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1.
Exp Ther Med ; 25(6): 253, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37153896

RESUMEN

The majority of low-grade gliomas (LGGs) in adults invariably progress to glioblastoma over time. Spectrin ß non-erythrocytic 2 (SPTBN2) is detected in numerous tumors and is involved in tumor occurrence and metastasis. However, the specific roles and detailed mechanisms of SPTBN2 in LGG are largely unknown. The present study performed pan-cancer analysis for the expression and prognosis of SPTBN2 in LGG using The Cancer Genome Atlas and The Genotype-Tissue Expression. Western blotting was used to detect the amount of SPTBN2 between glioma tissues and normal brain tissues. Subsequently, based on expression, prognosis, correlation and immune infiltration, non-coding RNAs (ncRNAs) were identified that regulated SPTBN2 expression. Finally, tumor immune infiltrates associated with SPTBN2 and prognosis were performed. Lower expression of SPTBN2 was correlated with an unfavorable outcome in LGG. A significant correlation between the low SPTBN2 mRNA expression and poor clinicopathological features was observed, including wild-type isocitrate dehydrogenase status (P<0.001), 1p/19q non-codeletion (P<0.001) and elders (P=0.019). The western blotting results revealed that, compared with normal brain tissues, the amount of SPTBN2 was significantly lower in LGG tissues (P=0.0266). Higher expression of five microRNAs (miRs/miRNAs), including hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa-miR-34c-5p and hsa-miR-424-5p, correlated with poor prognosis by targeting SPTBN2 in LGG. Subsequently, four long ncRNAs (lncRNAs) [ARMCX5-GPRASP2, BASP1-antisense RNA 1 (AS1), EPB41L4A-AS1 and LINC00641] were observed in the regulation of SPTBN2 via five miRNAs. Moreover, the expression of SPTBN2 was significantly correlated with tumor immune infiltration, immune checkpoint expression and biomarkers of immune cells. In conclusion, SPTBN2 was lowly expressed and correlated with an unfavorable prognosis in LGG. A total of six miRNAs and four lncRNAs were identified as being able to modulate SPTBN2 in a lncRNA-miRNA-mRNA network of LGG. Furthermore, the current findings also indicated that SPTBN2 possessed anti-tumor roles by regulating tumor immune infiltration and immune checkpoint expression.

2.
Front Chem ; 9: 767847, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34778216

RESUMEN

Bacterial infection is a major threat to human health. However, many antibacterial agents currently used are severely limited due to drug-resistance, and the development of side effects. Herein, we have developed a non-antibiotic nanocomposite consisting of chitosan (ChS) coated silver nanoparticles (AgNPs) and graphene nanoribbon (GNR)-based nanowires for light-triggered eradication of bacteria. The presence of AgNP/ChS significantly enhanced the interactions of the GNR nanowires with Pseudomonas aeruginosa, a clinically common Gram-negative bacterium. Which enables the highly effective photothermal eradication of bacteria by GNR upon near-infrared light irradiation. The nanocomposite was shown to be applicable for the light-triggered eradication of bacterial biofilms and the inhibition of bacterial growth on medical patches used for abdominal-wall hernia surgery.

3.
Chem Sci ; 12(33): 11089-11097, 2021 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-34522306

RESUMEN

Triple negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer. Here, we report the construction of graphene nanoribbon (GNR)-based supramolecular ensembles with dual-receptor (mannose and αvß3 integrin receptors) targeting function, denoted as GNR-Man/PRGD, for targeted photothermal treatment (PTT) of TNBC. The GNR-Man/PRGD ensembles were constructed through the solution-based self-assembly of mannose-grafted GNRs (GNR-Man) with a pyrene-tagged αvß3 integrin ligand (PRGD). Enhanced PTT efficacies were achieved both in vitro and in vivo compared to that of the non-targeting equivalents. Tumor-bearing live mice were administered (tail vein) with GNR-Man/PRGD and then each mice group was subjected to PTT. Remarkably, GNR-Man/PRGD induced complete ablation of the solid tumors, and no tumor regrowth was observed over a period of 15 days. This study demonstrates a new and promising platform for the development of photothermal nanomaterials for targeted tumor therapy.

