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Stroke is the most common cerebrovascular disease and one of the leading causes of death and disability worldwide. The current conventional treatment for stroke involves increasing cerebral blood flow and reducing neuronal damage; however, there are no particularly effective therapeutic strategies for rehabilitation after neuronal damage. Therefore, there is an urgent need to identify a novel alternative therapy for stroke. Acupuncture has been applied in China for 3000 years and has been widely utilized in the treatment of cerebrovascular diseases. Accumulating evidence has revealed that acupuncture holds promise as a potential therapeutic strategy for stroke. In our present review, we focused on elucidating the possible mechanisms of acupuncture in the treatment of ischemic stroke, including nerve regeneration after brain injury, inhibition of inflammation, increased cerebral blood flow, and subsequent rehabilitation.
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Lesiones Encefálicas , Isquemia Encefálica , Electroacupuntura , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/terapia , Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND: Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease. Liver transplantation (LT) is the most effective treatment. We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF. METHODS: This was an observational cohort study conducted between January 2018 and December 2020. Clinical characteristics, cirrhosis-related complications at LT and patient survival post-LT were collected. All liver recipients with ACLF were followed for 1 year post-LT. RESULTS: A total of 212 LT recipients with ACLF were enrolled, including 75 (35.4%) patients with ACLF-1, 64 (30.2%) with ACLF-2, and 73 (34.4%) with ACLF-3. The median waiting time for LT was 11 (4-24) days. The most prevalent cirrhosis-related complication was ascites (78.8%), followed by hepatic encephalopathy (57.1%), bacterial infections (48.1%), hepatorenal syndrome (22.2%) and gastrointestinal bleeding (11.3%). Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications (all P < 0.05). A simplified model was developed by assigning one point to each complication: transplantation for ACLF with cirrhosis-related complication (TACC) model. Risk stratification of TACC model identified 3 strata (≥ 4, = 3, and ≤ 2) with high, median and low risk of death after LT (P < 0.001). Moreover, the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models (chronic liver failure-consortium ACLF score, Chinese Group on the Study of Severe Hepatitis B-ACLF score, model for end-stage liver disease score and Child-Turcotte-Pugh score). CONCLUSIONS: The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF. The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival, which might help to determine transplant timing for ACLF.
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Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Humanos , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/cirugía , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/cirugía , Trasplante de Hígado/efectos adversos , PronósticoRESUMEN
Atherosclerosis (AS) is a disease dangerous to human health and the main pathological cause of ischemic cardiovascular diseases. Although its pathogenesis is not fully understood, numerous basic and clinical studies have shown that AS is a chronic inflammatory disease existing in all stages of atherogenesis. It may be a common link or pathway in the pathogenesis of multiple atherogenic factors. Inflammation is associated with AS complications, such as plaque rupture and ischemic cerebral infarction. In addition to inflammation, apoptosis plays an important role in AS. Apoptosis is a type of programmed cell death, and different apoptotic cells have different or even opposite roles in the process of AS. Unlike linear RNA, circular RNA (circRNA) a covalently closed circular non-coding RNA, is stable and can sponge miRNA, which can affect the stages of AS by regulating downstream pathways. Ultimately, circRNAs play very important roles in AS by regulating inflammation, apoptosis, and some other mechanisms. The study of circular RNAs can provide new ideas for the prediction, prevention, and treatment of AS.
