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BACKGROUND: Calcification is common in advanced atheromatous plaque, but its clinical significance remains unclear. This study aimed to assess the prevalence of plaque calcification in the moderate-to-severe internal carotid artery stenosis and investigate its relationship with ipsilateral ischemia. METHODS: The retrospective study included 178 patients detected with proximal internal carotid artery (pICA) stenosis of ≥ 50% on multidetector computed tomography at Zhejiang Hospital from January 2019 to March 2023. Association between plaque calcification characteristics (calcification thickness, position, type, circumferential extent, calcium volume and calcium score) and ipsilateral cerebrovascular events was analyzed. RESULTS: The 178 patients (mean age 71.24 ± 10.02 years, 79.78% males) had 224 stenosed pICAs overall. Plaque calcification was noted in 200/224 (89.29%) arteries. Calcification rates were higher in older age-groups. Calcification volume (r = 0.219, p < 0.001) and calcification score (r = 0.230, p < 0.001) were correlated with age. Ipsilateral ischemic events were significantly more common in the noncalcification group than in the calcification group (χ2 = 4.160, p = 0.041). The most common calcification type was positive rim sign calcification (87/200, 43.50%), followed by bulky calcification (66/200, 33.00%); both were significantly associated with ischemic events (χ2 = 10.448, p = 0.001 and χ2 = 4.552, p = 0.033, respectively). Calcification position, thickness, and circumferential extent, and calcification volume and score, were not associated with ischemic events. In multivariate analysis, positive rim signs (OR = 2.795, 95%CI 1.182-6.608, p = 0.019) was an independent predictor of ischemic events. CONCLUSIONS: Plaque calcification in proximal internal carotid artery is common, and prevalence increases with age. Calcification characteristics could be predictive of ipsilateral ischemic events. The positive rim sign within plaque is a high-risk factor for a future ischemic event.
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Arteria Carótida Interna , Estenosis Carotídea , Humanos , Estenosis Carotídea/epidemiología , Estenosis Carotídea/diagnóstico por imagen , Estudios Retrospectivos , Masculino , Femenino , Anciano , Prevalencia , Persona de Mediana Edad , Anciano de 80 o más Años , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/patología , Calcificación Vascular/epidemiología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patología , Placa Aterosclerótica/epidemiología , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Calcinosis/epidemiología , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Tomografía Computarizada Multidetector/métodosRESUMEN
To elucidate the potential molecular mechanisms of ZBTB20-AS1 on ZBTB20 and GSK-3ß/Tau signaling pathway in the pathogenesis of Alzheimer's disease (AD), SH-SY5Y cells were obtained for in vitro experiments and AD models were constructed using ß-Amyloid 1-42. CCK8 assay was implemented for determining cell viability. Flow cytometry was used for cell apoptosis detection. Dual-luciferase reporter and RNA-RNA pull down assay was employed for elucidating molecular interactions. Immunohistochemistry, RT-qPCR and western blotting were performed for measuring gene expression. The results showed that expression of LncRNA ZBTB20-AS1 was significantly upregulated, while ZBTB20 was downregulated in SH-SY5Y-AD cells. ZBTB20 was the target gene of LncRNA ZBTB20-AS1. Overexpression of ZBTB20 or knockdown of LncRNA ZBTB20-AS1 inhibited SH-SY5Y-AD cells apoptosis and suppressed GSK3ß/Tau pathway, and knockdown of ZBTB20-AS1 increased cell viability and decreased apoptosis. In conclusion, overexpression of ZBTB20-AS1 inhibited ZBTB20 expression and promoted GSK-3ß expression and Tau phosphorylation, contributing to the development of AD.