4.
J Dig Dis ; 22(2): 83-90, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33314672

RESUMEN

OBJECTIVES: Behçet's disease (BD) is a chronic inflammatory disease characterized by recurrent oral aphthous ulcers, intestinal lesions, genital ulcers, uveitis, and skin lesions. Evidence regarding mucosal healing for the prognosis of intestinal BD is scarce. The aim of this systematic review and meta-analysis was to determine the association between mucosal healing and long-term outcomes of patients with intestinal BD. METHODS: Relevant studies were identified in a comprehensive search of PubMed, Cochrane Library, and EMBASE databases. Studies reporting long-term outcomes of mucosal healing in patients with intestinal BD were included. Pooled risk ratio (RR) and 95% confidence interval (CI) for disease recurrence and surgery were calculated using the Mantel-Haenszel random-effects models. Heterogeneity among the eligible studies was evaluated using the Q test and I2 statistics. RESULTS: Of the 4785 studies initially identified, 8 were finally included. The pooled RR for the association between mucosal healing and disease recurrence was 0.41 (95% CI 0.30-0.57, P < 0.001). For the association between mucosal healing and the risk of surgery, the pooled RR was 0.33 (95% CI 0.17-0.63, P < 0.001). Confounding factors were adjusted in one study, whereas other studies only reported a crude association between mucosal healing and long-term outcomes without adjustment. CONCLUSIONS: Mucosal healing is associated with a decreased risk of recurrence and surgery in intestinal BD. However, more studies are required given a small number of currently eligible studies and insufficient adjustment for confounding factors.


Asunto(s)
Síndrome de Behçet , Enfermedades Intestinales , Humanos , Intestinos , Pronóstico , Estomatitis Aftosa
5.
Chem Sci ; 13(1): 247-256, 2021 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-35059174

RESUMEN

Glycosidases, which are the enzymes responsible for the removal of residual monosaccharides from glycoconjugates, are involved in many different biological and pathological events. The ability to detect sensitively the activity and spatiotemporal distribution of glycosidases in cells will provide useful tools for disease diagnosis. However, the currently developed fluorogenic probes for glycosidases are generally based on the glycosylation of the phenol group of a donor-acceptor type fluorogen. This molecular scaffold has potential drawbacks in terms of substrate scope, sensitivity because of aggregation-caused quenching (ACQ), and the inability for long-term cell tracking. Here, we developed glycoclusters characterized by aggregation-induced emission (AIE) properties as a general platform for the sensing of a variety of glycosidases. To overcome the low chemical reactivity associated with phenol glycosylation, here we developed an AIE-based scaffold, which is composed of tetraphenylethylene conjugated with dicyanomethylene-4H-pyran (TPE-DCM) with a red fluorescence emission. Subsequently, a pair of dendritic linkages was introduced to both sides of the fluorophore, to which six copies of monosaccharides (d-glucose, d-galactose or l-fucose) were introduced through azide-alkyne click chemistry. The resulting AIE-active glycoclusters were shown to be capable of (1) fluorogenic sensing of a diverse range of glycosidases including ß-d-galactosidase, ß-d-glucosidase and α-l-fucosidase through the AIE mechanism, (2) fluorescence imaging of the endogenous glycosidase activities in healthy and cancer cells, and during cell senescence, and (3) glycosidase-activated, long-term imaging of cells. The present study provides a general strategy to the functional, in situ imaging of glycosidase activities through the multivalent display of sugar epitopes of interest onto properly designed AIE-active fluorogens.

6.
Onco Targets Ther ; 13: 11139-11149, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33154653

RESUMEN

OBJECTIVE: The aim of this study was to investigate the effect of the tumor-associated macrophage-m2-cancer cell complex (TAM-M2-CC) on the heterostructural modification of lung adenocarcinoma. METHODS: The expression of CD163+/CD68+ in macrophages in the microenvironment of 161 cases of lung adenocarcinoma was identified by dual immunohistochemistry, and the association between a TAM-M2-CC and its growth, as well as the histological changes in lung adenocarcinoma cells, was assessed. RESULTS: The morphological change of lung adenocarcinoma was related to the number of m2 phenotypes of the macrophages in the microenvironment of lung adenocarcinoma. TAM-M2-CCs were involved in the process of cancer cell recognition, association, and reconstruction. CONCLUSION: The microenvironment of lung adenocarcinoma can affect the phenotypic distinction of macrophages, and the polarization recruitment, zombification, and formation of a TAM-M2-CC, which can also affect the local differentiation of lung adenocarcinoma to a certain extent. The applicable pathogenesis needs to be verified and studied further.