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Aterosclerosis , Trastornos Cerebrovasculares , MicroARNs , Humanos , ARN Circular/genética , Aterosclerosis/genética , MicroARNs/genética , Apoptosis/genética , Proliferación Celular , Inflamación/genéticaRESUMEN
AIMS: The purpose of this study was to perform an assessment of circulating microRNAs (miRNAs) as promising biomarker for hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) through a meta-analysis. METHODS: A comprehensive literatures search extended up to March 1, 2020 in PubMed, Cochrane library, Embase, Web of Science, Scopus and Ovid databases. The collected data were analyzed by random-effects model, the pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were used to explore the diagnostic performance of circulating miRNAs. Meta-regression and subgroup analysis were further carried out to explore the heterogeneity. RESULTS: A total of 16 articles including 3606 HCV-HCC patients and 3387 HCV patients without HCC were collected. The pooled estimates indicated miRNAs could distinguish HCC patients from chronic hepatitis C (CHC) and HCV-associated liver cirrhosis (HCV-LC), with a SEN of 0.83 (95% CI, 0.79-0.87), a SPE of 0.77 (95% CI, 0.71-0.82), a DOR of 17 (95% CI, 12-28), and an AUC of 0.87 (95% CI, 0.84-0.90). The combination of miRNAs and AFP showed a better diagnostic accuracy than each alone. Subgroup analysis demonstrated that diagnostic accuracy of miRNAs was better for plasma types, up-regulated miRNAs, and miRNA clusters. There was no evidence of publication bias in Deeks' funnel plot. CONCLUSIONS: Circulating miRNAs, especially for miRNA clusters, have a relatively high diagnostic value for HCV-HCC from CHC and HCV-LC.
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Carcinoma Hepatocelular , MicroARN Circulante , Hepatitis C Crónica , Neoplasias Hepáticas , MicroARNs , Carcinoma Hepatocelular/diagnóstico , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Neoplasias Hepáticas/diagnóstico , MicroARNs/genéticaRESUMEN
The neurological diseases primarily include acute injuries, chronic neurodegeneration, and others (e.g., infectious diseases of the central nervous system). Autophagy is a housekeeping process responsible for the bulk degradation of misfolded protein aggregates and damaged organelles through the lysosomal machinery. Recent studies have suggested that autophagy, particularly selective autophagy, such as mitophagy, pexophagy, ER-phagy, ribophagy, lipophagy, etc., is closely implicated in neurological diseases. These forms of selective autophagy are controlled by a group of important proteins, including PTEN-induced kinase 1 (PINK1), Parkin, p62, optineurin (OPTN), neighbor of BRCA1 gene 1 (NBR1), and nuclear fragile X mental retardation-interacting protein 1 (NUFIP1). This review highlights the characteristics and underlying mechanisms of different types of selective autophagy, and their implications in various forms of neurological diseases.
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Autofagia/genética , Terapia Molecular Dirigida , Enfermedades del Sistema Nervioso/genética , Proteínas de Ciclo Celular/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de Transporte de Membrana/genética , Enfermedades del Sistema Nervioso/patología , Enfermedades del Sistema Nervioso/terapia , Proteínas Nucleares/genética , Proteínas Quinasas/genética , Proteínas de Unión al ARN/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor (TNF) superfamily which mainly induces apoptosis of tumour cells and transformed cell lines with no systemic toxicity, whereas they share high sequence homology with TNF and CD95L. These unique effects of TRAIL have made it an important molecule in oncology research. However, the research on TRAIL-related antineoplastic agents has lagged behind and has been limited by the extensive drug resistance in cancer cells. Given the several findings showing that TRAIL is involved in immune regulation and other pleiotropic biological effects in non-malignant cells, TRAIL and its receptors have attracted widespread attention from researchers. In the central nervous system (CNS), TRAIL is highly correlated with malignant tumours such as glioma and other non-neoplastic disorders such as acute brain injury, CNS infection and neurodegenerative disease. Many clinical and animal studies have revealed the dual roles of TRAIL in which it causes damage by inducing cell apoptosis, and confers protection by enhancing both pro- and non-apoptosis effects in different neurological disorders and at different sites or stages. Its pro-apoptotic effect produces a pro-survival effect that cannot be underestimated. This review extensively covers in vitro and in vivo experiments and clinical studies investigating TRAIL. It also provides a summary of the current knowledge on the TRAIL signalling pathway and its involvement in pathogenesis, diagnosis and therapeutics of CNS disorders as a basis for future research.
