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1.
Phytomedicine ; 128: 155489, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38569295

RESUMEN

BACKGROUND AND PURPOSE: Atherosclerosis is the primary pathological basis of cardiovascular disease. Ferroptosis is a regulated form of cell death, a process of lipid peroxidation driven by iron, which can initiate and promote atherosclerosis. STAT6 is a signal transducer that shows a potential role in regulating ferroptosis, but, the exact role in ferroptosis during atherogenesis remains unclear. The Traditional Chinese Medicine Maijitong granule (MJT) is used for treating cardiovascular disease and shows a potential inhibitory effect on ferroptosis. However, the antiatherogenic effect and the underlying mechanism remain unclear. In this study, we determined the role of STAT6 in ferroptosis during atherogenesis, investigated the antiatherogenic effect of MJT, and determined whether its antiatherogenic effect was dependent on the inhibition of ferroptosis. METHODS: 8-week-old male LDLR-/- mice were fed a high-fat diet (HFD) at 1st and 10th week, respectively, to assess the preventive and therapeutic effects of MJT on atherosclerosis and ferroptosis. Simultaneously, the anti-ferroptotic effects and mechanism of MJT were determined by evaluating the expression of genes responsible for lipid peroxidation and iron metabolism. Subsequently, we reanalyzed microarray data in the GSE28117 obtained from cells after STAT6 knockdown or overexpression and analyzed the correlation between STAT6 and ferroptosis. Finally, the STAT6-/- mice were fed HFD and injected with AAV-PCSK9 to validate the role of STAT6 in ferroptosis during atherogenesis and revealed the antiatherogenic and anti-ferroptotic effect of MJT. RESULTS: MJT attenuated atherosclerosis by reducing plaque lesion area and enhancing plaque stability in both preventive and therapeutic groups. MJT reduced inflammation via suppressing inflammatory cytokines and inhibited foam cell formation by lowering the LDL level and promoting ABCA1/G1-mediated lipid efflux. MJT ameliorated the ferroptosis by reducing lipid peroxidation and iron dysregulation during atherogenesis. Mechanistically, STAT6 negatively regulated ferroptosis by transcriptionally suppressing SOCS1/p53 and DMT1 pathways. MJT suppressed the DMT1 and SOCS1/p53 via stimulating STAT6 phosphorylation. In addition, STAT6 knockout exacerbated atherosclerosis and ferroptosis, which abolished the antiatherogenic and anti-ferroptotic effects of MJT. CONCLUSION: STAT6 acts as a negative regulator of ferroptosis and atherosclerosis via transcriptionally suppressing DMT1 and SOCS1 expression and MJT attenuates atherosclerosis and ferroptosis by activating the STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways, which indicated that STAT6 acts a novel promising therapeutic target to ameliorate atherosclerosis by inhibiting ferroptosis and MJT can serve as a new therapy for atherosclerosis treatment.


Asunto(s)
Aterosclerosis , Proteínas de Transporte de Catión , Medicamentos Herbarios Chinos , Ferroptosis , Factor de Transcripción STAT6 , Proteína 1 Supresora de la Señalización de Citocinas , Animales , Ferroptosis/efectos de los fármacos , Aterosclerosis/tratamiento farmacológico , Factor de Transcripción STAT6/metabolismo , Masculino , Medicamentos Herbarios Chinos/farmacología , Ratones , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Transducción de Señal/efectos de los fármacos , Receptores de LDL/metabolismo , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Ratones Noqueados
2.
Front Endocrinol (Lausanne) ; 14: 1180415, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37670880

