. NSE elevation was observed in 37.4% (n = 37) of the right radial group and in 23.5% (n = 23) of the left radial group (p = 0.032). Patients with SCI had higher rates of smoking (p = 0.043), presence of subclavian tortuosity (p = 0.027), and HbA1c (p = 0.031). In the multivariate logistic regression analysis, the level of EF (ejection fraction) (OR: 0.958 95% CI 0.920-0.998, p = 0.039), right radial preference (OR: 2.104 95% CI 1.102-3.995 p = 0.023), and smoking (OR: 2.088 95% CI 1.105-3.944, p = 0.023) were observed as independent variables of NSE elevation. Conclusions: Our findings suggest that PCI via right radial access poses a greater risk of SCI compared to left radial access. Anatomical considerations and technical challenges associated with right radial procedures and factors such as smoking and low ejection fraction contribute to this elevated risk.

Asunto(s)

Isquemia Encefálica , Intervención Coronaria Percutánea , Arteria Radial , Humanos , Femenino , Masculino , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Persona de Mediana Edad , Arteria Radial/cirugía , Anciano , Estudios Prospectivos , Isquemia Encefálica/etiología , Fosfopiruvato Hidratasa/sangre , Fosfopiruvato Hidratasa/análisis , Factores de Riesgo , Modelos Logísticos

RESUMEN

We read with great interest the review article on pathophysiology and treatment based on different out-of-hospital cardiac arrest (OHCA) patients. We wish to present our comments on the threshold values for neuron-specific enolase (NSE) based on the initial rhythm and the misquoting of a few references in that article.

Asunto(s)

Paro Cardíaco Extrahospitalario , Fosfopiruvato Hidratasa , Humanos , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/fisiopatología , Fosfopiruvato Hidratasa/sangre , Resultado del Tratamiento , Reanimación Cardiopulmonar/métodos

RESUMEN

Background and Objectives: Most patients who are successfully resuscitated from cardiac arrest remain comatose, and only half regain consciousness 72 h after the arrest. Neuroprognostication methods can be complex and even inconclusive. As mitochondrial components have been identified as markers of post-cardiac-arrest injury and associated with survival, we aimed to investigate cytochrome c and mtDNA in comatose patients after cardiac arrest to compare neurological outcomes and to evaluate the markers' neuroprognostic value. Materials and Methods: This prospective observational study included 86 comatose post-cardiac-arrest patients and 10 healthy controls. Cytochrome c and mtDNA were determined at admission. Neuron-specific enolase (NSE) was measured after 72 h. Additional neuroprognostication methods were performed when patients remained unconscious. Cerebral performance category (CPC) was determined. Results: Cytochrome c was elevated in patients compared to healthy controls (2.029 [0.85-4.97] ng/mL vs. 0 [0.0-0.16], p < 0.001) but not mtDNA (95,228 [52,566-194,060] vs. 41,466 [28,199-104,708] copies/µL, p = 0.074). Compared to patients with CPC 1-2, patients with CPC 3-5 had higher cytochrome c (1.735 [0.717-3.40] vs. 4.109 [1.149-8.457] ng/mL, p = 0.011), with no differences in mtDNA (87,855 [47,598-172,464] vs. 126,452 [69,447-260,334] copies/µL, p = 0.208). Patients with CPC 1-2 and CPC 3-5 differed in all neuroprognostication methods. In patients with good vs. poor neurological outcome, ROC AUC was 0.664 (p = 0.011) for cytochrome c, 0.582 (p = 0.208) for mtDNA, and 0.860 (p < 0.001) for NSE. The correlation between NSE and cytochrome c was moderate, with a coefficient of 0.576 (p < 0.001). Conclusions: Cytochrome c was higher in comatose patients after cardiac arrest compared to healthy controls and higher in post-cardiac-arrest patients with poor neurological outcomes. Although cytochrome c correlated with NSE, its neuroprognostic value was poor. We found no differences in mtDNA.