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Enfermedades Neurodegenerativas/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Animales , Investigación Biomédica , Humanos , Modelos Biológicos , Transducción de SeñalRESUMEN
Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. Despite its high prevalence, effective treatment strategies for TBI are limited. Traumatic brain injury induces structural and functional alterations of astrocytes, the most abundant cell type in the brain. As a way of coping with the trauma, astrocytes respond in diverse mechanisms that result in reactive astrogliosis. Astrocytes are involved in the physiopathologic mechanisms of TBI in an extensive and sophisticated manner. Notably, astrocytes have dual roles in TBI, and some astrocyte-derived factors have double and opposite properties. Thus, the suppression or promotion of reactive astrogliosis does not have a substantial curative effect. In contrast, selective stimulation of the beneficial astrocyte-derived molecules and simultaneous attenuation of the deleterious factors based on the spatiotemporal-environment can provide a promising astrocyte-targeting therapeutic strategy. In the current review, we describe for the first time the specific dual roles of astrocytes in neuronal plasticity and reconstruction, including neurogenesis, synaptogenesis, angiogenesis, repair of the blood-brain barrier, and glial scar formation after TBI. We have also classified astrocyte-derived factors depending on their neuroprotective and neurotoxic roles to design more appropriate targeted therapies. Video Abstract.
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Astrocitos , Lesiones Traumáticas del Encéfalo , Animales , Astrocitos/metabolismo , Astrocitos/patología , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/terapia , Humanos , NeurogénesisRESUMEN
BACKGROUND: COVID-19 is highly contagious, and the crude mortality rate could reach 49% in critical patients. Inflammation concerns on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. METHODS: In this cross-sectional study, 100 patients were included and divided into mild, severe or critical groups according to disease condition. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. RESULTS: Significantly, disease severity was associated with age (R = -0.564, P < 0.001), interleukin-2 receptor (IL2R) (R = -0.534, P < 0.001), interleukin-6 (IL-6) (R = -0.535, P < 0.001), interleukin-8 (IL-8) (R = -0.308, P < 0.001), interleukin-10 (IL-10) (R = -0.422, P < 0.001), tumor necrosis factor α (TNFα) (R = -0.322, P < 0.001), C-reactive protein (CRP) (R = -0.604, P < 0.001), ferroprotein (R = -0.508, P < 0.001), procalcitonin (R = -0.650, P < 0.001), white cell counts (WBC) (R = -0.54, P < 0.001), lymphocyte counts (LC) (R = 0.56, P < 0.001), neutrophil count (NC) (R = -0.585, P < 0.001) and eosinophil counts (EC) (R = 0.299, P < 0.001). With IL2R > 793.5 U/mL or CRP > 30.7 ng/mL, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. CONCLUSIONS: Inflammation is closely related to severity of COVID-19, and IL-6 and TNFα might be promising therapeutic targets.
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COVID-19/diagnóstico , Inflamación/complicaciones , Adulto , Anciano , Área Bajo la Curva , Proteína C-Reactiva/metabolismo , COVID-19/inmunología , Estudios Transversales , Femenino , Humanos , Inflamación/inmunología , Interleucina-10/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina/sangre , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVES: To compare the effects of intranasal dexmedetomidine (DEX) and DEX-ketamine (KET) on hemodynamics and sedation quality in children with congenital heart disease. DESIGN: A randomized controlled, double-blind, prospective trial. SETTING: A tertiary care teaching hospital. PARTICIPANTS: The study comprised 60 children undergoing transthoracic echocardiography (TTE). INTERVENTIONS: Patients were randomly allocated into the DEX group (group D [nâ¯=â¯30]) or the DEX-KET group (group D-K [nâ¯=â¯30]). Group D received 2 µg/kg of intranasal DEX; group D-K received 2 µg/kg of DEX and 1 mg/kg of KET intranasally. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in hemodynamics, measured using mean arterial pressure (MAP) and heart rate (HR). Secondary outcomes were onset time, wake-up time, and discharge time. No differences were found in mean arterial pressure or heart rate. The onset time was significantly shorter in group D-K than in group D (9.6 ± 2.9 minutes v 14.3 ± 3.4 minutes; pâ¯=â¯0.031). The wake-up time was longer in group D-K than in group D (52 ± 14.7 minutes v 39.6 ± 12.1 minutes; pâ¯=â¯0.017). The discharge time was longer in group D-K than in group D (61.33 ± 11.59 minutes v 48.17 ± 8.86 minutes; p < 0.001). No differences in hemodynamics were found between the 2 groups. Intranasal DEX was found to be as effective for TTE sedation as intranasal DEX-KET, with longer onset time and shorter recovery and discharge times. CONCLUSION: No differences in hemodynamics were found between the 2 groups. Intranasal DEX was found to be as effective for TTE sedation as is intranasal DEX-KET, with longer onset time and shorter recovery and discharge times.