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Enfermedad de Alzheimer , Glucógeno Sintasa Quinasa 3 beta , MicroARNs , Proteínas del Tejido Nervioso , ARN Largo no Codificante , Proteínas tau , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Apoptosis , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , MicroARNs/genética , Proteínas del Tejido Nervioso/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción , Proteínas tau/metabolismoRESUMEN
Hydrogenation of diesters to diols is a vital process for chemical industry. The inexpensive Cu+ /Cu0 -based catalysts are highly active for the hydrogenation of esters, however, how to efficiently tune the ratio of Cu+ /Cu0 and stabilize the Cu+ is a great challenge. In this work, it is demonstrated that doped Ti ions can tune the ratio of Cu+ /Cu0 and stabilize the Cu+ by the TiOCu bonds in Ti-doped SiO2 supported Cu nanoparticle (Cu/Ti-SiO2 ) catalysts for the high conversion of dimethyl adipate to 1,6-hexanediol. In the synthesis of the catalysts, the Ti4+ OCu2+ bonds promote the reduction of Cu2+ to Cu+ by forming Ti3+ OV Cu+ (OV : oxygen vacancy) bonds and the amount of Ti doping can tune the ratio of Cu+ /Cu0 . In the catalytic reaction, the O vacancy activates CO in the ester by forming new Ti3+ δ OR Cu1+ δ bonds (OR : reactant oxygen), and Cu0 activates hydrogen. After the products are desorbed, the Ti3+ δ OR Cu1+ δ bonds return to the initial state of Ti3+ OV Cu+ bonds. The reversible TiOCu bonds greatly improve the activity and stability of the Cu/Ti-SiO2 catalysts. When the content of Ti is controlled at 0.4 wt%, the conversion and selectivity can reach 100% and 98.8%, respectively, and remain stable for 260 h without performance degradation.
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BACKGROUND: Yuba is a soy protein-lipid film formed during heating of soymilk. This study described yuba as an edible film by analyzing its chemical composition, water vapor permeability (WVP), and mechanical properties. Three yuba films were prepared by using different concentrations and depths of soymilk: HS (86 g kg-1 and 2.3 cm), LS (70 g kg-1 and 2.3 cm), and LD (70 g kg-1 and 3.0 cm). RESULTS: As yuba was successively skimmed, the protein, lipid, and SH content decreased, but carbohydrate and SS content increased. Though both the initial concentration and the depth of soymilk affect the properties of the films, the depth of soymilk influences WVP and tensile strength (TS) more. The WVP of the HS and LS changed the least (13-17 g mm kPa-1 m-2 day1 ), while that of the LD changed the most (13-35 g mm kPa-1 m-2 day-1 ). There were no differences (P > 0.05) in the TS between the HS and LS. LD had the greatest decrease of TS and the lowest TS among the groups. The earlier the yuba films were collected, the greater the elongation of the films was: 129% (HS), 113% (LS), and 155% (LD). CONCLUSION: The initial concentration and the depth of soymilk changed the chemical composition and structure of the yuba films. The LS yuba produced more uniform edible films with good mechanical properties. © 2017 Society of Chemical Industry.
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Carbohidratos/química , Extractos Vegetales/química , Leche de Soja/química , Agua/química , Embalaje de Alimentos/instrumentación , Permeabilidad , Solubilidad , Proteínas de Soja/química , Resistencia a la TracciónRESUMEN
Antibody mimetics represent the fourth generation of antibody engineering, following polyclonal antibodies, monoclonal antibodies, and genetically engineered antibody fragments. Despite cumulative studies highlighting the advantages of antibody mimetics, including enhanced recognition properties, superior affinity, stability, penetrability, and cost-effectiveness, a comprehensive review of this evolving field is notably absent. In this study, spanning 1986-2023 and analyzing 24,318 publications, we undertake a retrospective and prospective analysis to elucidate the evolution roadmap of antibody mimetics, providing insights into the current landscape, global contributions, and future trajectories. Concurrently, our aim is to establish standardized terminology and delineate the research scope within the realm of antibody mimetics. These endeavors not only chart the trajectory and scope of antibody mimetics research but also underscore its potential to revolutionize medicine, technology, and science.
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Anticuerpos Monoclonales , Ingeniería Genética , Estudios Retrospectivos , BiomiméticaRESUMEN
To evaluate the right atrial function in patients with 3-branch coronary artery disease (TBCAD) without myocardial infarction by 2D speckle tracking echocardiography (2D-STE) combined with real-time 3-dimensional echocardiography (RT-3DE). Fifty-six patients admitted to our hospital without myocardial infarction with TBCAD were selected. We divided them into 2 groups according to the coronary angiography results: 28 patients in group B (the rate of stenosis is 50% ~< 75%); 28 patients in group C (the rate of stenosis isâ ≥75%); in addition, 30 healthy volunteers were screened as group A. All subjects underwent RT-3DE to obtain the right atrial volume (RAVmax, RAVmin, and RAVp), and then we calculated the right atrial passive and active ejection fraction (RAPEF, RAAEF), and maximum volume index (RAVImax). In addition, to measure the strain rates (RASRs, RASRe, RASRa) of the right atrium during systole, early diastole, and late diastole, 2D-STE was applied. Correlations between the 2D-STE parameters and the results of N-terminal pro-brain natriuretic peptide (NT-proBNP) and Gensini scores were analyzed by Pearson linear analysis. Compared with group A, RAPEF and RASRe were reduced, while RAAEF and RASRa were elevated in group B (Pâ <â .05). RAPEF, RASRs, RASRe, and RASRa were decreased compared with groups A and B, while RAVmax, RAVmin, RAVp, RAVImax, and RAAEF were increased in group C (Pâ <â .05). There was a significant correlation between 2D-STE parameters and the results of NT-proBNP and Gensini scores (Pâ <â .05). The storage, conduit, and pump functions of the right atrium are reduced in patients with 3-branch coronary artery disease without myocardial infarction; 2D-STE combined with RT-3DE is valuable in the evaluation of the right atrium in patients with coronary artery disease.