RESUMEN

Background and Purpose: Nonproliferative diabetic retinopathy (NPDR) occurs in the early stages of Diabetic retinopathy (DR), and the study of its metabolic markers will help to prevent DR. Hence, we aimed to establish a risk score based on multiple metabolites through untargeted metabolomic analysis of venous blood from NPDR patients and diabetic non-DR patients. Experimental Approach: Untargeted metabolomics of venous blood samples from patients with NPDR, diabetes melitus without DR were performed using high-performance liquid chromatography-mass spectrometry. Results: Detailed metabolomic evaluation showed distinct clusters of metabolites in plasma samples from patients with NPDR and diabetic non-DR patients. NPDR patients had significantly higher levels of phenylacetylglycine, L-aspartic acid, tiglylglycine, and 3-sulfinato-L-alaninate, and lower level of indolelactic acid, threonic acid, L-arginine (Arg), and 4-dodecylbenzenesulfonic acid compared to control. The expression profiles of these eight NPDR risk-related characteristic metabolites were analyzed using Cox regression to establish a risk score model. Subsequently, univariate and multivariate Cox regression analyses were used to determine that this risk score model was a predictor of independent prognosis for NPDR. Conclusions: Untargeted metabolome analysis of blood metabolites revealed unreported metabolic alterations in NPDR patients compared with those in diabetic non-DR patients or MH. In the venous blood, we identified depleted metabolites thA and Arg, indicating that they might play a role in NPDR development.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Humanos , Metabolómica , Factores de Riesgo , Metaboloma , Arginina
4.
Opt Lett ; 48(4): 888-891, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36790967

RESUMEN

Helicity-resolved Raman spectroscopy (HRRS) can effectively distinguish the Raman modes of two-dimensional (2D) layered materials by phonon symmetry. In this paper, we systematically investigated the phonon helicity selection of basal and edge planes of MoS2 bulk by HRRS. We find that the symmetry of the crystal structure changes the helicity selection of the E1g, E1 2g, and A1g modes in the edge plane. The theoretical calculation results confirm that the E1 2g and A1g modes of the basal plane exhibit a perfect helicity exchange, and the helicity selections of the E1 2g and A1g modes of the edge plane are eliminated or weakened. Our study provides references for phonon helicity selection of 2D layered materials represented by MoS2.

5.
Artículo en Inglés | MEDLINE | ID: mdl-36578267

RESUMEN

Asthma is a common pulmonary disease mainly caused by the infiltration of neutrophils. There is a limit to the therapeutic effects of the available asthma drugs on neutrophilic asthma. Shegan Mahuang Decoction (SMD) is one of the representative traditional Chinese medicine (TCM) prescriptions for asthma, and it can effectively relieve the clinical symptoms of patients. However, the effect of SMD on the treatment of neutrophilic asthma remains unknown. In this study, a mouse model of neutrophilic asthma induced by lipopolysaccharide (LPS)/ovalbumin (OVA) was established, and the effect of a modified SMD prescription on the model was evaluated. After treatment, SMD was demonstrated to be therapeutically effective on asthmatic mice via airway resistance detection and lung pathology and was able to affect cytokine levels in vivo. Further experiments verified that SMD regulated the expression of mitochondrial function proteins in bronchoalveolar lavage fluid (BALF) exosomes. The results demonstrate that SMD confers a therapeutic effect on a neutrophilic asthma mouse model, and it may reduce neutrophil airway inflammation by regulating myeloid-derived regulatory cell (MDRC) function and airway exosome mitochondrial function.

6.
Opt Express ; 30(21): 38492-38502, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36258413

RESUMEN

Study of exciton recombination process is of great significance for the optoelectronic device applications of two-dimensional transition metal chalcogenides (TMDCs). This research investigated the decoupling MoS2 structures by photoluminescence (PL) measurements. First, PL intensity of the bilayer MoS2 (BLM) is about twice of that of the single layer MoS2 (SLM) at low temperature, indicating no transition from direct bandgap to indirect bandgap for BLM due to the decrease of interlayer coupling which can be shown by Raman spectra. Then, the localized exciton emission appears for SLM at 7 K but none for BLM, showing different exciton localization characteristics. The PL evolution with respect to the excitation intensity and the temperature further reveal the filling, interaction, and the redistribution among free exciton states and localized exciton states. These results provide very useful information for understanding the localized states and carrier dynamics in BLM and SLM.