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Dexmedetomidina , Cardiopatías Congénitas , Ketamina , Niño , Ecocardiografía , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/tratamiento farmacológico , Humanos , Hipnóticos y Sedantes , Estudios ProspectivosRESUMEN
Sleep disturbance is the most prominent symptom in depressive patients and was formerly regarded as a main secondary manifestation of depression. However, many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression among young, middle-aged and older adults. This bidirectional association between sleep disturbance and depression has created a new perspective that sleep problems are no longer an epiphenomenon of depression but a predictive prodromal symptom. In this review, we highlight the treatment of sleep disturbance before, during and after depression, which probably plays an important role in improving outcomes and preventing the recurrence of depression. In clinical practice, pharmacological therapies, including hypnotics and antidepressants, and non-pharmacological therapies are typically applied. A better understanding of the pathophysiological mechanisms between sleep disturbance and depression can help psychiatrists better manage this comorbidity.
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Depresión/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Antidepresivos/uso terapéutico , Depresión/complicaciones , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Hipnóticos y Sedantes/uso terapéutico , Factores de Riesgo , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/tratamiento farmacológicoRESUMEN
This publisher's note amends the author listing in Appl. Opt.58, 122 (2019)APOPAI0003-693510.1364/AO.58.000122.
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BACKGROUND: The relationship between vessel angulation and large changes in vessel geometry after stent implantation and the occurrence of stent failure still remains unclear. We sought to investigate the association of the change in the coronary bending angle after stenting and the risk for late stent failure by three-dimensional quantitative coronary angiography (3D QCA). METHODS: The bending angle in coronary lesions that presented with late stent failure and those without stent failure was computed during the cardiac cycle, before and after stenting using a recently developed 3D QCA software. RESULTS: A total of 40 lesions with stent failure (cases) were successfully matched to 47 lesions without stent failure (controls).The mean duration to follow-up coronary angiography was 1,011 days in cases and 1,109 days in the control group (P = 0.14). In stent failure, the systolic bending angle after stenting was smaller (14.45° [12.18, 17.68] versus 18.20° [14.00, 20.30], P = 0.01), while the stent-induced change in systolic bending angle was significantly larger (4.15° [1.13, 7.20] versus 1.80° [-1.90, 4.40], P = 0.004). Multivariable logistic regression analysis suggested that systolic bending angle after stenting (odds ratio: 0.88; 95% CI: 0.79-0.99; P = 0.03), and decrease in systolic bending angle after stenting (odds ratio: 1.13; 95% CI: 1.02-1.26; P = 0.03) were predictors of stent failure. CONCLUSIONS: Our study suggests that a change in the natural tortuous course of the coronaries by stent implantation with the decrease in coronary bending angle is a potentially major contributor in stent failure.