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Enfermedad de la Arteria Coronaria , Ecocardiografía Tridimensional , Atrios Cardíacos , Péptido Natriurético Encefálico , Humanos , Masculino , Ecocardiografía Tridimensional/métodos , Femenino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Péptido Natriurético Encefálico/sangre , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Anciano , Fragmentos de Péptidos/sangre , Función del Atrio Derecho/fisiología , Ecocardiografía/métodos , Angiografía Coronaria/métodosRESUMEN
Melatonin (MT), as a hormone regulating the rhythm of sleep, is widely used in health products. However, illicit and excessive use of MT might cause undesirable effects. Therefore, it is essential to establish highly sensitive and specific rapid methods for MT analysis in health products. In this study, we established indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and indirect competitive chemiluminescent enzyme immunoassay (ic-CLEIA) for sensitive and selective detection of MT in health products. Under optimal conditions, half-maximum inhibitory concentration (IC50 value) and limit of detection (LOD, IC10 value) for MT by ic-ELISA were 0.25 ng mL-1 and 0.03 ng mL-1 respectively, while the IC50 and LOD of ic-CLEIA were lower at 0.17 ng mL-1 and 0.03 ng mL-1 respectively. Three MT-free Chinese patent medicines were spiked with MT and the recovery rates ranged from 71.89% to 117% (ic-ELISA) and 83.66% to 107.17% (ic-CLEIA). The level of MT in six MT-containing health products was assessed in parallel using the developed methods and HPLC. Both ic-ELISA and ic-CLEIA showed good consistencies (R2 = 0.999 and 0.993, respectively) with HPLC, indicating that the two methods developed were sensitive, fast, and reliable for application in MT analysis.
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Melatonina , Mediciones Luminiscentes/métodos , Ensayo de Inmunoadsorción Enzimática/métodosRESUMEN
BACKGROUND: Paraneoplastic cerebellar degeneration (PCD), which is rare in clinical practice, is closely related to autoimmunity. Cases positive for anti-Yo antibodies (anti-Purkinje cytoplasmic antibody 1) are the main subtype of PCD. PCD is subacute cerebellar degeneration, and while it progresses over weeks to months, its resultant deficits last much longer. Cancer patients with anti-Yo antibody-positive PCD are very rare. Most of them are breast cancer or ovarian cancer patients but also occasionally lung cancer patients. CASE SUMMARY: A 61-year-old woman presented with sudden vertigo, nausea, and vomiting for approximately 10 d. The patient's neurological examination showed torsion with downbeat nystagmus and ataxia of the right limb and trunk. Laboratory examination found that the patient's cerebrospinal fluid and serum were anti-Yo antibody-positive, positron emission tomography computed tomography showed an increased metabolic rate in the retroperitoneal lymph nodes, and the pathology of lymph node punctures in the retroperitoneum and neck suggested adenocarcinoma of the pancreaticobiliary duct, which strengthens the hypothesis of paraneoplastic origin. Intravenous immunoglobulin (IVIg) 0.4 g/kg/d for 5 d and methylprednisolone 160 mg for 3 d were initiated, which was reduced to 80 mg for 3 d and then to 40 mg for 7 d. After treatment with IVIg and a steroid, the patient's vertigo and ataxia alleviated. CONCLUSION: The patient's vertigo and ataxia alleviated after treatment, suggesting that early immunotherapeutic intervention may have certain value in stopping neurological loss.