7.
ACS Appl Mater Interfaces ; 14(16): 19012-19022, 2022 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-35421305

RESUMEN

Recently, two-dimensional (2D) van der Waals heterostructures (vdWHs) have exhibited emergent electronic and optical properties due to their peculiar phonons and excitons, which lay the foundation for the development of photoelectronic devices. The dielectric environment plays an important role in the interlayer coupling of vdWHs. Here, we studied the interlayer and extra-layer dielectric effects on phonon and exciton properties in WS2/MoS2 and MoS2/WS2 vdWHs by Raman and photoluminescence (PL) spectroscopy. The ultralow frequency (ULF) Raman modes are insensitive to atomic arrangement at the interface between 1LW and 1LM and dielectric environments of neighboring materials, and the layer breathing mode (LBM) frequency follows that of WS2. The shift of high-frequency (HF) Raman modes is attributable to interlayer dielectric screening and charge transfer effects. Furthermore, the energy of interlayer coupling exciton peak I is insensitive to atomic arrangement at the interface between 1LW and 1LM and its energy follows that of MoS2, but the slight intensity difference in inversion vdWHs means that the substrate's dielectric properties may induce doping on the bottom layer. This paper provides fundamental understanding of phonon and exciton properties of such artificially formed vdWHs structures, which is important for new insights into manipulating the performances of potential devices.

8.
Travel Med Infect Dis ; 46: 102267, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35091118

RESUMEN

Human rabies is a serious public health problem that can't be ignored. Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP). However, current PEP relies on RIG purified from pooled human or equine plasma, which are either in chronic shortage or associated with safety concerns. Monoclonal antibodies have become widely accepted as safer and more cost-effective alternatives to RIG products in recent years. Here, we assessed the neutralization breadth of human monoclonal antibody ormutivimab and its protective efficacy in PEP models. Ormutivimab was able to neutralize a broad panel of Chinese prevalent street RABVs with neutralizing potency form 198-1487.6 IU/mL. Furthermore, ormutivimab offered comparable protection to that with HRIG both at standard doses (20 IU/kg) and higher doses (100 IU/kg and 200 IU/kg). The interference of ormutivimab on vaccine potency was also analyzed and found slightly reduced neutralizing antibody titers similar to HRIG. The broad-spectrum neutralization activities, highly protective potency, and rapid onset of action make ormutivimab an effective candidate for human rabies PEP.


Asunto(s)
Vacunas Antirrábicas , Virus de la Rabia , Rabia , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales , Caballos , Humanos , Modelos Animales , Profilaxis Posexposición , Rabia/prevención & control
9.
Opt Express ; 29(21): 32818-32825, 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34809104

RESUMEN

Angle-resolved polarized (ARP) Raman spectroscopy can be utilized to characterize the Raman modes of two-dimensional layered materials based on crystal symmetry or crystal orientation. In this paper, the polarization properties of E 1 2g and A1g modes on the basal plane and edge plane of high purity 2H-MoS2 bulk crystal grown by chemical vapor transport (CVT) method were investigated by ARP Raman spectroscopy. The I and II type ARP Raman spectroscopy with four kinds of polarization configurations: αY, αX, ßY, and ßX were used to explore the intensity dependence of E 1 2g and A1g modes at different planes on the polarization direction of incident/scattered light. The results show that the E 1 2g and A1g modes exhibit different polarization properties dependent on the polarization of the incident laser and the in-plane rotation of the sample at different planes. The experimental results were confirmed and analyzed through theoretical calculation. Our work sheds light on the intriguing effect of the subtle atomic structure in stacked MoS2 layers on the resulting ARP Raman properties. This provides a reference for the study of other two-dimensional layered crystalline materials by ARP Raman spectroscopy.