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Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Imagenología Tridimensional , Intervención Coronaria Percutánea/instrumentación , Falla de Prótesis , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: To reveal the serum proteomic profiling of intraductal carcinoma (IDC) patients in China, establish a serum proteome fractionation technique for choosing magnetic beads for proteomic analysis in breast cancer research; and identify differentially expressed peptides (m/z; P < 0.0001) as potential biomarkers of early IDCs. METHODS: We used two different kinds of magnetic beads (magnetic bead-based weak cation exchange chromatography (MB-WCX) and immobilized metal ion affinity chromatography (MB-IMAC-Cu)) to analyze 32 patients with early stage (stages I-II) IDC and 32 healthy control serum samples for proteomic profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The mass spectra, analyzed using ClinProTools software, distinguished between IDC patients and healthy individuals based on k-nearest neighbor genetic algorithm. RESULTS: The serum samples purified in the MB-WCX group provided better proteomic patterns than the MB-IMAC-Cu group. The samples purified by MB-WCX had better average peak numbers, higher peak intensities, and better capturing ability of low abundance proteins or peptides in serum samples. In addition, the MB-WCX and MB-IMAC-Cu purification methods, followed MALDI-TOF MS identification and use of ClinProTools software accurately distinguished patients with early stage IDC from healthy individuals. CONCLUSION: Serum proteomic profiling by MALDI-TOF MS is a novel potential tool for the clinical diagnosis of patients with IDC in China.
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Neoplasias de la Mama/sangre , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/sangre , Carcinoma Ductal de Mama/metabolismo , Fenómenos Magnéticos , Proteómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Adulto , Anciano , Biomarcadores de Tumor/sangre , Proteínas Sanguíneas/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Estudios de Casos y Controles , Fraccionamiento Químico , Cromatografía de Afinidad , Cromatografía por Intercambio Iónico , Femenino , Humanos , Microesferas , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Control de CalidadRESUMEN
BACKGROUND: MicroRNAs play important roles in the development and progression of various cancers. Recent studies have shown that miR-638 was downregulated in several tumors; however, its role in gastric cancer (GC) has not been investigated in detail. AIMS: The purpose of this study was to determine the role of miR-638 and to elucidate its regulatory mechanism in GC. METHODS: The expression levels of miR-638 and specificity protein 2 (Sp2) were detected by real-time PCR and Western blotting in GC. After pcDNA6.2-GW/EmGFP-miR-638 vector, miR-638 inhibitor and Sp2-siRNA transfection, the AGS cell proliferation was investigated by MTT assay and cell cycle, and apoptosis was detected using the Annexin V/PI. In addition, the regulation of Sp2 by miR-638 was evaluated by real-time RT-PCR, Western blot and luciferase reporter assays; cyclin D1 expression was measured by Western blotting. RESULTS: The expression of miR-638 is dramatically down-regulated and Sp2 expression is remarkably up-regulated in GC tissues. Luciferase assays revealed that miR-638 inhibited Sp2 expression by targeting the 3'-UTR of Sp2 mRNA. Overexpression of miR-638 and Sp2-siRNA reduced Sp2 expression at both the mRNA and protein levels in vitro, and inhibition of miR-638 increased Sp2 expression. Moreover, we found that miR-638 overexpression and Sp2-siRNA markedly suppressed cell proliferation with decreasing expression of cyclin D1 and inducing G1-phase cell-cycle arrest in vitro; inhibition of miR-638 significantly promoted cell proliferation by increasing expression of cyclin D1 and leading more cells into the S and G2/M phase. CONCLUSIONS: Our results demonstrated that miR-638 suppressed GC cell proliferation by targeting Sp2 with influence on the expression of cyclin D1. We suggest that miR-638 might be a candidate predictor or an anticancer therapeutic target for GC patients.
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MicroARNs/metabolismo , Factor de Transcripción Sp2/antagonistas & inhibidores , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Ciclina D1/antagonistas & inhibidores , Ciclina D1/genética , Ciclina D2/metabolismo , Regulación hacia Abajo/genética , Técnicas de Silenciamiento del Gen , Humanos , Factor de Transcripción Sp2/genética , Neoplasias Gástricas/patologíaRESUMEN
PURPOSE: The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in vivo pharmacokinetic properties.
