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1.
Ann Hematol ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38969929

RESUMO

Wilms tumor 1 (WT1) gene mutations are infrequent in myelodysplastic syndrome (MDS), but MDS with WT1 mutations (WT1mut) is considered high risk for acute myeloid leukemia (AML) transformation. The influence of WT1 mutations in patients with MDS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We performed a retrospective analysis of 136 MDS with excess blasts 2 (MDS-EB2) patients with available WT1 status who underwent their first allo-HSCT between 2017 and 2022 in our center. There were 20 (20/136, 15%) cases in the WT1mut group and 116 (116/136, 85%) cases in the WT1 wild-type (WT1wt) group. WT1mut patients had a higher 2-year cumulative incidence of relapse (CIR) than WT1wt cases (26.2% vs. 9.4%, p = 0.037) after allo-HSCT. Multivariate analysis of relapse showed that WT1 mutations (HR, 6.0; p = 0.002), TP53 mutations (HR, 4.2; p = 0.021), and ≥ 5% blasts in bone marrow (BM) at transplantation (HR, 6.6; p = 0.004) were independent risk factors for relapse. Patients were stratified into three groups according to the risk factors. Two-year CIR differed significantly in high-, intermediate-, and low-risk groups (31.8%, 11.6%, and 0%, respectively). Hence, WT1 mutations may be related to post-transplant relapse in patients with MDS-EB2, which warrants further study.

2.
Ann Hematol ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907755

RESUMO

Disease recurrence is the leading cause of treatment failure in patients with RUNX1::RUNXT1-positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant maintenance therapy, guided by monitoring minimal residual disease (MRD), is commonly administered; however, relapse rates remain high. This prospective study aimed to assess the effectiveness and safety of epigenetic agents as prophylactic therapy in patients with RUNX1::RUNXT1-positive AML. Thirty high-risk patients received prophylactic therapy (n = 17 and n = 13 in the chidamide and AZA groups, respectively) between January 2019 and July 2023. 34 high-risk patients who received preemptive treatment due to molecular relapse were included in the analysis. The two-year relapse-free survival (RFS) and overall survival (OS) were significantly higher in the prophylactic group compared to the preemptive group (82.82% vs. 51.38%, P = 0.014; 86.42% vs. 56.16%, P = 0.025, respectively); 2-year cumulative incidence of relapse rates were 13.8% and 36.40%, respectively (P = 0.037). In conclusion, prophylactic therapy with epigenetic agents may improve long-term prognosis and is well-tolerated in patients with RUNX1::RUNXT1-positive high-risk AML. Timely post-transplant prophylactic therapy may be more effective than preemptive therapy based on positive MRD results.

3.
Front Immunol ; 15: 1341255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464517

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) is an uncommon but highly aggressive hematological malignancy. It has high recurrence and mortality rates and is challenging to treat. This study conducted bioinformatics analyses, compared genetic expression profiles of healthy controls with patients having T-ALL/T-LBL, and verified the results through serological indicators. Data were acquired from the GSE48558 dataset from Gene Expression Omnibus (GEO). T-ALL patients and normal T cells-related differentially expressed genes (DEGs) were investigated using the online analysis tool GEO2R in GEO, identifying 78 upregulated and 130 downregulated genes. Gene Ontology (GO) and protein-protein interaction (PPI) network analyses of the top 10 DEGs showed enrichment in pathways linked to abnormal mitotic cell cycles, chromosomal instability, dysfunction of inflammatory mediators, and functional defects in T-cells, natural killer (NK) cells, and immune checkpoints. The DEGs were then validated by examining blood indices in samples obtained from patients, comparing the T-ALL/T-LBL group with the control group. Significant differences were observed in the levels of various blood components between T-ALL and T-LBL patients. These components include neutrophils, lymphocyte percentage, hemoglobin (HGB), total protein, globulin, erythropoietin (EPO) levels, thrombin time (TT), D-dimer (DD), and C-reactive protein (CRP). Additionally, there were significant differences in peripheral blood leukocyte count, absolute lymphocyte count, creatinine, cholesterol, low-density lipoprotein, folate, and thrombin times. The genes and pathways associated with T-LBL/T-ALL were identified, and peripheral blood HGB, EPO, TT, DD, and CRP were key molecular markers. This will assist the diagnosis of T-ALL/T-LBL, with applications for differential diagnosis, treatment, and prognosis.