10.
Front Immunol ; 12: 608723, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33643312

RESUMEN

Objective: Posner-Schlossman syndrome (PSS), also known as glaucomatocyclitic crisis, is an ocular condition characterized by recurrent attacks of anterior uveitis and raised intraocular pressure. Previous studies by our team and others have identified the genetic association of complement pathway genes with uveitis and glaucoma. This study aimed to investigate the complement genes in PSS patients with the view of elucidating the genetic background of the disease. Methods: A total of 331 subjects (56 PSS patients and 275 controls) were recruited for this study. We selected 27 variants in six complement pathway genes (SERPING1, C2, CFB, CFH, C3, and C5) and detected them using TaqMan single nucleotide polymorphism (SNP) Genotyping Assays. Univariate SNP association analysis, haplotype-based association analysis, gene-gene interaction analysis among complement genes, and genotype-phenotype correlation analysis were performed. Results: Among the 27 variants of six complement pathway genes, the functional variant I62V (rs800292) at the CFH gene was found to be significantly associated with PSS; there was a significant increase in the frequency of A allele and AA homozygosity in PSS patients than in controls (P = 1.79 × 10-4; odds ratio (OR) 2.18, 95% CI: 1.44-3.29; P = 4.65 × 10-4; OR 3.66, 95% CI: 1.70-7.85, respectively). The additive effect of CFH-rs800292 and SERPING1-rs3824988 was identified with an OR of 12.50 (95% CI: 2.16-72.28). Genotype-phenotype analysis indicated that the rs800292 AA genotype was associated with a higher intraocular pressure and higher frequency of recurrence. Unlike a high proportion of human leukocyte antigen (HLA)-B27 positivity in anterior uveitis, only 3 in 56 (5.36%) PSS patients were HLA-B27 positive. In addition, one haplotype block (GC) in the SERPING1 gene showed a nominal association with PSS with an increased risk of 2.04 (P = 0.01; 95% CI: 1.18-3.53), but the P-value could not withstand the Bonferroni correction (Pcorr > 0.05). Conclusion: This study revealed a genetic association of a CFH variant with PSS as well as its clinical parameters, implying that the alternative complement pathway might play an important role in the pathogenesis of PSS. Further studies to enrich the understanding of the genetic background of PSS and the role of the complement system in ocular inflammation are warranted.


Asunto(s)
Alelos , Enfermedades Hereditarias del Ojo/diagnóstico , Enfermedades Hereditarias del Ojo/genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Factor H de Complemento/genética , Epistasis Genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo
11.
Front Cell Dev Biol ; 9: 616835, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33748106

RESUMEN

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism required for cleavage and polyadenylation (CPA) of the 3' untranslated region (3' UTR) of mRNAs. Several aberrant APA events have been reported in hepatocellular carcinoma (HCC). However, the regulatory mechanisms underlying APA remain unclear. In this study, we found that the expression of cleavage and polyadenylation specific factor 1 (CPSF1), a major component of the CPA complex, was significantly increased in HCC tissues and correlated with unfavorable survival outcomes. Knockdown of CPSF1 inhibited HCC cell proliferation and migration, whereas overexpression of CPSF1 caused the opposite effect. Based on integrative analysis of Iso-Seq and RNA-seq data from HepG2.2.15 cells, we identified a series of transcripts with differential 3' UTR lengths following the knockdown of CPSF1. These transcripts were related to the biological functions of gene transcription, cytoskeleton maintenance, and endomembrane system transportation. Moreover, knockdown of CPSF1 induced an increase in alternative splicing (AS) events in addition to APA. Taken together, this study provides new insights into our understanding of the post-transcriptional regulatory mechanisms in HCC and implies that CPSF1 may be a potential prognostic biomarker and therapeutic target for HCC.