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Inhibidores de Histona Desacetilasas/farmacocinética , Ácidos Hidroxámicos/farmacocinética , Hierro/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Área Bajo la Curva , Línea Celular Tumoral , Liberación de Fármacos , Femenino , Semivida , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Liposomas , Masculino , Tamaño de la Partícula , Fagocitos/metabolismo , Polietilenglicoles/química , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Ratas , Ratas Sprague-Dawley , Solubilidad , VorinostatRESUMEN
Astragaloside IV, one of the main effective components isolated from Astragalus membranaceus, has multiple neuroprotective properties, while the effects of astragaloside IV on the attenuation of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) and its possible mechanisms are unknown. In the present study, we aimed to determine whether astragaloside IV could inhibit oxidative stress, reduce neuronal apoptosis, and improve neurological deficits after experimental SAH in rats. Rats (n=68) were randomly divided into the following groups: Sham group, SAH group, SAH+vehicle group, and SAH+astragaloside IV group. Astragaloside IV or an equal volume of vehicle was administered at 1 h and 6 h after SAH, all the rats were subsequently sacrificed at 24 h after SAH. Mortality, neurological scores, and brain edema were assessed, biochemical tests and histological studies were also performed at that point. SAH induced an increase in the malondialdehyde (MDA) level, neuronal apoptosis, cleaved caspase 3, brain edema and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Astragaloside IV treatment reversed these changes and improved neurobehavioral outcomes of SAH rats. Our findings suggested that astragaloside IV may alleviate EBI after SAH through antioxidative and anti-apoptotic effects.
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Lesiones Encefálicas/tratamiento farmacológico , Saponinas/uso terapéutico , Hemorragia Subaracnoidea/tratamiento farmacológico , Triterpenos/uso terapéutico , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/mortalidadRESUMEN
Fullerene-based amphiphiles are able to form bilayer vesicles in aqueous solution. In this study, the self-assembly behavior of polymer-tethered nanoballs (NBs) with nonpolar/polar/nonpolar (n-p-n') motif in a selective solvent is investigated by dissipative particle dynamics. A model NB bears two hydrophobic polymeric arms (n'-part) tethered on an extremely hydrophobic NB (n-part) with hydrophilic patch (p-part) patterned on its surface. Dependent on the hydrophobicity and length of tethered arms, three types of aggregates are exhibited, including NB vesicle, core-shell micelle, and segmented-worm. NB vesicles are developed for a wide range of hydrophobic arm lengths. The presence of tethered arms perturbs the bilayer structure formed by NBs. The structural properties including the order parameter, membrane thickness, and area density of the inner leaflet decrease with increasing the arm length. These results indicate that for NBs with longer arms, the extent of interdigitation in the membrane rises so that the overcrowded arms in the inner corona are relaxed. The transport and mechanical properties are evaluated as well. As the arm length grows, the permeability increases significantly because the steric bulk of tethered arms loosens the packing of NBs. By contrast, the membrane tension decreases owing to the reduction of NB/solvent contacts by the polymer corona. Although fusion can reduce membrane tension, NB vesicles show strong resistance to fusion. Moreover, the size-dependent behavior observed in small liposomes is not significant for NB vesicles due to isotropic geometry of NB. Our simulation results are consistent with the experimental findings.