7.
Chem Commun (Camb) ; 56(43): 5735-5738, 2020 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-32323669

RESUMEN

We report on a supramolecular sensor array using fluorogenic peptide probes and graphene oxide that can target glycoproteins on a viral caspid, facilitating the differentiation of ebola virus from marburg virus and receptor-extensive vesicular stomatitis virus using principal component analysis.


Asunto(s)
Técnicas Biosensibles , Proteínas de la Cápside/química , Ebolavirus/aislamiento & purificación , Colorantes Fluorescentes/química , Glicoproteínas/química , Grafito/química , Péptidos/química , Marburgvirus/aislamiento & purificación , Vesiculovirus/aislamiento & purificación
8.
Mol Carcinog ; 59(5): 545-556, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32149414

RESUMEN

Colorectal cancer (CRC) is a common malignancy. Many reports have implicated aberrant mitochondrial activity in the progression of CRC, with particular emphasis on the dysregulation of redox signaling and oxidative stress. In this study, we focused on manganese superoxide dismutase (MnSOD/SOD2), a key antioxidant enzyme, which maintains intracellular redox homeostasis. Current literature presents conflicting mechanisms for how SOD2 influences tumorigenesis and tumor progression. Here, we explored the role of SOD2 in CRC specifically. We found high levels of SOD2 expression in CRC tissues. We carried out a series of experiments to determine whether knockdown of SOD2 expression in CRC cell lines would reverse features of tumorigenesis. We found that reduced SOD2 expression decreased cell proliferation, migration, and invasion activity in CRC cells. Results from an additional series of experiments on mitochondrial function implicated a dual role for SOD2 in promoting CRC progression. First, proper level of SOD2 helped CRC cells maintain mitochondrial function by disposal of superoxide (O2.- ). Second, over-expression of SOD2 induced H2 O2 -mediated tumorigenesis by upregulating AMPK and glycolysis. Our results indicate that SOD2 may promote the occurrence and development of CRC by regulating the energy metabolism mediated by AMPK signaling pathways.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Transformación Celular Neoplásica/patología , Neoplasias Colorrectales/patología , Metabolismo Energético , Mitocondrias/patología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Movimiento Celular , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Glucólisis , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Pronóstico , Superóxido Dismutasa/genética , Células Tumorales Cultivadas
9.
Chem Soc Rev ; 49(2): 593-641, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31915764

RESUMEN

Glycoconjugates and their applications as lectin ligands in biology have been thoroughly investigated in the past decades. Meanwhile, the intrinsic properties of such multivalent molecules were limited essentially to their ability to bind to their receptors with high selectivity and/or avidity. The present review will focus on multivalent glycoconjugates displaying an additional capability such as fluorescence properties not only for applications toward imaging of cancer cells and detection of proteins or pathogens but also for drug delivery systems toward targeted cancer therapy. This review is a collection of research articles discussed in the context of the structural features of fluorescent glycoconjugates organized according to their fluorescent core scaffold and with their representative applications.


Asunto(s)
Colorantes Fluorescentes/química , Glicoconjugados/química , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Fluorescencia , Humanos , Neoplasias/tratamiento farmacológico
10.
Chem Commun (Camb) ; 56(4): 664, 2020 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-31848536

RESUMEN

Correction for 'Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material' by Wei-Tao Dou et al., Chem. Commun., 2019, 55, 13235-13238.

11.
Angew Chem Int Ed Engl ; 59(9): 3658-3664, 2020 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-31868285

RESUMEN

With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self-assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one-dimensional wire-like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual-modal properties with significant reactive-oxygen-species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram-positive, Gram-negative, and drug-resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual-modal antimicrobial agents that are able to overcome antibiotic resistance.


