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1.
Eur J Neurosci ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764192

RESUMO

Alzheimer's disease (AD) stands as the prevalent progressive neurodegenerative disease, precipitating cognitive impairment and even memory loss. Amyloid biomarkers have been extensively used in the diagnosis of AD. However, amyloid proteins offer limited information about the disease process and accurate diagnosis depends on the presence of a substantial accumulation of amyloid deposition which significantly impedes the early screening of AD. In this study, we have combined plasma proteomics with an ensemble learning model (CatBoost) to develop a cost-effective and non-invasive diagnostic method for AD. A longitudinal panel has been identified that can serve as reliable biomarkers across the entire progression of AD. Simultaneously, we have developed a neural network algorithm that utilizes plasma proteins to detect stages of Alzheimer's disease. Based on the developed longitudinal panel, the CatBoost model achieved an area under the operating curve of at least 0.90 in distinguishing mild cognitive impairment from cognitively normal. The neural network model was utilized for the detection of three stages of AD, and the results demonstrated that the neural network model exhibited an accuracy as high as 0.83, surpassing that of the traditional machine learning model.

2.
Bioconjug Chem ; 32(8): 1763-1772, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34260853

RESUMO

Targeted radionuclide therapy (TRT) provides new and safe opportunities for cancer treatment and management with high precision and efficiency. Here we have designed a novel semiconducting polymer nanoparticle (SPN)-based radiopharmaceutical (211At-MeATE-SPN-GIP) for TRT against glucose-dependent insulinotropic polypeptide receptor (GIPR)-positive cancers to further explore the applications of nanoengineered TRT. 211At-MeATE-SPN-GIP was engineered via nanoprecipitation, followed by its functionalization with a glucose-dependent insulinotropic polypeptide (GIP) to target GIPR and deliver 211At for α therapy. The therapeutic effect and biological safety of 211At-MeATE-SPN-GIP were investigated using GIPR-overexpressing human pancreatic cancer CFPAC-1 cells and CFPAC-1-bearing mice. In this work, 211At-MeATE-SPN-GIP was produced with a radiochemical yield of 43% and radiochemical purity of 98%, which exhibited a specifically high uptake in CFPAC-1 cells, inducing cell cycle arrest at the G2/M phase and extensive DNA damage. In the CFPAC-1-bearing tumor model, 211At-MeATE-SPN-GIP exhibited high therapeutic efficiency, with no obvious side effects. The GIPR-specific binding of 211At-MeATE-SPN-GIP combined with effective inhibition of tumor growth and fewer side effects compared to control suggests that 211At-MeATE-SPN-GIP TRT holds great potential as a novel nanoengineered TRT strategy for patients with GIPR-positive cancer.


Assuntos
Astato/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Polímeros/química , Receptores dos Hormônios Gastrointestinais/metabolismo , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias Experimentais , Ligação Proteica , Radioisótopos , Receptores dos Hormônios Gastrointestinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Nanobiotechnology ; 19(1): 337, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689758

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastatingly malignant tumor with a high mortality. However, current strategies to treat PDAC generally have low efficacy and high side-effects, therefore, effective treatment against PDAC remains an urgent need. RESULTS: We report a semiconducting polymer nano-radiopharmaceutical with intrinsic photothermal capability and labeling with therapeutic radioisotope 177Lu (177Lu-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. 177Lu-SPN-GIP endowed good stability at physiological conditions, high cell uptake, and long retention time in tumor site. By virtue of combined radiotherapy (RT) and photothermal therapy (PTT), 177Lu-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, 177Lu-SPN-GIP could suppress the growth of the tumor stem cells and reverse epithelial mesenchymal transition (EMT), which may greatly reduce the occurrence of metastasis. CONCLUSION: Such strategy we developed could improve therapeutic outcomes over traditional RT as it is able to ablate tumor with relatively lower doses of radiopharmaceuticals to reduce its side effects.