Assuntos
Linfoma de Células T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mapas de Interação de Proteínas/genética , Transcriptoma , Biologia Computacional/métodos
4.
Exp Hematol Oncol ; 13(1): 16, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360825

RESUMO

The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and 224 (37.33%) patients in ELN-2022 favorable-, intermediate-, and adverse-risk group respectively and 86 patients (14.33%) experienced a shift in risk stratification compared to ELN-2017. Median and maximum follow-up time were 2.89 (95% CI 2.67 to 3.03) years and 8.78 years. The median overall survival (OS) was 73.8% (95% CI 67.5% to 80.3%), 63.9% (95% CI 56.7% to 72.0%) and 57.6% (95% CI 50.4% to 65.9%) in ELN-2022 favorable-, intermediate-, and adverse-risk group (P < 0.001). OS shortened significantly as the ELN-2022 risk stratification increased but didn't significantly in ELN-2017 intermediate-risk compared to favorable-risk. Both ELN-2022 and ELN-2017 adverse-risk were associated with increased cumulative incidence of relapse (CIR). Time-dependent receiver operating characteristic (ROC) analysis showed that both ELN-2017 and ELN-2022 risk systems had limited prognostic ability for OS. We modified ELN-2022 risk system with pre-transplant minimal residual disease (MRD) and the modified risk system performed a significantly superior efficacy to ELN-2022 system.

5.
Transfusion ; 64(2): 348-356, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38158888

RESUMO

BACKGROUND: The quality and quantity of hematopoietic stem cells in apheresis products are essential to the success of peripheral blood hematopoietic stem cell transplantation (PB-HSCT). While the flow cytometry measurement of CD34+ cells as a golden standard for stem cell count is labor and cost-intensive, hematopoietic progenitor cell number evaluated by XN Sysmex series automated hematology analyzers (XN-HPC) is suggested as a surrogate marker. MATERIALS AND METHODS: We evaluated the correlation and consistency of XN-HPC and CD34+ cell count in apheresis samples from both allogeneic donors and autologous patients during PB-HSCT. RESULTS: Good correlation and consistency were observed between XN-HPC and CD34+ cell counts in harvests collected from healthy donors (R = .852) rather than autologous patients (R = .375). Subgroup analysis showed that the correlation was especially poor when autologous patients used plerixafor as an additional mobilizer or were diagnosed with multiple myeloma (MM). In the setting of allogeneic transplantation, the correlation coefficients were even better in samples from non-first-round apheresis (R = .951), with high white blood cell (WBC) counts (R = .941), or having successful engraftment within 2 weeks (R = .895). ROC analysis suggested that an optimal XN-HPC count of 1127 × 106 /L best predicted a sufficient yield of CD34+ stem cells, with diagnostic sensitivity and specificity being 92% and 72%, respectively (AUC = 0.852). CONCLUSIONS: XN-HPC is a sufficient quantitative marker for stem cell assessment of harvest yield in allogeneic but not autologous HSCT.


Assuntos
Remoção de Componentes Sanguíneos , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Transplante de Células-Tronco de Sangue Periférico , Humanos , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/química , Antígenos CD34 , Contagem de Células
6.
Pharmacol Res ; 193: 106812, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37271425

RESUMO

Polyphenols, also known as phenolic compounds, are chemical substances containing aromatic rings as well as at least two hydroxyl groups. Natural phenolic compounds exist widely in plants, which protect plants from ultraviolet radiation and other insults. Phenolic compounds have superior pharmacological and nutritional properties (antimicrobial, antibacterial, antiviral, anti-sclerosis, antioxidant, and anti-inflammatory activities), which have been paid more and more attention by the scientific community. Phenols can protect key cellular components from reactive free radical damage, which is mainly due to their property to activate antioxidant enzymes and alleviate oxidative stress and inflammation. It can also inhibit or isolate reactive oxygen species and transfer electrons to free radicals, thereby avoiding cell damage. It has a regulatory role in glucose metabolism, which has a promising prospect in the prevention and intervention of diabetes. It also prevents cardiovascular disease by regulating blood pressure and blood lipids. Polyphenols can inhibit cell proliferation by affecting Erk1/2, CDK, and PI3K/Akt signaling pathways. Polyphenols can function as enhancers of intrinsic defense systems, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Simultaneously, they can modulate multiple proteins and transcription factors, making them promising candidates in the investigation of anti-cancer medications. This review focuses on multiple aspects of phenolic substances, including their natural origins, production process, disinfection activity, oxidative and anti-inflammatory functions, and the effects of different phenolic substances on tumors.