Asunto(s)
Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Luz , Nanocompuestos/química , Antiinfecciosos/química , Bacterias Gramnegativas/efectos de los fármacos , Grafito/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Nanocompuestos/toxicidad , Nanotubos/química , Polietilenglicoles/química , Porfirinas/química , Especies Reactivas de Oxígeno/metabolismo
12.
Chem Commun (Camb) ; 55(88): 13235-13238, 2019 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-31621698

RESUMEN

Protein C receptor (PROCR) is a recently discovered transmembrane biomarker for several tissue stem cells and is highly expressed in triple-negative breast cancer (TNBC) patient-derived xenografts. Herein, to enrich the toolbox for the biochemical evaluation of PROCR, we have developed a peptide-functionalized fluorogenic 2D material based on the self-assembly between a fluorescent peptide probe and thin-layer molybdenum disulfide. The material developed was suitable for the sensitive detection of PROCR recombinant protein in buffer solution and the fluorescence imaging of TNBC cells that express high levels of PROCR.


Asunto(s)
Biomarcadores de Tumor/análisis , Receptor de Proteína C Endotelial/análisis , Colorantes Fluorescentes/química , Imagen Óptica , Péptidos/química , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Línea Celular Tumoral , Femenino , Humanos , Células MCF-7 , Estructura Molecular , Tamaño de la Partícula , Espectrometría de Fluorescencia , Propiedades de Superficie
13.
Neurocrit Care ; 31(3): 501-506, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31161421

RESUMEN

BACKGROUND AND OBJECTIVE: The aim of the study is to investigate the value of serum iron and hemoglobin levels for predicting acute seizures following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Clinical and laboratorial data from patients with ruptured intracranial aneurysms were collected in the retrospective study. Age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, serum potassium, sodium, calcium, phosphorus, and iron were collected. Acute seizures were determined as seizures within 1 week following aSAH. Propensity score matching (PSM) analyses were performed to correct imbalances in patient characteristics between seizure and non-seizure groups. RESULTS: A total of 760 patients were included. Incidence of acute seizures following aSAH was 6.4%. In the univariate analysis, significant differences were detected in age, admission Hunt-Hess grade, Fisher grade, hemoglobin, serum sodium, and serum iron between seizure and non-seizure groups. In multivariate logistic regression model, lower serum iron was considered as a risk factor for acute seizures (OR 0.182, 95% CI 0.084-0.393, p = 0.000), as well as lower hemoglobin (OR 0.977, 95% CI 0.962-0.993, p = 0.004) and higher serum sodium (OR 1.072, 95% CI 1.003-1.145, p = 0.039). After PSM, there were no significant differences in age, admission Hunt-Hess grade, Fisher grade, and serum sodium between seizure and non-seizure groups. The matched seizure group had lower serum iron and hemoglobin levels compared with the matched non-seizure group (p < 0.05). The optimal cutoff value for serum iron and hemoglobin levels as a predictor of acute seizure after aSAH was determined as 9.9 mmol/L (sensitivity was 81.63% and the specificity was 65.40%) and 119 g/L (sensitivity was 63.27% and the specificity was 70.18%), respectively. CONCLUSIONS: Serum iron and hemoglobin levels were inversely associated with a high risk of acute seizures following aSAH.


Asunto(s)
Anemia Ferropénica/sangre , Hemoglobinas/metabolismo , Hierro/sangre , Convulsiones/sangre , Hemorragia Subaracnoidea/sangre , Adulto , Anemia/sangre , Anemia/epidemiología , Anemia Ferropénica/epidemiología , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Rotura Espontánea , Convulsiones/epidemiología , Convulsiones/etiología , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/fisiopatología
14.
ACS Appl Mater Interfaces ; 11(25): 22181-22187, 2019 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-31150201

