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1.
Anal Chem ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146222

RESUMO

A water-induced electron-deficient dye, the supramolecule perylene diimide (PDI), has been identified recently. PDI possesses advantages such as easy reduction, nontoxicity, low cost, and simple preparation, making it a promising candidate for electrochemiluminescence (ECL) sensing platforms. In this study, a series of PDI supramolecular systems with morphological changes were prepared by utilizing water molecules to induce PDI self-assembly. This method improves the π-π stacking interactions between PDI molecules and effectively mitigates the aggregation-caused quenching (ACQ) effect on the luminous efficiency of the coplanar polycyclic aromatic hydrocarbon PDI. It is noteworthy that excellent ECL emission performance of the PDI supramolecular system was observed at -0.4 V. This low excitation potential aids in preserving antigen-antibody bioactivity and ensures accurate identification of the immune response. As a proof of concept, a dual-mode immunosensing platform for carcinoembryonic antigen (CEA) detection was constructed using an enzymatic biocatalytic precipitation (EBCP) strategy. The dual-mode immunosensor exhibited good detection performance in the concentration range of 0.001-80 ng·mL-1, presenting an advanced bioprotective analytical method for CEA detection.

2.
Small ; 20(26): e2310476, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38282388

RESUMO

In recent years, carbon nitride (CN) has attracted substantial attention in the field of electrochemiluminescence (ECL) applications, owing to its outstanding optical and electronic properties. However, the passivation of CN during the ECL process has contributed to reduced stability and poor repeatability. While some studies have tried to boost ECL performance by altering CN through doping and vacancies, effectively suppressing CN passivation at high potentials continues to be challenge. In this study, the built-in electric field and the Schottky barrier effect is used to expedite the transfer of electrons from CN to the molybdenum disulfide (MoS2) conduction band. This transfer deterred excessive electron injection into the CN band, thus mitigating its electrochemical degradation. Moreover, by introducing nickel nanoparticles (Ni NPs) as catalytic active sites, it is facilitated that the decomposition of potassium persulfate (K2S2O8), thereby enhancing both the stability and intensity of ECL emission. In the end, the application of ternary heterostructure as sensing platform for the cancer biomarker carcinoembryonic antigen (CEA) demonstrated high sensitivity. This research introduces a novel approach to overcome CN passivation, paving the way for more promising applications of CN in energy, environmental, and biosensing fields.

3.
J Transl Med ; 22(1): 96, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263194

RESUMO

BACKGROUND: Periodontitis is a chronic oral inflammatory disease that seriously affects people's quality of life. The purpose of our study was to investigate the correlation between the systemic immune inflammation index (SII) and periodontitis by utilizing a large national survey. This will establish a reference for the early identification and management of periodontitis. METHODS: This study comprised the adult US population who participated in a national periodontitis surveillance project during the six years from 2009 to 2014. Through the utilization of univariate and multivariate weighted logistic regression, we investigated the correlation between the systemic immune inflammation index and periodontitis. Additionally, we employed sensitivity analyses to evaluate the robustness of our findings. RESULTS: The study involved 10,366 participants with an average age of 51.00 years, of whom 49.45% were male (N = 5126) and 50.55% were female (N = 5240). The prevalence of periodontitis is estimated to be about 38.43% in the US adults aged 30 or older population. Our logistic regression models indicated a positive association between a SII higher than 978 × 109/L and periodontitis. The elder group (aged 50 or older) with SII higher than 978 × 109/L demonstrated a significant correlation with periodontitis in the fully adjusted model (Odds Ratio [OR] = 1.409, 95% Confidence Interval [CI] 1.037, 1.915, P = 0.022). However, there is no statistical difference among adults aged 30 to 50. The robustness of our findings was confirmed through sensitivity analyses. CONCLUSIONS: Our study highlights that SII is associated with periodontitis in a nationally representative sample of US adults. And the SII is significantly associated with a high risk of periodontitis in individuals aged 50 or older.


Assuntos
Periodontite , Qualidade de Vida , Adulto , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Inflamação , Modelos Logísticos
4.
Cell Commun Signal ; 22(1): 378, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39061097

RESUMO

Artesunate (ART), a natural product isolated from traditional Chinese plant Artemisia annua, has not been extensively explored for its anti-melanoma properties. In our study, we found that ART inhibited melanoma cell proliferation and induced melanoma cell ferroptosis. Mechanistic study revealed that ART directly targets Ido1, thereby suppressing Hic1-mediated transcription suppression of Hmox1, resulting in melanoma cell ferroptosis. In CD8+ T cells, ART does not cause cell ferroptosis due to the low expression of Hmox1. It also targets Ido1, elevating tryptophan levels, which inhibits NFATc1-mediated PD1 transcription, consequently activating CD8+ T cells. Our study uncovered a potent and synergistic anti-melanoma efficacy arising from ART-induced melanoma cell ferroptosis and concurrently enhancing CD8+ T cell-mediated immune response both in vivo and in vitro through directly targeting Ido1. Our study provides a novel mechanistic basis for the utilization of ART as an Ido1 inhibitor and application in clinical melanoma treatment.