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Neuroinflammation is a common feature of age-related brain disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and cerebral ischemia. 5-lipoxygenase (5-LOX), a proinflammatory enzyme, modulates inflammation by generating leukotrienes. Abnormal activation of 5-LOX and excessive production of leukotrienes have been detected in the development of age-related brain pathology. In this review, we provide an update on the current understanding of 5-LOX activation and several groups of functionally related inhibitors. In addition, the modulatory roles of 5-LOX in the pathogenesis and progression of the age-related brain disorders have been comprehensively highlighted and discussed. Inhibition of 5-LOX activation may represent a promising therapeutic strategy for AD, PD and cerebral ischemia.
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Enfermedad de Alzheimer , Isquemia Encefálica , Araquidonato 5-Lipooxigenasa , Humanos , Inflamación , LeucotrienosRESUMEN
Neuroinflammation is a complex biological process and has been known to play an important role in age-related cerebrovascular and neurodegenerative disorders, such as cerebral ischemia, Alzheimer's disease, and Parkinson's disease. Cysteinyl leukotrienes (CysLTs) are potent inflammatory lipid mediators that exhibit actions mainly through activating type 1 and type 2 CysLT receptors (CysLT1 and CysLT2). Accumulating evidence shows that CysLT1 and CysLT2 are activated at different stages of pathological process in various cell types in the brain such as vascular endothelial cells, astrocytes, microglia, and neurons in response to insults. However, the precise roles and mechanisms of CysLT1 and CysLT2 in regulating the pathogenesis of cerebral ischemia, Alzheimer's disease, and Parkinson's disease are not fully understood. In this article, we focus on current advances that link activation of CysLT1 and CysLT2 to the pathological process during brain ischemia and neurodegeneration and discuss mechanisms by which CysLT1 and CysLT2 mediate inflammatory process and brain injury. Multitarget anti-inflammatory potentials of CysLT1 and CysLT2 antagonism for neuroinflammation and brain injury will also be reviewed.
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Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Encefalopatías/genética , Encefalopatías/patología , Isquemia Encefálica/genética , Isquemia Encefálica/patología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Receptores de Leucotrienos/metabolismo , Astrocitos/metabolismo , Células Endoteliales/metabolismo , Humanos , Inflamación , Microglía/metabolismo , Neuronas/metabolismoAsunto(s)
Angiomiolipoma , Carcinoma de Células Renales , Quiste Epidérmico , Hamartoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Hamartoma/diagnóstico , Errores Diagnósticos , Diagnóstico DiferencialAsunto(s)
Carcinoma de Células Renales , Eosinofilia , Neoplasias Renales , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/diagnóstico por imagen , Eosinofilia/patología , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , FemeninoAsunto(s)
Calcinosis , Recurrencia Local de Neoplasia , Humanos , Recurrencia Local de Neoplasia/cirugía , Calcinosis/cirugía , Calcinosis/patología , Calcinosis/diagnóstico por imagen , Fibroma/cirugía , Fibroma/patología , Femenino , Enfermedades del Pie/cirugía , Enfermedades del Pie/patología , Neoplasias de los Tejidos Blandos/cirugía , Neoplasias de los Tejidos Blandos/patología , Masculino , AdultoRESUMEN
Yuba is the skin formed at the surface during the heating of soymilk. The 3rd, 7th, and 11th films were evaluated for properties at different RH. At 39% RH, the 11th film had the lowest moisture, while the 3rd film had the highest moisture. However, at 75% RH, reverse moisture results were obtained. The tensile strengths of the 3rd and 11th films were highest at 15% moisture, whereas the tensile strength of the 7th film was highest at 25% moisture. Elongation of the 3rd (127%) and 11th (85%) films were highest at 25% moisture. The light transmittance of the films was low and opaque at 5% moisture. The films were transparent at 23%-28% moisture, but became opaque as the moisture increased. The films at 39% RH (ΔH, 113-203J/g) had higher thermal stability than those at 87% RH (ΔH, 315-493J/g). Moisture content markedly changed the yuba film properties.
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Fenómenos Mecánicos , Fenómenos Ópticos , Alimentos de Soja/análisis , Temperatura , Agua/análisisRESUMEN
OBJECTIVES: To assess the prevalence and related factors of benign paroxysmal positional vertigo (BPPV) in patients with spontaneous intracranial hypotension (SIH). METHODS: We retrospectively reviewed 156 consecutive inpatients with SIH, and collected the clinical and radiological data. These patients were divided into BPPV group and non-BPPV group according to the clinical manifestation and the results of Dix-Hallpike or supine roll tests during hospitalization period. We performed a univariate analysis and a further multiple logistic regression analysis to identify the related factors of the development of BPPV in SIH patients. RESULTS: BPPV was detected in 18 patients among the total 156 SIH patients (11.54%). The univariate analysis showed a low cerebrospinal fluid (CSF) pressure (P = 0.018), a small pontomesencephalic angle (P = 0.012) and a positive venous distension sign (VDS) (P = 0.045) were associated with the presence of BPPV. But the multivariate analysis only demonstrated a low CSF pressure was related to the presence of BPPV (OR = 1.022, 95% CI: 1.001-1.043, P = 0.044). CONCLUSION: BPPV is common in SIH patients. SIH patients with low CSF pressure may be prone to develop BPPV.