12.
Front Pharmacol ; 12: 811897, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35153764

RESUMEN

Diabetic retinopathy (DR) is a complication of diabetes that has a serious impact on the quality of life of patients. VEGFA is necessary in the physiological state to maintain endothelial activity and physical properties of blood vessels. VEGFA plays an important role in the promotion of neovascularization; therefore, inhibition of VEGFA can degrade the structure of blood vessels and reduce neovascularization. In the present study, HERB, a high-throughput experimental and reference-oriented database of herbal medicines, was used for compound mining targeting VEGFA. The compounds most likely to interact with VEGFA were screened by molecular docking. Next, the compounds were used to verify whether it could inhibit the activity of the VEGF signaling pathway in vitro and neovascularization in vivo. In vitro, we found that dioscin could inhibit the activation of the VEGFA-VEGFR2 signaling pathway and cell proliferation of human retinal microvascular endothelial cells in a high-glucose (HG) environment. A more important dioscin intervention inhibits the expression of pro-angiogenic factors in the retinas of db/db mice. In conclusion, our study indicates that dioscin reduces the vascular damage and the expression of pro-angiogenic factors in the retina of db/db mice and implies an important and potential application of dioscin for treatment of DR in clinics.

13.
J Hepatol ; 74(4): 838-849, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33212090

RESUMEN

BACKGROUND & AIMS: Little is known about Epstein-Barr virus (EBV)-associated intrahepatic cholangiocarcinoma (EBVaICC) because of its rarity. We aimed to comprehensively investigate the clinicopathology, tumor immune microenvironment (TIME) and genomic landscape of this entity in southern China. METHODS: We evaluated 303 intrahepatic cholangiocarcinomas (ICCs) using in situ hybridization for EBV. We compared clinicopathological parameters between EBVaICC and nonEBVaICC, and we analyzed EBV infection status, tumor-infiltrating lymphocytes (TILs) and genomic features of EBVaICC by immunohistochemistry, double staining, nested PCR, multiplex immunofluorescence staining, fluorescence in situ hybridization and whole-exome sequencing. RESULTS: EBVaICC accounted for 6.6% of ICCs and was associated with EBV latency type I infection and clonal EBV isolates. Patients with EBVaICC were more often female and younger, with solitary tumors, higher HBV infection rates and less frequent cirrhosis; the lymphoepithelioma-like (LEL) subtype was more common in EBVaICC. EBVaICC was associated with a significantly larger TIME component than nonEBVaICC. The LEL subtype of EBVaICC - associated with a significantly increased density and proportion of CD20+ B cells and CD8+ T cells - was associated with significantly higher 2-year survival rates than conventional EBVaICC and nonEBVaICC. Both PD-1 and PD-L1 in TILs, and PD-L1 in tumor cells, were overexpressed in EBVaICC. High PD-L1 expression in tumor cells and high CD8+ TIL densities were significantly more common in EBVaICC than in nonEBVaICC. Seven genes (MUC4, DNAH1, GLI2, LIPE, MYH7, RP11-766F14.2 and WDR36) were mutated in at least 3 patients. EBVaICC had a different mutational pattern to liver fluke-associated cholangiocarcinoma and HBV-associated ICC. CONCLUSIONS: EBVaICC, as a subset of ICC, has unique etiological, clinicopathological and genetic characteristics, with a significantly larger TIME component. Paradoxically, patients with EBVaICC could be candidates for immune checkpoint therapy. LAY SUMMARY: Epstein-Barr virus (EBV) is associated with a subtype of intrahepatic cholangiocarcinoma, with unique clinicopathological and genetic characteristics. The tumor immune microenvironment is also different in this tumor subtype and patients with EBV-associated intrahepatic cholangiocarcinoma may respond well to immune checkpoint inhibitors.