RESUMEN

Triple-negative breast cancer (TNBC) is a devastating disease worldwide, for which targeted imaging and therapeutic agents remain elusive. There has been growing awareness that carbohydrates are valuable as drug candidates and targeting agents for a variety of human diseases, including cancers that overexpress carbohydrate receptors on the cell surface. Here, we develop a two-dimensional (2D) glycocluster by means of simple, stepwise self-assembly for the targeted delivery of theranostic agents to TNBC cells that express mannose receptors (MRs) on the cell surface. Human serum albumin, which contains a variety of hydrophobic pockets capable of accommodating small molecules, was used to simultaneously encapsulate a mannose-based glycoprobe and a commercial photosensitizer (i.e., Ce6). The multicomponent "neoglycoprotein" formed was used to self-assemble with 2D MnO2, producing 2D glycoclusters, which could be selectively internalized by a TNBC cell line (MDA-MB-231) as facilitated by binding to the transmembrane MR. The intracellular degradation of the 2D MnO2 backbone by biothiols then released Ce6 for cell imaging and, subsequently, photodynamic therapy. This study provides insights into the development of carbohydrate-based materials for targeted, stimuli-responsive theranostics of TNBC.


Asunto(s)
Nanomedicina Teranóstica/métodos , Neoplasias de la Mama Triple Negativas/metabolismo , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Femenino , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Receptor de Manosa , Lectinas de Unión a Manosa/genética , Lectinas de Unión a Manosa/metabolismo , Fotoquimioterapia/métodos , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Espectrometría de Fluorescencia/métodos
15.
World Neurosurg ; 122: e561-e568, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-31108072

RESUMEN

OBJECTIVE: We tested the hypothesis that cerebellopontine angle (CPA) tumors are associated with a greater incidence of unruptured intracranial aneurysms (IAs). METHODS: Patients with intracranial tumors (ITs) undergoing computed tomography angiography and magnetic resonance imaging were enrolled in an observational cohort study that prospectively collected age, sex, hypertension, diabetes, cerebral arteriosclerosis, tumor type, tumor location, hydrocephalus, smoking, alcohol intake, CPA tumor size, cerebral aneurysms, and cerebral arteriosclerosis. Patients with the coexistence of IA and ITwere classified as group II, whereas the others with IT as group I. RESULTS: We included 1218 patients with IT for analysis. The incidence of IA was 7.1% (86/1218). A total of 31% of patients with aneurysms had CPA tumors. In a multivariate logistic regression model, a greater incidence of IA was found in female patients (odds ratio [OR] 1.726, 95% confidence interval [CI] 1.050-2.836, P=0.031) and in patients with CPA tumors (OR 3.002, 95% CI 1.822-4.947, P=0.000) after adjustment for tumor type, cerebral arteriosclerosis, and age. In female patients, CPA tumors were a unique independent risk factor of a greater incidence of IA (OR 2.270, 95% CI 1.194-4.317, P=0.012). Furthermore, cerebral arteriosclerosis was a unique independent risk factor of IA in patients with CPA tumors (OR 7.626, 95% CI 2.928-19.860, P=0.000). CONCLUSIONS: These data support the hypothesis that CPA tumors are associated with a greater incidence of unruptured IAs, especially in female patients. Cerebral arteriosclerosis contributed to elevated risk of IA in patients with CPA tumors.


Asunto(s)
Neoplasias Encefálicas/complicaciones , Aneurisma Intracraneal/etiología , Neuroma Acústico/complicaciones , Adenoma/complicaciones , Angiografía por Tomografía Computarizada , Femenino , Glioma/complicaciones , Humanos , Arteriosclerosis Intracraneal/complicaciones , Angiografía por Resonancia Magnética , Masculino , Neoplasias Meníngeas/complicaciones , Meningioma/complicaciones , Persona de Mediana Edad , Imagen Multimodal , Neoplasias Hipofisarias/complicaciones , Estudios Prospectivos , Factores de Riesgo
16.
World Neurosurg ; 126: e907-e913, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30872197