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Vértigo Posicional Paroxístico Benigno/etiología , Hipotensión Intracraneal/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Vértigo Posicional Paroxístico Benigno/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Hipotensión Intracraneal/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Adulto JovenRESUMEN
Neuroinflammation induced by microglial activation plays a critical role in many neurodegenerative diseases, including Parkinson's disease (PD). Recent studies have indicated that cysteinyl leukotriene receptor 2 (CysLT2R) is involved in inflammation and brain injury after cerebral ischemia. However, the role of CysLT2R in microglial responses associated with PD remains unclear. In the present study, we determined the regulatory roles of CysLT2R in microglial inflammation and subsequent neurotoxicity in an in vitro brain inflammation model induced by the microglial activator lipopolysaccharide (LPS). We found that LPS induced phagocytosis of a murine microglial cell line (BV-2 cells) and increased production of the proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). The expression of CysLT2R protein was up-regulated and the nuclear translocation of CysLT2R was induced in LPS-activated BV-2 cells. CysLT2R selective antagonist HAMI 3379 significantly inhibited LPS-induced phagocytosis and overproduction of the cytokines in BV-2 cells. Similarly, the CysLT2R silencing by specific short hairpin RNA (shRNA) had the same effects as those of HAMI 3379, suggesting that the effect might be CysLT2R-dependent. Furthermore, the conditioned medium (CM) derived from LPS-treated BV-2 cells induced the cell death of a rat adrenal pheochromocytoma cell line (PC12). HAMI 3379 and CysLT2R shRNA attenuated neuronal death by suppressing the production of neurotoxic cytokines released from LPS-activated microglia. Collectively, these results suggest that CysLT2R mediates LPS-induced microglial inflammation and consequent neurotoxicity. CysLT2R may be a promising molecular target that modulates microglia-related neuroinflammation in neurodegenerative disorders, such as PD.
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Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/toxicidad , Microglía/efectos de los fármacos , Receptores de Leucotrienos/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular Transformada/efectos de los fármacos , Ácidos Ciclohexanocarboxílicos/farmacología , Relación Dosis-Respuesta a Droga , Ratones , Fagocitosis/efectos de los fármacos , Ácidos Ftálicos/farmacología , ARN Interferente Pequeño/farmacología , Ratas , Receptores de Leucotrienos/genética , Factores de TiempoRESUMEN
The 5-lipoxygenase (5-LOX) products cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators. CysLTs mediate their biological actions through activating CysLT receptors (CysLT(1)R and CysLT(2)R). We have recently reported that 5-LOX and CysLT(1)R mediated PC12 cell injury induced by high concentrations of rotenone (0.3-10 µM), which was reduced by the selective 5-LOX inhibitor zileuton and CysLT(1)R antagonist montelukast. The purpose of this study was to examine the regulatory roles of the 5-LOX/CysLT(1)R pathway in microglial activation induced by low concentration rotenone. After mouse microglial BV2 cells were stimulated with rotenone (0.3-3 nM), phagocytosis and release of pro-inflammatory cytokine were assayed as indicators of microglial activation. We found that rotenone (1 and 3 nM) increased BV2 microglial phagocytosis and the release of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Zileuton and montelukast prevented rotenone (3 nM)-induced phagocytosis and cytokine release. Furthermore, rotenone significantly up-regulated 5-LOX expression, induced 5-LOX translocation to the nuclear envelope, and increased the production of CysLTs. These responses were inhibited by zileuton. Rotenone also increased CysLT(1)R expression and induced nuclear translocation of CysLT(1)R. In primary rat microglia, rotenone (10 nM) increased release of IL-1ß and TNF-α, whereas zileuton (0.1 µΜ) and montelukast (0.01 µΜ) significantly inhibited this response. These results indicated that 5-LOX and CysLT(1)R might be key regulators of microglial activation induced by low concentration of rotenone. Interference of 5-LOX/CysLT(1)R pathway may be an effective therapeutic strategy for microglial inflammation.