Assuntos
Antioxidantes , Neoplasias , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Raios Ultravioleta , Estresse Oxidativo , Fenóis/farmacologia , Fenóis/uso terapêutico , Neoplasias/tratamento farmacológico , Polifenóis/farmacologia , Radicais Livres/metabolismo , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química
7.
Nat Commun ; 14(1): 2207, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072407

RESUMO

Limited numbers of available hematopoietic stem cells (HSCs) limit the widespread use of HSC-based therapies. Expansion systems for functional heterogenous HSCs remain to be optimized. Here, we present a convenient strategy for human HSC expansion based on a biomimetic Microniche. After demonstrating the expansion of HSC from different sources, we find that our Microniche-based system expands the therapeutically attractive megakaryocyte-biased HSC. We demonstrate scalable HSC expansion by applying this strategy in a stirred bioreactor. Moreover, we identify that the functional human megakaryocyte-biased HSCs are enriched in the CD34+CD38-CD45RA-CD90+CD49f lowCD62L-CD133+ subpopulation. Specifically, the expansion of megakaryocyte-biased HSCs is supported by a biomimetic niche-like microenvironment, which generates a suitable cytokine milieu and supplies the appropriate physical scaffolding. Thus, beyond clarifying the existence and immuno-phenotype of human megakaryocyte-biased HSC, our study demonstrates a flexible human HSC expansion strategy that could help realize the strong clinical promise of HSC-based therapies.


Assuntos
Biomimética , Megacariócitos , Humanos , Células-Tronco Hematopoéticas , Antígenos CD34 , Antígenos Comuns de Leucócito
8.
Hematology ; 27(1): 1230-1236, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36373698

RESUMO

OBJECTIVES: Sysmex® XN series hematopoietic progenitor cell (XN-HPC) is a sensitive, fast, and economic analytical method for predicting the yields of peripheral blood stem cell enumeration and products, and does not require a sophisticated or expensive workflow. However, various studies have shown that the characteristics of its diagnostic performance were non-uniform. METHODS: We performed a systematic inquiry using PubMed, Embase, and Cochrane Library, to comprehensively search for studies published before November 21, 2021. The pooled specificity (SPE), sensitivity (SEN), negative likelihood ratio (NLR), positive likelihood ratio (PLR), diagnostic odds ratio (DOR) and receiver operating characteristic (ROC) curves were summarized to appraise the diagnostic merit of XN-HPC. A forest plot was used to research the sensitivities and specificities of XN-HPC performance. Subgroup analysis was performed to investigate heterogeneity where of importance. RESULTS: Our research included four studies that assessed the diagnostic performance of XN-HPC in hematopoietic progenitor cell collection. The pooled accuracy was 95.4% (95% CI, 94.3-96.3), SPE was 0.81 (95% CI, 0.71-0.88), SEN was 0.95 (95% CI, 0.75-0.99), NLR was 0.06 (95% CI, 0.01-0.37), PLR was 5.0 (95% CI, 3.0-8.5), DOR was 78 (95% CI, 9-707) and the summary of the area under the ROC was 0.90 (95% CI, 0.87-0.92). Forest plot of sensitivities and specificities from XN-HPC test accuracy studies indicated the existence of high heterogeneity. We deduced that the patients were the source of heterogeneity via subgroup analysis. CONCLUSIONS: XN-HPC is an excellent diagnostic marker for quantitative detection of peripheral blood hematopoietic progenitor cells.


Assuntos
Células-Tronco Hematopoéticas , Imunoterapia , Humanos , Biomarcadores , Curva ROC , Sensibilidade e Especificidade
9.
Nanomaterials (Basel) ; 12(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36234444