Asunto(s)
Antígeno B7-H1/genética , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Inhibidores de Puntos de Control Inmunológico , Receptor de Muerte Celular Programada 1/genética , Microambiente Tumoral/inmunología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Linfocitos T CD8-positivos/patología , China/epidemiología , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inhibidores de Puntos de Control Inmunológico/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunohistoquímica , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Secuenciación del Exoma/métodos
14.
Theranostics ; 10(20): 9186-9199, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32802186

RESUMEN

Metabolism reprogramming is a hallmark of many cancer types. We focused on clear cell renal carcinoma (ccRCC) which is characterized by its clear and glycogen-enriched cytoplasm with unknown reasons. The aim of this study was to identify the clinical significance, biological function, and molecular regulation of glycogen synthase 1 (GYS1) in ccRCC glycogen accumulation and tumor progression. Methods: We determined the clinical relevance of GYS1 and glycogen in ccRCC by immunohistochemistry and periodic acid-schiff staining in fresh tissue and by tissue micro-array. Metabolic profiling with GYS1 depletion was performed by metabolomics analysis. In vitro and xenograft mouse models were used to evaluate the impact of GYS1 on cell proliferation. High-throughput RNA-Seq analyses and co-immunoprecipitation-linked mass spectrometry were used to investigate the downstream targets of GYS1. Flow cytometry and CCK8 assays were performed to determine the effect of GYS1 and sunitinib on cell viability. Results: We observed that GYS1 was significantly overexpressed and glycogen was accumulated in ccRCC tissues. These effects were correlated with unfavorable patient survival. Silencing of GYS1 induced metabolomic perturbation manifested by a carbohydrate metabolism shift. Overexpression of GYS1 promoted tumor growth whereas its silencing suppressed it by activating the canonical NF-κB pathway. The indirect interaction between GYS1 and NF-κB was intermediated by RPS27A, which facilitated the phosphorylation and nuclear import of p65. Moreover, silencing of GYS1 increased the synthetic lethality of ccRCC cells to sunitinib treatment by concomitantly suppressing p65. Conclusions: Our study findings reveal an oncogenic role for GYS1 in cell proliferation and glycogen metabolism in ccRCC. Re-sensitization of ccRCC cells to sunitinib suggests that GYS1 is a useful indicator of unfavorable prognosis as well as a therapeutic target for patients with ccRCC.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Glucógeno Sintasa/metabolismo , Glucógeno/metabolismo , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , FN-kappa B/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/fisiología , Progresión de la Enfermedad , Humanos , Inmunohistoquímica/métodos , Masculino , Metaboloma/fisiología , Ratones , Ratones Endogámicos BALB C , Pronóstico , Transducción de Señal/fisiología
15.
World Neurosurg ; 135: e738-e747, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31899397

RESUMEN

BACKGROUND: Despite evidence that a greater extent of resection (EOR) improves survival, the role of extended resection based on magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) in the prognosis of glioblastoma (GBM) remains controversial. This study aims to investigate the role of additional resection of FLAIR-detected abnormalities and its influence on clinical outcomes of patients with GBM. METHODS: Forty-six patients with newly diagnosed GBM involving eloquent brain areas were included. Surgeries were performed using awake craniotomy (AC) or AC combined with sodium fluorescein (SF) guidance. Following total removal of the contrast-enhancing tumor area, the EOR of FLAIR abnormalities was dichotomized to identify the best separation threshold for progression-free survival (PFS), overall survival (OS), and 30-day postoperative neurologic function of patients with GBM. RESULTS: The threshold for removal of FLAIR abnormalities affecting survival was determined to be 25%. The median OS and PFS were shorter in the group with FLAIR resection <25% compared with the group with FLAIR resection ≥25% (12 months vs. 26 months; P = 0.001 and 6 months vs. 15 months; P = 0.016, respectively). Univariate and multivariate analyses identified tumor location within or near the eloquent brain areas and the 25% threshold for FLAIR EOR as independent factors affecting OS and PFS. CONCLUSIONS: Identifying a feasible threshold for the resection of FLAIR abnormalities is valuable in improving the survival of patients with GBM. Extended resection of GBM involving eloquent brain areas was safe when using a combination of AC and SF-guided surgery.