Assuntos
Artesunato , Ferroptose , Indolamina-Pirrol 2,3,-Dioxigenase , Melanoma , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Ferroptose/efeitos dos fármacos , Animais , Artesunato/farmacologia , Artesunato/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Linhagem Celular Tumoral , Humanos , Camundongos Endogâmicos C57BL , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética
5.
Anal Chem ; 95(44): 16225-16233, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37877873

RESUMO

Compared with the accuracy of a single signal and the limitation of environmental applicability, the application value of dual-mode detection is gradually increasing. To this end, based on the photothermal effect of Ag/Co embedded N-rich mesoporous carbon nanomaterials (AgCo@NC NPs), we designed a dual-mode signal response system for the detection of α-fetoprotein (AFP). First, AgCo@NC NPs act as a photothermal immunoprobe that converts light energy into heat driven by a near-infrared (NIR) laser and obtains temperature changes corresponding to the analyte concentration on a hand-held thermal imager. In addition, this temperature recognition system can significantly improve the efficiency of Fenton-like reactions. AgCo@NC NPs act as peroxidase mimics to initiate the generation of poly N-isopropylacrylamide (PNIPAM, resistance enhancer) by cascade catalysis and the degradation of methylene blue (MB), thus enabling electrochemical testing. The dual-mode assay ranges from 0.01 to 100 and 0.001-10 ng/mL, with lower limits of detection (LOD) of 3.2 and 0.089 pg/mL, respectively, and combines visualization, portability, and high efficiency, opening new avenues for future clinical diagnostics and inhibitor studies.


Assuntos
Nanoestruturas , alfa-Fetoproteínas , Luz
6.
Anal Chem ; 95(33): 12459-12469, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37566460

RESUMO

To sensitively monitor trace amounts of alternariol (AOH) in fruits, a dual-mode aptamer sensor utilizing the dual-function nanomaterial PoPD/Ru-Au was developed. This sensor provides both electrochemical (EC) and electrochemiluminescence (ECL) signals, which can greatly avoid the potential false positive of the traditional single signal, thus enhancing the accuracy and reliability of detection results. Polyo-phenylenediamine (PoPD), known for its favorable EC response, can also assist in enhancing the ECL behavior of Ru-Au. Furthermore, Ru-Au demonstrates excellent ECL performance and effectively activates K2S2O8 to amplify the EC response of PoPD. The complementary effect of the two can effectively amplify the final detection signal. Additionally, the PoPD/Ru-Au nanomaterial exhibits excellent electrical conductivity, further enhancing the EC and ECL response signals. The experimental results demonstrate that the EC detection range of AOH was 0.01-100 ng/mL, while the ECL detection range was 0.001-100 ng/mL, both exhibiting a satisfactory linear relationship. Therefore, the mutual verification of the detection results can be highly realized, and the purpose of avoiding wrong detection can be achieved.

7.
Anal Chem ; 95(18): 7109-7117, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37098252

RESUMO

In this paper, a novel donor-acceptor pair was creatively proposed based on the principle of electrochemiluminescence resonance energy transfer (ECL-RET): luminol immobilized on polyethyleneimine (PEI)-functionalized manganese-based single-atom nanozymes (Mn SANE/PEI-luminol, donor) and a PtCu-grafted hollow metal polydopamine framework (PtCu/h-MPF, acceptor). A quenched ECL immunosensor was constructed for the ultrasensitive analysis of carcinoembryonic antigen (CEA). Mn SANE, as an efficient novel coreaction accelerator with the outstanding performance of significantly activating H2O2 to produce large amounts of ROS, was further modified by the coreactant PEI, which efficiently immobilized luminol to form a self-enhanced emitter. As a result, the electron transport distance was effectively shortened, the energy loss was reduced, and luminol achieved a high ECL efficiency. More importantly, PtCu-grafted h-MPF (PtCu/h-MPF) was proposed as a novel quencher. The UV-vis spectra of PtCu/h-MPF partially overlap with the ECL spectra of Mn SANE/PEI-luminol, which can effectively trigger the ECL-RET behavior between the donor and the acceptor. The multiple quenching effect on Mn SANE/PEI-luminol was achieved, which significantly improved the sensitivity of the immunosensor. The prepared immunosensor exhibited good linearity in the concentration range of 10-5 to 80 ng/mL. The results indicate that this work provides a new method for the early detection of CEA in clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Luminol , Antígeno Carcinoembrionário/análise , Polietilenoimina , Técnicas Biossensoriais/métodos , Peróxido de Hidrogênio , Técnicas Eletroquímicas/métodos , Medições Luminescentes/métodos , Imunoensaio/métodos , Limite de Detecção
8.
Acta Pharmacol Sin ; 43(6): 1419-1429, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34593973