Asunto(s)

Biomarcadores , Coma , Citocromos c , Paro Cardíaco , Humanos , Coma/etiología , Coma/fisiopatología , Masculino , Femenino , Estudios Prospectivos , Paro Cardíaco/complicaciones , Persona de Mediana Edad , Biomarcadores/análisis , Biomarcadores/sangre , Anciano , Citocromos c/análisis , Citocromos c/sangre , ADN Mitocondrial/análisis , Fosfopiruvato Hidratasa/sangre , Fosfopiruvato Hidratasa/análisis , Mitocondrias , Adulto

RESUMEN

In this study, we aim to investigate the role of enolase 1 (ENO1) in osteoarthritis (OA) pathogenic process and to uncover the underlying mechanism. To this end, we used IL-1ß to induce an in vitro OA­like chondrocyte model in human immortalized chondrocyte C-28/I2 cells. We manipulated the expression of ENO1 and cytokine receptor-like factor 1 (CRLF1) in IL-1ß-induced C-28/I2 cells using siRNA and/or overexpression and tested their effects on IL-1ß-induced pathologies including cell viability, apoptosis and inflammatory cytokine levels (IL-6 and TNF-α), and the expression of extracellular matrix-related enzymes and major mediators in the NF-κB signaling pathway (p-p65, p65, p-IκBα and IκBα). We used co-immunoprecipitation and immunofluorescence imaging to study a possible binding between ENO1 and CRLF1. Our data showed that IL-1ß induction elevated ENO1 and CRLF1 expression in C-28/I2 cells. Silencing ENO1 or CRLF1 inhibited the IL-1ß-induced cell viability damage, apoptosis, inflammation, and extracellular matrix degradation. The inhibitory effect of silencing ENO1 was reversed by CRLF1 overexpression, suggesting a functional connection between ENO1 and CRLF1, which could be attributed to a binding between these two partners. Our study could help validate the role of ENO1 in OA pathogenies and identify novel therapeutic targets for OA treatment.

Asunto(s)

Apoptosis , Condrocitos , Proteínas de Unión al ADN , Matriz Extracelular , Inflamación , Interleucina-1beta , Fosfopiruvato Hidratasa , Proteínas Supresoras de Tumor , Condrocitos/metabolismo , Condrocitos/patología , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacología , Inflamación/metabolismo , Inflamación/patología , Matriz Extracelular/metabolismo , Fosfopiruvato Hidratasa/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Receptores de Citocinas/metabolismo , Receptores de Citocinas/genética , Unión Proteica , Osteoartritis/metabolismo , Osteoartritis/patología , Transducción de Señal , FN-kappa B/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Biomarcadores de Tumor

RESUMEN

Introduction: Pancreatic Ductal Adenocarcinoma (PDA) is one of the most aggressive malignancies with a 5-year survival rate of 13%. Less than 20% of patients have a resectable tumor at diagnosis due to the lack of distinctive symptoms and reliable biomarkers. PDA is resistant to chemotherapy (CT) and understanding how to gain an anti-tumor effector response following stimulation is, therefore, critical for setting up an effective immunotherapy. Methods: Proliferation, and cytokine release and TCRB repertoire of from PDA patient peripheral T lymphocytes, before and after CT, were analyzed in vitro in response to four tumor-associated antigens (TAA), namely ENO1, FUBP1, GAPDH and K2C8. Transcriptional state of PDA patient PBMC was investigated using RNA-Seq before and after CT. Results: CT increased the number of TAA recognized by T lymphocytes, which positively correlated with patient survival, and high IFN-γ production TAA-induced responses were significantly increased after CT. We found that some ENO1-stimulated T cell clonotypes from CT-treated patients were expanded or de-novo induced, and that some clonotypes were reduced or even disappeared after CT. Patients that showed a higher number of effector responses to TAA (high IFN-γ/IL-10 ratio) after CT expressed increased fatty acid-related transcriptional signature. Conversely, patients that showed a higher number of regulatory responses to TAA (low IFN-γ/IL-10 ratio) after CT significantly expressed an increased IRAK1/IL1R axis-related transcriptional signature. Conclusion: These data suggest that the expression of fatty acid or IRAK1/IL1Rrelated genes predicts T lymphocyte effector or regulatory responses to TAA in patients that undergo CT. These findings are a springboard to set up precision immunotherapies in PDA based on the TAA vaccination in combination with CT.

Asunto(s)

Antígenos de Neoplasias , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Masculino , Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/genética , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Femenino , Transcriptoma , Anciano , Persona de Mediana Edad , Linfocitos T/inmunología , Linfocitos T/metabolismo , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología

RESUMEN

Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.