Assuntos
Neoplasias Pancreáticas/metabolismo , Fototerapia/métodos , Pontos Quânticos , Compostos Radiofarmacêuticos , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Polímeros/química , Polímeros/farmacologia , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacologia , Nanomedicina Teranóstica , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Molecules ; 25(8)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316530

RESUMO

TiO2 nanotube arrays (TNAs) with tube lengths of 4, 6, and 7 µm were prepared via two-step anodization. Thereafter, ultraviolet (UV) photodetectors (PDs) with Au/TiO2/Au structures were prepared using these TNAs with different tube lengths. The effects of TNA length and device area on the performance of the device were investigated using in situ Raman spectroscopy. The maximum laser/dark current ratio was achieved by using a TNA with a size of 1 × 1 cm2 and a length of 7 µm, under a 532 nm laser. In addition, when the device was irradiated with a higher energy laser (325 nm), the UV Raman spectrum was found to be more sensitive than the visible Raman spectrum. At 325 nm, the laser/dark current ratio was nearly 24 times higher than that under a 532 nm laser. Six phonon modes of anatase TNAs were observed, at 144, 199, 395, 514, and 635 cm-1, which were assigned to the Eg(1), Eg(2), B1g(1), A1g/B1g(2), and Eg(3) modes, respectively. The strong low-frequency band at 144 cm-1 was caused by the O-Ti-O bending vibration and is a characteristic band of anatase. The results show that the performance of TNA-based PDs is length-dependent. Surface-enhanced Raman scattering signals of 4-mercaptobenzoic acid (4-MBA) molecules were also observed on the TNA surface. This result indicates that the length-dependent performance may be derived from an increase in the specific surface area of the TNA. In addition, the strong absorption of UV light by the TNAs caused a blueshift of the Eg(1) mode.


Assuntos
Nanotubos , Espectrofotometria , Análise Espectral Raman , Titânio , Raios Ultravioleta , Nanotubos/química , Nanotubos/ultraestrutura , Titânio/química , Difração de Raios X
5.
Tumour Biol ; 35(11): 11461-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25123262

RESUMO

The objective of this study is to identify the expression status and clinical implications of lipase member H (LIPH) in breast cancer in order to develop strategies for breast cancer management. LIPH expression status was detected in 346 breast cancer specimens by immunohistochemistry. The relationship between LIPH expression, clinico-pathological parameters, and prognosis of breast cancer was determined. LIPH expression was higher in breast cancer specimens than in paracarcinoma tissues (P=0.01). In total, 64.74% (224/346) of breast cancer samples had high expression of the LIPH protein. LIPH was related to tumor size, histological grade, lymph node metastasis, and distant metastasis (P=0.073, 0.001, 0.001, and 0.001, respectively). Furthermore, individuals with high LIPH expression had a significantly higher rate of distant metastasis and poorer disease-specific survival than those with no or low LIPH expression (P=0.01). A Cox regression test indicated that the LIPH protein was an independent prognostic factor (P=0.001). LIPH was differentially expressed in breast cancer individuals and is an independent prognostic factor for breast cancer as well as a potential target for its management.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Lipase/metabolismo , Adulto , Idoso , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
6.
HLA ; 103(3): e15442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488733

RESUMO

HLA-A*11:463 has one nucleotide change from HLA-A*11:01:01:01 at nucleotide 508 changing Lysine (146) to Glutamine.


Assuntos
Antígenos HLA-A , Nucleotídeos , Humanos , Masculino , Sequência de Bases , Alelos , Antígenos HLA-A/genética , China , Pai , Análise de Sequência de DNA
7.
ACS Nano ; 18(12): 9114-9127, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38477305

RESUMO

Immune checkpoint blockade (ICB) therapy is promising to revolutionize cancer regimens, but the low response rate and the lack of a suitable patient stratification method have impeded universal profit to cancer patients. Noninvasive positron emission tomography (PET) imaging in the whole body, upon coupling with specific biomarkers closely related to the immune response, could provide spatiotemporal information to prescribe cancer therapy. Herein, we demonstrate that antisilencing function 1a (ASF1a) could serve as a biomarker target to delineate tumor immune microenvironments by immune PET (iPET). The iPET radiotracer (68Ga-AP1) is designed to target ASF1a in tumors and predict immune response, and the signal intensity predicts anti-PD-1 (αPD-1) therapy response in a negative correlation manner. The ICB-resistant tumors with a high level of ASF1a as revealed by iPET (ASF1aHigh-iPET) are prescribed to be treated by either the combined 177Lu-labeled AP1 and αPD-1 or the standalone α particle-emitting 225Ac-labeled AP1, both achieving enhanced therapeutic efficacy and prolonged survival time. Our study not only replenishes the iPET arsenal for immune-related response evaluation by designing a reliable biomarker and a facile radiotracer but also provides optional therapeutic strategies for ICB-resistant tumors with versatile radionuclide-labeled AP1 peptides, which is promising for real-time clinical diagnosis and individualized therapy planning simultaneously.