RESUMO

The multi-generation heredity trait of hypertension in human has been reported, but the molecular mechanisms underlying multi-generational inheritance of hypertension remain obscure. Recent evidence shows that prenatal inflammatory exposure (PIE) results in increased incidence of cardiovascular diseases, including hypertension. In this study we investigated whether and how PIE contributed to multi-generational inheritance of hypertension in rats. PIE was induced in pregnant rats by intraperitoneal injection of LPS or Poly (I:C) either once on gestational day 10.5 (transient stimulation, T) or three times on gestational day 8.5, 10.5, and 12.5 (persistent stimulation, P). Male offspring was chosen to study the paternal inheritance. We showed that PIE, irrespectively induced by LPS or Poly (I:C) stimulation during pregnancy, resulted in multi-generational inheritance of significantly increased blood pressure in rat descendants, and that prenatal LPS exposure led to vascular remodeling and vasoconstrictor dysfunction in both thoracic aorta and superior mesenteric artery of adult F2 offspring. Furthermore, we revealed that PIE resulted in global alteration of DNA methylome in thoracic aorta of F2 offspring. Specifically, PIE led to the DNA hypomethylation of G beta gamma (Gßγ) signaling genes in both the F1 sperm and the F2 thoracic aorta, and activation of PI3K/Akt signaling was implicated in the pathologic changes and dysregulated vascular tone of aortic tissue in F2 LPS-P offspring. Our data demonstrate that PIE reprogrammed DNA methylome of cells from the germline/mature gametes contributes to the development of hypertension in F2 PIE offspring. This study broadens the current knowledge regarding the multi-generation effect of the cumulative early life environmental factors on the development of hypertension.


Assuntos
Hereditariedade , Hipertensão , Efeitos Tardios da Exposição Pré-Natal , Animais , Epigenoma , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/genética , Inflamação/induzido quimicamente , Inflamação/genética , Lipopolissacarídeos/toxicidade , Masculino , Fosfatidilinositol 3-Quinases/genética , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Ratos
9.
J Nanobiotechnology ; 20(1): 300, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35752856

RESUMO

Deep tumor cells (cells in the center of solid tumors) play a crucial role in drug tolerance, metastasis, recurrence and microenvironment immune suppression. However, their deep location endows them with an untouched abdomen and makes them refractory to current treatments. Herein, we exploited the characteristic of higher autophagy in deep tumor cells than in superficial tumor cells and designed autophagy-responsive multifunctional nanoparticles (PGN) to enhance drug accumulation in deep tumor cells. PGNs were prepared by densely coating poly (lactic-co-glycolic acid) (PLGA) with cationic autophagy-responsive cell-penetrating peptide (GR9) and anionic 2,3-dimethylmaleic anhydride (DMA)-modified DSPE-PEG. The suitable nanoparticle size (122.4 nm) and charge-neutral surface (0.21 mV) of the NPs enabled long blood circulation. The hydrolysis of surface-anchored anionic DMA in the acidic microenvironment led to the exposure of the GR9 peptide and enhance tumor penetration. Once the PGN arrived in deep tumor cells with strong autophagy, GR9 was cut off by an autophagy shear enzyme, and the nanoparticles remained in the cells to undergo degradation. Furthermore, we prepared docetaxel (DTX) and chloroquine (CQ) loaded d-PGN. CQ inhibits autophagosome fusion with lysosomes, resulting in autophagosome accumulation, which further enhances the sensitivity of d-PGN to autophagy and their deep tumor retention. In vivo experiments showed that drug-loaded d-PGN achieved excellent antitumor efficacy with a peak inhibition rate of 82.1%. In conclusion, autophagy-responsive multifunctional nanoparticles provide a novel potential strategy for solid tumor treatment.