Asunto(s)
Neoplasias Encefálicas/cirugía , Craneotomía/métodos , Glioblastoma/cirugía , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Craneotomía/mortalidad , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Estado de Ejecución de Karnofsky , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Carga Tumoral , Vigilia , Adulto Joven
16.
World J Clin Cases ; 8(24): 6243-6251, 2020 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-33392305

RESUMEN

BACKGROUND: Coats disease is an idiopathic exudative outer retinopathy caused by abnormal retinal vascular development. AIM: To evaluate the long-term outcomes of intravitreal conbercept injection with laser photocoagulation as a treatment for Coats disease in adults. METHODS: This retrospective case series study included patients diagnosed with Coats disease and treated with intravitreal conbercept injection and 532-nm laser photocoagulation at the Ophthalmology Department of Shenzhen People's Hospital between January 2016 and January 2017. Best-corrected visual acuity (BCVA) measurements, noncontact tonometry, ophthalmoscopy, fundus photography, fundus fluorescein angiography and optical coherence tomography were performed before treatment and at 1 wk, 1 mo, 3 mo, 6 mo, 9 mo, 12 mo, 24 mo and 36 mo after therapy. Best-corrected visual acuity was measured using the early treatment of diabetic retinopathy study chart. RESULTS: The study included eight eyes of 8 patients (7 men) aged 36.10 ± 6.65 years. The average BCVA of the affected eye before treatment was 51.17 ± 15.15 letters (range, 28-70 letters), and the average central macular thickness was 303.30 ± 107.87 µm (range, 221-673 µm). Four eyes were injected once, three were injected twice, and one was injected three times. Average follow-up duration was 37.33 ± 2.26 mo. Average BCVA of the affected eye was 51.17 ± 15.15 letters before treatment and was increased by 13.50 ± 3.20, 16.25 ± 7.73, 18.25 ± 8.96, 18.03 ± 5.27, 18.63 ± 3.35, 19.75 ± 6.96, 18.05 ± 5.36 and 17.88 ± 3.45 letters at 1 wk, 1 mo, 3 mo, 6 mo, 9 mo, 12 mo, 24 mo and 36 mo after treatment, respectively (P < 0.01). The patients showed varying degrees of subretinal fluid resorption after treatment. None of the patients had serious complications such as increased intraocular pressure, development/progression of cataracts, endophthalmitis or retinal detachment. CONCLUSION: Intravitreal injection of conbercept combined with 532-nm laser photocoagulation may be a feasible treatment for Coats disease in adult patients.

17.
Huan Jing Ke Xue ; 40(5): 2341-2348, 2019 May 08.
Artículo en Chino | MEDLINE | ID: mdl-31087875

RESUMEN

The anaerobic ammonium oxidation(ANAMMOX) granular sludge in the EGSB reactor was divided into three groups according to particle size, which were R1 (0.5-1.4 mm), R2 (1.4-2.8 mm), and R3 (>2.8 mm). Extracellular polymeric substances (EPS) of different sizes from ANAMMOX granular sludge were extracted, and the EPS characteristics and their influence on the surface characteristics of ANAMMOX aggregates were analyzed. With the increased particle size of ANAMMOX granular sludge, the PS content was between (10.69±0.11)-(12.28±0.15) mg·g-1, while the PN content increased from (56.88±0.86) mg·g-1 to (98.59±2.10) mg·g-1, and PN/PS increased from 5.32 to 9.05. The EPS functional groups and the content of three-dimensional fluorescent components of different size ANAMMOX granular sludge were different. As the granular sludge size increased, the value of α-helix/(ß-sheet + random coil) gradually decreased from 0.60 to 0.43, which is beneficial to the hydrophobicity expression of the sludge. Due to the increased particle size of the granular sludge, the hydrophobicity of the sludge surface increased from 54.2% to 63.1%, and the Zeta potential increased from -41.2 mV to -31.5 mV. The increased hydrophobicity and surface charge are beneficial to the formation of sludge aggregates. EPS can enhance ANAMMOX sludge hydrophobicity and increase Zeta potential. The presence of PN in EPS is essential to this process.