RESUMO

Herein we present a facile synthesis of the graphene oxide-decorated binary transition metal oxides of Bi2O3 and MnO2 nanocomposites (Bi2O3/MnO2/GO) and their applications in the voltammetric detection of lead ions (Pb2+) in water samples. The surface morphologies, crystal structures, electroactive surface area, and charge transferred resistance of the Bi2O3/MnO2/GO nanocomposites were investigated through the scanning electron microscopy (SEM), power X-ray diffraction (XRD), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) techniques, respectively. The Bi2O3/MnO2/GO nanocomposites were further decorated onto the surface of a glassy carbon electrode (GCE), and Pb2+ was quantitatively analyzed by using square-wave anodic stripping voltammetry (SWASV). We explored the effect of the analytical parameters, including deposition potential, deposition time, and solution pH, on the stripping peak current of Pb2+. The Bi2O3/MnO2/GO nanocomposites enlarged the electroactive surface area and reduced the charge transferred resistance by significant amounts. Moreover, the synergistic enhancement effect of MnO2, Bi2O3 and GO endowed Bi2O3/MnO2/GO/GCE with extraordinary electrocatalytic activity toward Pb2+ stripping. Under optimal conditions, the Bi2O3/MnO2/GO/GCE showed a broad linear detection range (0.01-10 µM) toward Pb2+ detection, with a low limit of detection (LOD, 2.0 nM). The proposed Bi2O3/MnO2/GO/GCE electrode achieved an accurate detection of Pb2+ in water with good recoveries (95.5-105%).

10.
Proc Math Phys Eng Sci ; 478(2259): 20210957, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35350816

RESUMO

In this paper, we present a theory of smooth stable manifold for the non-instantaneous impulsive differential equations on the Banach space or Hilbert space. Assume that the non-instantaneous linear impulsive evolution differential equation admits a uniform exponential dichotomy, we give the conditions of the existence of the global and local stable manifolds. Furthermore, C k -smoothness of the stable manifold is obtained, and the periodicity of the stable manifold is given. Finally, an application to nonlinear Duffing oscillators with non-instantaneous impulsive effects is given, to demonstrate the existence of stable manifold.

11.
IEEE Trans Cybern ; 52(7): 7049-7059, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33471773

RESUMO

In this article, a continuous-time complex-valued projection neural network (CCPNN) in a matrix state space is first proposed for a general complex-variable basis pursuit problem. The proposed CCPNN is proved to be stable in the sense of Lyapunov and to be globally convergent to the optimal solution under the condition that the sensing matrix is not row full rank. Furthermore, an improved discrete-time complex projection neural network (IDCPNN) is proposed by discretizing the CCPNN model. The proposed IDCPNN consists of a two-step stop strategy to reduce the calculational cost. The proposed IDCPNN is theoretically guaranteed to be global convergent to the optimal solution. Finally, the proposed IDCPNN is applied to the reconstruction of sparse signals based on compressed sensing. Computed results show that the proposed IDCPNN is superior to related complex-valued neural networks and conventional basis pursuit algorithms in terms of solution quality and computation time.


Assuntos
Algoritmos , Redes Neurais de Computação
12.
Ann Transl Med ; 9(18): 1452, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34734004

RESUMO

BACKGROUND: In recent years, B-cell dysfunction has been found to play an important role in the pathogenesis of primary nephrotic syndrome (PNS). B cells play a pathogenic role by secreting antibodies against their target antigens after transforming into plasma cells. Therefore, this study aimed to screen the autoantibodies that cause PNS and explore their pathogenic mechanisms. METHODS: Western blotting and mass spectrometry were employed to screen and identify autoantibodies against podocytes in children with PNS. Both in vivo and in vitro experiments were used to study the pathogenic mechanism of PNS. The results were confirmed in a large multicenter clinical study in children. RESULTS: Annexin A2 autoantibody was highly expressed in children with PNS with a pathological type of minimal change disease (MCD) or focal segmental glomerulosclerosis without genetic factors. The mouse model showed that anti-Annexin A2 antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A2 antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A2 at Tyr24 on podocytes by reducing its binding to PTP1B, which led to the cytoskeletal rearrangement and damage of podocytes, eventually causing proteinuria and PNS. CONCLUSIONS: Annexin A2 autoantibody may be responsible for some cases of PNS with MCD/FSGS in children.