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Coloides/química , Fulerenos/química , Modelos Químicos , Modelos Moleculares , Nanosferas/química , Nanosferas/ultraestructura , Agua/química , Simulación por Computador , Interacciones Hidrofóbicas e Hidrofílicas , Conformación Molecular , Electricidad EstáticaRESUMEN
The coordination between carrier and active metal is critical to the catalytic efficiency of ammonia borane (AB) hydrolysis reaction. In the present study, we report a new type of catalytic support based on molybdenum boride (MBene) MoAl1-xB and demonstrate that the effective combination of MoAl1-xB with Ru nanoparticles can realize the significantly enhanced performance for hydrogen generation. Owing to the efficient activation and dissociation of reactants, the optimal Ru/MoAl1-xB catalyst achieves the large turnover frequency of 494 molH2 molRu-1 min-1, high hydrogen generation rate of 119817 mL min-1 gRu-1 and favorable apparent activation energy of 39.2 kJ mol-1 for the catalytic hydrolysis of AB under alkaline-free condition. The isotopic test suggests the cleavage of OH bond in H2O is the rate-determining step for hydrolysis reaction, while the fracture of B-H bond in AB is also well revealed by attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy. Significantly, the flexible on-demand hydrogen generation is achieved by using chemical switches for on-off AB hydrolysis. This study provides a new support platform based on two-dimensional MBene to exploit efficient catalysts to boost AB dehydrogenation.
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Objective: This study aimed to compare the clinical outcomes of double kissing mini-culotte (DKMC) stenting with those of mini-culotte (MC) stenting in treating patients with true coronary bifurcation lesions (CBLs) in the clinical real world. Methods: This retrospective observational cohort study included 180 consecutive patients with true CBLs (Medina type 1,1,1; 1,0,1; 0,1,1). All eligible patients underwent coronary angiography and percutaneous coronary intervention with two-stent techniques in our hospital; among them, 97 received DKMC treatment and 83 MC treatment. The primary clinical endpoints were the major adverse cardiovascular events (MACE), which included cardiac death, myocardial infarction, and target vessel/lesion revascularization (TVR/TLR). The secondary endpoints were stent thrombosis, in-stent restenosis, and individual components of MACE. Results: Quantitative coronary angiography analysis (at 5 years) revealed that late lumen loss (0.25 ± 0.41â mm vs. 0.14 ± 0.32â mm, P = 0.032) and segmental diameter restenosis of the side branch (27.84 ± 12.34% vs. 19.23 ± 9.76%, P = 0.016) were lower in the DKMC treatment group than that in the MC treatment group. Notably, compared to that in the MC treatment group, the cumulative event rate of MACE at 5 years (22.8% vs. 8.3%, P = 0.007) and TVR/TLR (17.7% vs. 6.3%, P = 0.018) was higher in the DKMC treatment group, driven mainly by TVR/TLR. Especially, the DKMC group was related to a significant reduction in the primary and secondary endpoints in high-risk patients. Conclusion: DKMC treatment was associated with less late lumen loss and restenosis in the side branch and a lower rate of cumulative MACE and TVR/TLR. DKMC treatment is more effective for treating true CBLs than MC treatment; however, these findings warrant further confirmation through a randomized clinical trial.
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Controversy surrounds the role of serum uric acid and whether treatment intervention is favorable in retarding the progression of chronic kidney disease (CKD). The association of serum uric acid levels and CKD patient mortality risk needs to be further determined by large sample cohort studies. The National Health and Nutrition Examination Survey participants with CKD from 1998 to 2017 were enrolled in the study. Multivariable Cox regression models were used to reveal the association of serum uric acid concentrations and CKD mortality risks. A total of 9891 CKD patients were enrolled in the study, and 3698 individuals died during the follow-up. Increasing serum uric acid levels are independently relevant to higher mortality risks of CKD patients (HR per SD increase). A restricted cubic spline curve showed a nonlinear association between serum uric acid and CKD mortality risks (p for nonlinearity = 0.046). CKD patients with higher levels of serum uric acid (≥ 5.900 mg/dL) show a significant increase in mortality risks (HR = 1.102, 95% CI 1.043-1.165). Sensitivity analysis demonstrated that the results were stable and robust. High serum uric acid levels (≥ 5.900 mg/dL) may be associated with increased mortality risks in CKD patients.