Assuntos
Neoplasias , Radioisótopos , Humanos , Tomografia por Emissão de Pósitrons/métodos , Biomarcadores , Peptídeos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(3): 714-7, 2013 Mar.
Artigo em Zh | MEDLINE | ID: mdl-23705439

RESUMO

In the present article, three kinds of metal-organic coordination compounds were synthesized between 1,2-trans-(4-pyridyl)ethene (dpe) and sulfate of Cu(II), Zn(II) and Cd(I) by hydrothermal reactions. Infrared, Raman and ultraviolet-visible spectra of dpe and its metal--organic complexes were studied. Assignments of the main FTIR and Raman bands were done in detail. The relationship between these characteristic bands and the structure of ligands and coordination compounds was discussed. In the FTIR spectra, the co-vibration absorption band of C-C and C-N for dpe shifts to the higher wavenumbers for three metal-organic coordination compounds, respectively. In the Raman spectra, the corresponding vibration bands of C-N, C=C, C-C and C-H were also observed to shift to higher wavenumbers. In the UV-visible absorption spectra, Zn-dpe and Cd-dpe has an absorption peak which could be attributed to the ligand absorption itself. However, two absorption peaks were observed for the complex of Cu-dpe, which were ascribed to the ligand absorption band and d-d electronic transition in the coordination compound. This indicates that there is a great change in the absorption spectra for the same ligand but with different metal ions.

9.
Transpl Immunol ; 81: 101920, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37648035

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely applied for the treatment of hematologic malignancies, but autologous hematopoietic recovery (AR) after allo-HSCT is rare clinically, especially after myeloablative conditioning (MAC). The mechanism of AR remains unclear so far, but the prognosis for most patients is relatively good. Second transplantation is preferred after disease relapse. Starting from a real-life clinical case scenario, herein we reviewed some of the crucial issues of AR in light of recent refinements, and discussed our patients based on the current evidence.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Homólogo , Estudos Retrospectivos , Neoplasias Hematológicas/terapia , Prognóstico , Condicionamento Pré-Transplante , Doença Enxerto-Hospedeiro/patologia
10.
HLA ; 102(1): 89-90, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36951755

RESUMO

HLA-C*01:02:86 has one synonymous nucleotide C > T change from HLA-C*01:02:01:01 at nucleotide 879 (residue 269 Proline).


Assuntos
População do Leste Asiático , Antígenos HLA-C , Humanos , Sequência de Bases , Antígenos HLA-C/genética , Alelos , Análise de Sequência de DNA , Nucleotídeos
11.
ACS Nano ; 17(23): 23998-24011, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37988029

RESUMO

Programmed death-ligand 1 (PD-L1) is a specialized shield on tumor cells that evades the immune system. Even inhibited by PD-L1 antibodies, a cycling process constantly transports PD-L1 from inside to outside of cells, facilitating the renewal and replenishment of PD-L1 on the cancer cell membrane. Herein, we develop a sodium alginate hydrogel consisting of elesclomol-Cu and galactose to induce persistent cuproptosis, leading to the reduction of PD-L1 for radio-immunotherapy of colon tumors. First, a prefabricated hydrogel is synthesized by immobilizing elesclomol onto a sodium alginate saccharide chain through the coordination with bivalent copper ions (Cu2+), followed by incorporation of galactose. After implantation into the tumors, this prefabricated hydrogel can be further cross-linked in the presence of physiological calcium ions (Ca2+), resulting in the formation of a hydrogel with controlled release of elesclomol-Cu2+ (ES-Cu) and galactose. The hydrogel effectively induces the oligomerization of DLAT and cuproptosis in colorectal cancer cells. Interestingly, radiation-induced PD-L1 upregulation is abrogated in the presence of the hydrogel, releasing ES-Cu and galactose. Consequently, the sensitization of tumor to radiotherapy and immunotherapy is significantly improved, further prolonging the survival of tumor-bearing mice in both local and metastatic tumors. Our study introduces an approach that combines cuproptosis with immunotherapy and radiotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias do Colo , Animais , Camundongos , Cobre , Hidrogéis , Galactose , Ligantes , Neoplasias do Colo/tratamento farmacológico , Imunoterapia/métodos , Alginatos , Íons , Microambiente Tumoral
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(6): 1588-91, 2012 Jun.
Artigo em Zh | MEDLINE | ID: mdl-22870645