RESUMEN

OBJECTIVE: We tested the hypothesis that low serum iron levels are associated with acute hydrocephalus following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients presenting with ruptured intracranial aneurysms were enrolled in the prospective observational study. Age, sex, history of diabetes, hypertension and hyperlipidemia, symptom onset, Fisher grade, Hunt-Hess grade, aneurysm location, hemoglobin, and serum iron were collected. Acute hydrocephalus was determined within 72 hours after subarachnoid hemorrhage. A propensity-score matching analysis was performed to correct imbalances in patient characteristics between hydrocephalus and non-hydrocephalus groups. RESULTS: A total of 535 patients were included. Incidence of acute hydrocephalus was 20.0%. In multivariate logistic regression analysis, lower serum iron was considered as a risk factor of acute hydrocephalus, as well as delayed ischemic neurologic deficit and lower hemoglobin (P = 0.000). After propensity-score matching, lower serum iron was considered as an independent risk factor for acute hydrocephalus, whereas hemoglobin and delayed ischemic neurologic deficit were not. The matched hydrocephalus group had lower serum iron comparing with the matched non-hydrocephalus group (10.26 ± 5.33 mmol/L vs. 13.44 ± 5.18 mmol/L; P = 0.000). The optimal cut-off value for serum iron levels as a predictor for acute hydrocephalus in patients with aSAH was determined as 13.1 mmol/L in the receiver operating characteristic curve. Furthermore, lower serum iron levels (odds ratio 0.305; 95% confidence interval, 0.178-0.524; P = 0.000) and acute hydrocephalus (odds ratio 0.372; 95% confidence interval, 0.202-0.684; P = 0.001) were predictors of poor outcome, as well as higher Hunt-Hess grade and Fisher grade. CONCLUSIONS: Lower serum iron levels after aSAH was a predictor of acute hydrocephalus and unfavorable outcome.


Asunto(s)
Hidrocefalia/etiología , Hierro/sangre , Hemorragia Subaracnoidea/complicaciones , Adulto , Anciano , Femenino , Humanos , Hidrocefalia/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/sangre
17.
ACS Appl Bio Mater ; 2(11): 4904-4910, 2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-35021490

RESUMEN

Currently, chemotherapy is a widely used and important treatment for cancer. However, almost all of the treatments have shortcomings associated with poor specificity and high toxicity, which results in severe side effects to normal cells and tissue. This is a very important problem, and yet, it currently remains unanswered. Therefore, the development of the method for the more effective delivery of anticancer drugs to their targets and real-time monitoring of the localization of the drugs are very important. Herein, we designed a theranostic prodrug: CPT-p-Leu, which was constructed using fluorescent camptothecin (CPT), a self-immolative linker and leucine (Leu) residue. Upon exposure to LAP (leucine aminopeptidase: LAP), the amide bond in CPT-p-Leu will be cleaved, followed by an intramolecular 1,6-elimination, which triggers the active anticancer drug (CPT) release and recovers the fluorescence of CPT. With our design, the anticancer drug, CPT, can be used as both a drug and a fluorescence reporter, making our system suitable to accurately and effectively track the released CPT distribution. Based on this strategy, CPT-p-Leu could achieve the chemoselective detection of LAP and monitoring of the anticancer drug release. Furthermore, it also provides a very convenient way to accurately determine the location of the released drug in living samples. In addition, CPT-p-Leu shows a good cell membrane permeability and enhanced cytotoxicity toward LAP overexpressing cancer cells. We anticipate that our research will facilitate the development of improved theranostic systems for cancer therapy.

18.
World Neurosurg ; 120: e984-e990, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30196170

RESUMEN

OBJECTIVE: To determine whether extended lesionectomy is needed for patients with cerebral cavernous malformations presenting with epilepsy as compared with lesionectomy. METHODS: A literature search of PubMed, Embase, Web of Science, Clinical Trials and Cochrane Central Register of Controlled Trials was performed for pertinent English-language studies from 1967 to 2017. Eligible studies were selected according to uniform inclusion and exclusion criteria. RESULTS: Seven studies including 245 patients (107 receiving extended lesionectomy, 138 receiving lesionectomy) were selected. Meta-analysis and subgroup analyses were conducted to compare extended lesionectomy with lesionectomy. Pooled analysis demonstrated that seizure outcome was not statistically significantly improved in patients who underwent extended lesionectomy compared with lesionectomy (odds ratio = 0.77; 95% confidence interval, 0.39-1.51; P = 0.44; I2 = 15%). CONCLUSIONS: Extended lesionectomy does not contribute to better seizure control for patients with cerebral cavernous malformations with epilepsy. Resection of the lesion and surrounding hemosiderin is sufficient for patients with cerebral cavernous malformations presenting with epilepsy.