13.
J Hematol Oncol ; 14(1): 149, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530888

RESUMO

CD19 chimeric antigen receptor (CAR)-T cells have been used to treat patients with refractory chronic lymphocytic leukemia (CLL). However, approximately 50% of patients do not respond to this therapy. To improve the clinical outcome of these patients, it is necessary to develop strategies with other optimal targets to enable secondary or combinational CAR-T cell therapy. By screening a panel of surface antigens, we found that CD32b (FcγRIIb) was homogeneously expressed at high site density on tumor cells from CLL patients. We then developed a second-generation CAR construct targeting CD32b, and T cells transduced with the CD32 CAR efficiently eliminated the CD32b+ Raji leukemic cell line in vitro and in a mouse xenograft model. Furthermore, CD32b CAR-T cells showed cytotoxicity against primary human CLL cells that were cultured in vitro or transplanted into immunodeficient mice. The efficacy of CD32b CAR T cells correlated with the CD32b density on CLL cells. CD32b is not significantly expressed by non-B hematopoietic cells. Our study thus identifies CD32b as a potential target of CAR-T cell therapy for CLL, although further modification of the CAR construct with a safety mechanism may be required to minimize off-target toxicity.


Assuntos
Imunoterapia Adotiva , Leucemia Linfocítica Crônica de Células B/terapia , Receptores de IgG/genética , Animais , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Imunoterapia Adotiva/métodos , Leucemia Linfocítica Crônica de Células B/genética , Camundongos
14.
J Pain Res ; 14: 1699-1706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140806

RESUMO

PURPOSE: In patients requiring percutaneous kyphoplasty (PKP) for painful cervical spine metastases (PCSMs), the surgical approach is of utmost importance. Anterolateral and transoral routes are generally used at present, whereas PKP as well as percutaneous pediculoplasty (PPP) via posterolateral transpedicular approach (PTPA) has yet to be pursued in the treatment of PCSMs. The study was designed to evaluate safety and efficacy of PKP procedures combined with PPP via PTPA as treatment of PCSMs. PATIENTS AND METHODS: The patients with PCSMs were enrolled and housed in a database. The pain intensity of enrolled patients was gauged by Visual Analog Scale (VAS), ranging from 0 (none) to 10 (extreme). After preprocedural imaging assessment, combined PKP/PPP via PTPA was performed under the guidance of CT and fluoroscopic monitoring. Postprocedural VAS scores, complications, cement dosage, and hospitalization were recorded in the database for analysis. All cases were followed up for 6 months. RESULTS: Adult enrollees (7 women, 4 men) with PCSMs successfully underwent PKP/PPP via PTPA between February 2019 and January 2020, injected with 3.7±0.7 mL (range, 2.5-4.8 mL) of cement on average. Other than a single instance of asymptomatic cement leakage into paravertebral soft tissues, no complications ensued. Significant analgesic effects observed 24 hours after procedures were sustained for up to 6 months in follow-up surveys. Postprocedural hospitalizations were as brief as 2.2±0.8 days. CONCLUSION: Combined PKP/PPP via PTPA is safe and effective as treatment of PCSMs, enabling quick pain relief and patient recovery.

16.
Eye (Lond) ; 35(5): 1508-1512, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32636496
17.
J Neural Eng ; 17(5): 051004, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33002886

RESUMO

Developing reliable and user-friendly electroencephalography (EEG) electrodes remains a challenge for emerging real-world EEG applications. Classic wet electrodes are the gold standard for recording EEG; however, they are difficult to implement and make users uncomfortable, thus severely restricting their widespread application in real-life scenarios. An alternative is dry electrodes, which do not require conductive gels or skin preparation. Despite their quick setup and improved user-friendliness, dry electrodes still have some inherent problems (invasive, relatively poor signal quality, or sensitivity to motion artifacts), which limit their practical utilization. In recent years, semi-dry electrodes, which require only a small amount of electrolyte fluid, have been successfully developed, combining the advantages of both wet and dry electrodes while addressing their respective drawbacks. Semi-dry electrodes can collect reliable EEG signals comparable to wet electrodes. Moreover, their setup is as fast and convenient similar to that of dry electrodes. Hence, semi-dry electrodes have shown tremendous application prospects for real-world EEG acquisition. Herein, we systematically summarize the development, evaluation methods, and practical design considerations of semi-dry electrodes. Some feasible suggestions and new ideas for the development of semi-dry electrodes have been presented. This review provides valuable technical support for the development of semi-dry electrodes toward emerging practical applications.