18.
Chemosphere ; 210: 366-375, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30015127

RESUMEN

Bacterial surface properties fundamentally affect the stability and aggregation of anammox granular sludge. The variation in the surface properties of the granular sludge at different salinities were investigated to further clarify the effect of salinity on the aggregation of anammox granular sludge in this study. High anammox activity was obtained at a salinity of 30 g/L NaCl, and the average removal efficiency of NH4+N, NO2--N and TN reached 91.9% ±â€¯1.4%, 97.3% ±â€¯0.4% and 86.3% ±â€¯0.9%, respectively. The sludge particle size in Reactor 1 (with 0 g/L NaCl as control) and Reactor 2 (with 0, 15 and 30 g/L NaCl) increased from 1.62 ±â€¯0.16 mm and 1.59 ±â€¯0.12 mm to 2.71 ±â€¯0.23 mm and 2.44 ±â€¯0.19 mm, respectively, during total operation. PN gradually decreased from 30.58 ±â€¯2.5 mg/g to 18.11 ±â€¯2.1 mg/g, and PS sharply increased from 1.48 ±â€¯0.09 mg/g to 10.52 ±â€¯0.50 mg/g with the increase in salinity. The PS/PN ratio of extracellular polymeric substances (EPS) rapidly increased from 0.05 to 0.58 with an increase of salinity. Fourier transform infra-red spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) results showed that salinity inhibited the expression of anammox sludge hydrophobicity by changing surface groups. Binding between multivalent metal ions and EPS was significantly hindered by the high Na+ concentration. The results of this study provided a better understanding of the effect of salinity on the stability and aggregation of anammox granular sludge in saline wastewater treatment.


Asunto(s)
Salinidad , Aguas del Alcantarillado/química , Aguas Residuales/química , Bacterias/metabolismo , Reactores Biológicos/microbiología , Nitrógeno/aislamiento & purificación , Tamaño de la Partícula , Polímeros/química , Propiedades de Superficie
19.
Chem Commun (Camb) ; 54(40): 5074-5077, 2018 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-29707730

RESUMEN

A novel, hydrophilic and recyclable methoxypolyethylene glycol (PEG)-modulated s-triazine-based multifunctional Schiff base/N,P-ligand L9 was prepared and used in Pd-catalyzed Heck-type carbonylative coupling reactions, affording diverse chalcone derivatives and 1,4-dicarbonyl esters in good yields.

20.
Cell Cycle ; 17(8): 963-973, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29712537

RESUMEN

It is believed that the alteration of tissue microenvironment would affect cancer initiation and progression. However, little is known in terms of the underlying molecular mechanisms that would affect the initiation and progression of breast cancer. In the present study, we use two murine mammary tumor models with different speeds of tumor initiation and progression for whole genome expression profiling to reveal the involved genes and signaling pathways. The pathways regulating PI3K-Akt signaling and Ras signaling were activated in Fvb mice and promoted tumor progression. Contrastingly, the pathways regulating apoptosis and cellular senescence were activated in Fvb.B6 mice and suppressed tumor progression. We identified distinct patterns of oncogenic pathways activation at different stages of breast cancer, and uncovered five oncogenic pathways that were activated in both human and mouse breast cancers. The genes and pathways discovered in our study would be useful information for other researchers and drug development.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Mamarias Animales/genética , Neoplasias Mamarias Animales/patología , Transducción de Señal/genética , Animales , Estudios de Cohortes , Matriz Extracelular/metabolismo , Femenino , Genotipo , Humanos , Ratones Endogámicos , Estadificación de Neoplasias , Análisis de Componente Principal , Reproducibilidad de los Resultados , Regulación hacia Arriba/genética
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