Asunto(s)
Epilepsia/complicaciones , Epilepsia/cirugía , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Procedimientos Neuroquirúrgicos , Humanos , Procedimientos Neuroquirúrgicos/métodos
19.
World Neurosurg ; 118: e500-e504, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30257302

RESUMEN

BACKGROUND AND OBJECTIVE: We tested the hypothesis that ionized calcium levels at admission are associated with early hematoma expansion and functional outcome in patients with hypertensive intracerebral hemorrhage (HICH). METHODS: Patients presenting with HICH were enrolled in the observational cohort study that prospectively collected age, sex, blood pressure, history of diabetes and smoking, time from symptom onset to initial computed tomography (CT), admission ionized calcium (iCa) and total calcium (tCa), coagulation function, Glasgow Coma Scale (GCS), and postoperative modified Rankin Scale score. Hematoma reconstruction on CT was performed to measure hematoma volumes. Hematoma expansion (HE) was defined as an increase of more than 30% or 6 mL in HICH volume. We performed univariate and multivariate analyses to assess for association of iCa level with early HE and functional outcome. RESULTS: We included 111 patients with HICH for analysis. Admission serum iCa was 1.10 mmol/L in patients with HE and 1.17 in patients without HE. Univariate analysis indicated significant difference of GCS, initial HICH volume, iCa, and tCa between the HE and non-HE groups (P < 0.05). Lower admission iCa (less than 1.12 mmol/L) was associated with HE (odds ratio [OR] 0.300, 95% confidence interval [CI] 0.095-0.951, P = 0.041) after adjustment for age, blood pressure, GCS score, time to initial CT scan, baseline HICH volume, prothrombin time, and tCa. Furthermore, predictive factors of poor outcome included iCa (OR 0.192, 95% CI 0.067-0.554, P = 0.002) and GCS score (OR 0.832, 95% CI 0.722-0.959, P = 0.011). CONCLUSIONS: These data support the hypothesis that lower ionized calcium is associated with early hematoma expansion and poor outcome in patients with hypertensive intracerebral hemorrhage.


Asunto(s)
Calcio/sangre , Hematoma/sangre , Hematoma/diagnóstico por imagen , Hemorragia Intracraneal Hipertensiva/sangre , Hemorragia Intracraneal Hipertensiva/diagnóstico por imagen , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
20.
Sci Rep ; 8(1): 5799, 2018 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-29643435

RESUMEN

It is not fully established whether leukocyte can predict the poor outcome for ruptured cerebral aneurysms (CA) or not. Here, we retrospectively analyzed the clinical data of 428 patients with ruptured CA between 2010 and 2015. Patients' demographic data, including gender, age, history of smoking, alcohol, hypertension, diabetes and hypercholesterolemia, Hunt-Hess and Fisher grade, occurrence of hydrocephalus, aneurysm location, time to surgery, delayed ischemic neurological deficit (DIND) and peak leukocyte of blood test from day 1 to 3 after aneurysmal rupture were recorded and analyzed. In the multivariable analysis model, gender, Fisher grade, time to surgery and hydrocephalus were not relevant to poor outcome. However, Hunt-Hess grade, DIND and preoperative leukocyte count (>13.84 × 109/L) were significantly associated with adverse outcome. The respective increased risks were 5.2- (OR5.24, 95% CI 1.67-16.50, p = 0.005), 6.2-(OR 6.24, 95% CI 3.55-10.99, p < 0.001) and 10.9-fold (OR 9.35, 95% CI 5.98-19.97, p < 0.001). The study revealed that Hunt-Hess grade, DIND and preoperative leukocyte count (>13.84 × 109/L) were independent risk factors for poor outcome of ruptured CA at 3 months. Higher leukocyte count is a convenient and useful marker to predict 3-month poor outcome for ruptured CA.


Asunto(s)
Técnicas de Apoyo para la Decisión , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico , Recuento de Leucocitos , Rotura/diagnóstico , Rotura/patología , Adulto , Anciano , Femenino , Humanos , Aneurisma Intracraneal/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
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