Assuntos
Artefatos , Eletroencefalografia , Condutividade Elétrica , Eletrodos
18.
Oncol Rep ; 44(2): 477-486, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32468056

RESUMO

Liver cancer is the second leading cause of cancer­related deaths. Traditional therapeutic strategies, such as chemotherapy, targeted therapy and interventional therapy, are inefficient and are accompanied by severe side effects for patients with advanced liver cancer. Therefore, it is crucial to develop a safer more effective drug to treat liver cancer. Veratramine, a known natural steroidal alkaloid derived from plants of the lily family, exerts anticancer activity in vitro. However, the underlying mechanism and whether it has an antitumor effect in vivo remain unknown. In the present study, the data revealed that veratramine significantly inhibited HepG2 cell proliferation, migration and invasion in vitro. Moreover, it was revealed that veratramine induced autophagy­mediated apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway, which partly explained the underlying mechanism behind its antitumor activity. Notably, the results of in vivo experiments also revealed that veratramine treatment (2 mg/kg, 3 times a week for 4 weeks) significantly inhibited subcutaneous tumor growth of liver cancer cells, with a low systemic toxicity. Collectively, the results of the present study indicated that veratramine efficiently suppressed liver cancer HepG2 cell growth in vitro and in vivo by blocking the PI3K/Akt/mTOR signaling pathway to induce autophagic cell death. Veratramine could be a potential therapeutic agent for the treatment of liver cancer.


Assuntos
Morte Celular Autofágica , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Alcaloides de Veratrum/administração & dosagem , Animais , Movimento Celular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Alcaloides de Veratrum/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Mater Sci Eng C Mater Biol Appl ; 109: 110615, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228941

RESUMO

Four nanostructured MnO2 with various controllable morphologies, including nanowires, nanorods, nanotubes and nanoflowers were synthesized, and then further composited with nitrogen-doped graphene (NG) with the assistance of ultrasonication. The surface morphologies, phase structures, and electrochemical performances of the proposed MnO2/NG nanohybrids were investigated by various techniques, and their catalytic activities on the electrooxidation of dopamine (DA) and uric acid (UA) were compared systematically. The sensing performances were found to be highly correlated with their morphologies. Among these morphologies, the nanoflower-like MnO2, composited with NG, displayed the most sensitive response signals for DA and UA. The boosted electrocatalytic activity was ascribed to the unique porous structure, large electroactive area, and low charge transfer resistance (Rct), which facilitated the electron transfer between electrode and analytes. Two linear response ranges (0.1 µM-10 µM and 10 µM-100 µM) were accompanied with very low detection limits of 34 nM and 39 nM for DA and UA, respectively. Moreover, the successful application of the MnO2NFs/NG composites for the simultaneous detection of DA and UA in human serum was realized using second-derivative linear sweep voltammetry (SDLSV). These findings give valuable insights for understanding the morphology-dependent sensing properties of MnO2 based nanomaterials, which is conducive to the rapid development of ubiquitous MnO2-based electrochemical sensors.


Assuntos
Dopamina/sangue , Técnicas Eletroquímicas , Grafite/química , Compostos de Manganês/química , Nitrogênio/química , Óxidos/química , Ácido Úrico/sangue , Humanos
20.
Nanomaterials (Basel) ; 10(2)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054018

RESUMO

Titania/electro-reduced graphene oxide nanohybrids (TiO2/ErGO) were synthesized by the hydrolysis of titanium sulfate in graphene oxide suspension and in situ electrochemical reduction. It provides a facile and efficient method to obtain nanohybrids with TiO2 nanoparticles (TiO2 NPs) uniformly coated by graphene nanoflakes. TiO2/ErGO nanohybrids were characterized by transmission electron microscopy, X-ray diffraction, cyclic voltammogram, and electrochemical impedance spectroscopy in detail. Compared with pure ErGO and TiO2 NPs, TiO2/ErGO nanohybrids greatly enhanced the electrocatalytic activity and voltammetric response of Allura Red. In the concentration range of 0.5-5.0 µM, the anodic peak currents of Allura Red were linearly correlated to their concentrations. However, the linear relationship was changed to the semi-logarithmic relationship at a higher concentration region (5.0-800 µM). The detection limit (LOD) was 0.05 µM at a signal-to-noise ratio of 3. The superior sensing performances of the proposed sensor can be ascribed to the synergistic effect between TiO2 NPs and ErGO, which provides a favorable microenvironment for the electrochemical oxidation of Allura Red. The proposed TiO2/ErGO/GCE showed good reproducibility and stability both in determination and in storage, and it can accurately detect the concentration of Allura Red in milk drinks, providing an efficient platform for the sensitive determination of Allura Red with high reliability, simplicity, and rapidness.

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