RESUMO

In the present article, two kinds of metal-organic coordination compounds were synthesized between 4-mercaptopyridine (4-MPy) and nitrate of Ag(I) and Cd(II) by a general solution reaction and evaporation. 4-mercaptopyridine and two transition metal complexes were investigated by means of infrared, Raman and ultraviolet-visible spectroscopic techniques, respectively. Assignments of the main FTIR and Raman bands were carried out in detail. The relationship between those characteristic bands and the structure of ligands and coordination compounds was discussed. In the FTIR spectra, the co-vibration absorption band of nu(C==C) and nu(C==N), for 4-MPy at 1 459 cm(-1) blue-shifted to 1 464 cm(-1) for both the metal-organic coordination compounds, respectively. The Raman spectra, for the two coordination compounds, at 1 004 and 1 008 cm(-1), which can be assigned to ring breathing vibration, at 1 617 and 1 615 cm ', which can be assigned to ring flex vibration, and at 720 and 720 cm(-1), which can be assigned to the composite vibration of beta(C--C) and nu(C--S) are similar, respectively.

13.
HLA ; 100(3): 275-277, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35524576

RESUMO

HLA-C*01:212 differs from HLA-C*01:02:01:01 by two non-synonmous nucleotide changes at positions 368 and 379 in exon 3.


Assuntos
Povo Asiático , Antígenos HLA-C , Alelos , China , Éxons/genética , Antígenos HLA-C/genética , Humanos , Análise de Sequência de DNA
14.
HLA ; 100(3): 265-266, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35524579

RESUMO

HLA-B*13:157 has one nucleotide change from HLA-B*13:02:01:01 at nucleotide 323 changing Tyrosine to Phenylalanine at residue 84.


Assuntos
Antígenos HLA-B , Nucleotídeos , Alelos , Sequência de Bases , Antígenos HLA-B/genética , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA
15.
HLA ; 100(3): 283-284, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35524580

RESUMO

HLA-C*15:244 has one nucleotide change from HLA-C*15:05:01:01 at nucleotide 308 changing Arginine to Glutamine at residue 79.


Assuntos
Genes MHC Classe I , Antígenos HLA-C , Alelos , Sequência de Bases , Antígenos HLA-C/genética , Humanos , Nucleotídeos , Análise de Sequência de DNA
16.
HLA ; 100(3): 268-270, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35524588

RESUMO

HLA-B*35:251:02 has one nucleotide change from HLA-B*35:22:01:01 at nucleotide 363 changing Serine to Arginine at residue 97.


Assuntos
Genes MHC Classe I , Antígenos HLA-B , Alelos , Sequência de Bases , Antígenos HLA-B/genética , Teste de Histocompatibilidade , Humanos , Nucleotídeos , Análise de Sequência de DNA
17.
HLA ; 100(3): 258-260, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35484782

RESUMO

HLA-A*11:398 has one nonsynonymous nucleotide change from HLA-A*11:01:01:01 at nucleotide 709, changing Isoleucine 213 to Valine.


Assuntos
Antígenos HLA-A , Nucleotídeos , Alelos , Sequência de Bases , China , Antígenos HLA-A/genética , Humanos , Análise de Sequência de DNA
18.
HLA ; 100(3): 270-271, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35478491

RESUMO

HLA-B*40:482 has one nucleotide change from HLA-B*40:06:01:01 at nucleotide 430 changing glycine to arginine at residue 120.


Assuntos
Antígenos HLA-B , Nucleotídeos , Alelos , Sequência de Bases , Antígenos HLA-B/genética , Humanos , Análise de Sequência de DNA
19.
HLA ; 100(2): 142-143, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35384353

RESUMO

One nucleotide replacement at position 728 of HLA-A*02:07:01 results in a novel allele, HLA-A*02:981.


Assuntos
Antígenos HLA-A , Alelos , Antígenos HLA-A/genética , Humanos , Análise de Sequência de DNA
20.
HLA ; 100(2): 151-153, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35384358

RESUMO

HLA-A*24:516 has one nucleotide change from HLA-A*24:02:01:01 at nucleotide 194 where Alanine (41) is changed to Glycine.


Assuntos
Antígenos HLA-A , Núcleo Familiar , Alelos , Sequência de Bases , China , Éxons/genética , Antígenos HLA-A/genética , Humanos , Nucleotídeos , Análise de Sequência de DNA
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