Asunto(s)

Antifúngicos , Candida albicans , Chalconas , Glucólisis , Fosfopiruvato Hidratasa , Candida albicans/efectos de los fármacos , Fosfopiruvato Hidratasa/metabolismo , Fosfopiruvato Hidratasa/antagonistas & inhibidores , Fosfopiruvato Hidratasa/genética , Antifúngicos/farmacología , Antifúngicos/química , Chalconas/farmacología , Chalconas/química , Glucólisis/efectos de los fármacos , Ratones , Animales , Humanos , Candidiasis/tratamiento farmacológico , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/antagonistas & inhibidores , Pruebas de Sensibilidad Microbiana , Proteínas de Unión al ADN , Biomarcadores de Tumor , Proteínas Supresoras de Tumor

RESUMEN

CD4+ T cells recognising citrullinated self-epitopes presented by HLA-DRB1 bearing the shared susceptibility epitope (SE) are implicated in rheumatoid arthritis (RA). However, the underlying T cell receptor (TCR) determinants of epitope specificity towards distinct citrullinated peptide antigens, including vimentin-64cit59-71 and α-enolase-15cit10-22 remain unclear. Using HLA-DR4-tetramers, we examine the T cell repertoire in HLA-DR4 transgenic mice and observe biased TRAV6 TCR gene usage across these two citrullinated epitopes which matches with TCR bias previously observed towards the fibrinogen ß-74cit69-81 epitope. Moreover, shared TRAV26-1 gene usage is evident in four α-enolase-15cit10-22 reactive T cells in three human samples. Crystal structures of mouse TRAV6+ and human TRAV26-1+ TCR-HLA-DR4 complexes presenting vimentin-64cit59-71 and α-enolase-15cit10-22, respectively, show three-way interactions between the TCR, SE, citrulline, and the basis for the biased selection of TRAV genes. Position 2 of the citrullinated epitope is a key determinant underpinning TCR specificity. Accordingly, we provide a molecular basis of TCR specificity towards citrullinated epitopes.

Asunto(s)

Artritis Reumatoide , Linfocitos T CD4-Positivos , Antígeno HLA-DR4 , Ratones Transgénicos , Vimentina , Humanos , Antígeno HLA-DR4/inmunología , Antígeno HLA-DR4/genética , Artritis Reumatoide/inmunología , Artritis Reumatoide/genética , Ratones , Animales , Vimentina/inmunología , Vimentina/metabolismo , Vimentina/genética , Linfocitos T CD4-Positivos/inmunología , Citrulinación , Fosfopiruvato Hidratasa/inmunología , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , Epítopos de Linfocito T/inmunología , Citrulina/metabolismo , Citrulina/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Epítopos/inmunología , Cristalografía por Rayos X , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo

RESUMEN

OBJECTIVE: To explore the prognostic value of interleukin-6 (IL-6) combined with serum neuron specific enolase (NSE) in arterial atherosclerotic ischemic stroke. METHODS: 116 patients with arterial atherosclerotic ischemic stroke admitted to the emergency ward of our Hospital were retrospectively analyzed. According to the score of modified Rankin scale (mRS) at 90 days after discharge, the patients were divided into the poor prognosis group (mRS > 2, n = 32) and the good prognosis group (mRS ≤ 2, n = 84). Activities of Daily Living (ADL) was used to evaluate the level of independence in activities of daily living after treatment. RESULTS: The NIHSS score (14.91 ± 5.20 vs. 9.43 ± 4.30, P < 0.001), IL-6 (11.30 ± 3.11 vs. 6.75±1.28, P < 0.001) and NSE levels (12.47 ± 4.69 vs. 6.42 ± 1.32, P<0.001) in poor prognosis group were higher than those in the good prognosis group. At 90 days post-discharge, 100 % of the good prognosis group had ADL scores over 60, while in the poor prognosis group, 46.88 % scored 40-60, 40.63 % scored 20-40, 9.38 % scored under 20, and 3.13 % died. The AUC of NSE was 0.906 (95 % CI: 0.847-0.965, P < 0.001), the best cut-off value was 7.445 ng/mL, and the sensitivity and specificity were 75.0 % and 82.1 %, respectively. The AUC for IL-6 combined with NSE increased to 0.965 (95 %CI: 0.934-0.997, P < 0.001), and the sensitivity and specificity increased to 80.2 % and 92.9 %, respectively. CONCLUSION: IL-6 ≥ 6.805 pg/mL and NSE ≥ 7.445 ng/mL were independently associated with poor prognosis in patients with AIS, and the combined testing of the two indicators had a higher predictive value. These results suggested that the combined assay of IL-6 and NSE could be a novel marker for predicting poor prognosis in AIS.

Asunto(s)

Interleucina-6 , Accidente Cerebrovascular Isquémico , Fosfopiruvato Hidratasa , Valor Predictivo de las Pruebas , Humanos , Fosfopiruvato Hidratasa/sangre , Interleucina-6/sangre , Masculino , Femenino , Anciano , Pronóstico , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , Biomarcadores/sangre , Actividades Cotidianas