Assuntos
Nanopartículas , Neoplasias , Autofagia , Linhagem Celular Tumoral , Cloroquina/farmacologia , Docetaxel/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Microambiente Tumoral
10.
Mikrochim Acta ; 189(9): 334, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35970980

RESUMO

To accomplish ultra-sensitive detection of alpha-fetoprotein(AFP), a novel electrochemical immunosensor using polydopamine-coated Fe3O4 nanoparticles (PDA@Fe3O4 NPs) as a smart label and polyaniline (PANI) and Au NPs as substrate materials has been created. The sensor has the following advantages over typical immunoassay technology: (1) The pH reaction causes PDA@Fe3O4 NPs to release Prussian blue (PB) prosoma while also destroying the secondary antibody label and immunological platform and lowering electrode impedance; (2) PB has a highly efficient catalytic effect on H2O2, allowing for the obvious amplification of electrical impulses; (3) PANI was electrodeposited on the electrode surface to avoid PB loss and signal leakage, which effectively absorbed and fixed PB while considerably increasing electron transmission efficiency. The sensor's detection limit was 0.254 pg·mL-1 (S/N = 3), with a detection range of 1 pg·mL-1 to 100 ng·mL-1. The sensor has a high level of selectivity, repeatability, and stability, and it is predicted to be utilized to detect AFP in real-world samples.


Assuntos
Técnicas Biossensoriais , alfa-Fetoproteínas , Preparações de Ação Retardada , Técnicas Eletroquímicas , Compostos Férricos/química , Ouro , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Imunoensaio , Indóis/análise , Indóis/química , Polímeros/química
11.
J Cell Mol Med ; 24(1): 618-631, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31724308

RESUMO

Proliferation and metastasis are significantly malignant characteristics of human lung cancer, but the underlying molecular mechanisms are poorly understood. Chromobox 4 (CBX4), a member of the Polycomb group (PcG) family of epigenetic regulatory factors, enhances cellular proliferation and promotes cancer cell migration. However, the effect of CBX4 in the progression of lung cancer is not fully understood. We found that CBX4 is highly expressed in lung tumours compared with adjacent normal tissues. Overexpression of CBX4 significantly promotes cell proliferation and migration in human lung cancer cell lines. The knockdown of CBX4 obviously suppresses the cell growth and migration of human lung cancer cells in vitro. Also, the proliferation and metastasis in vivo are blocked by CBX4 knockdown. Furthermore, CBX4 knockdown effectively arrests cell cycle at the G0/G1 phase through suppressing the expression of CDK2 and Cyclin E and decreases the formation of filopodia through suppressing MMP2, MMP9 and CXCR4. Additionally, CBX4 promotes proliferation and metastasis via regulating the expression of BMI-1 which is a significant regulator of proliferation and migration in lung cancer cells. Taken together, these data suggest that CBX4 is not only a novel prognostic marker but also may be a potential therapeutic target in lung cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Ligases/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , Complexo Repressor Polycomb 1/metabolismo , Proteínas do Grupo Polycomb/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Feminino , Humanos , Ligases/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Complexo Repressor Polycomb 1/genética , Proteínas do Grupo Polycomb/genética , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Acta Pharmacol Sin ; 41(11): 1416-1426, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32973325

RESUMO

Immunotherapies for cancers may cause severe and life-threatening cardiotoxicities. The underlying mechanisms are complex and largely elusive. Currently, there are several ongoing clinical trials based on the use of activated invariant natural killer T (iNKT) cells. The potential cardiotoxicity commonly associated with this particular immunotherapy has yet been carefully evaluated. The present study aims to determine the effect of activated iNKT cells on normal and ß-adrenergic agonist (isoproterenol, ISO)-stimulated hearts. Mice were treated with iNKT stimulants, α-galactosylceramide (αGC) or its analog OCH, respectively, to determine their effect on ISO-induced cardiac injury. We showed that administration of αGC (activating both T helper type 1 (Th1)- and T helper type 2 (Th2)-liked iNKT cells) significantly accelerated the progressive cardiac injury, leading to enhanced cardiac hypertrophy and cardiac fibrosis with prominent increases in collagen deposition and TGF-ß1, IL-6, and alpha smooth muscle actin expression. In contrast to αGC, OCH (mainly activating Th2-liked iNKT cells) significantly attenuated the progression of cardiac injury and cardiac inflammation induced by repeated infusion of ISO. Flow cytometry analysis revealed that αGC promoted inflammatory macrophage infiltration in the heart, while OCH was able to restrain the infiltration. In vitro coculture of αGC- or OCH-pretreated primary peritoneal macrophages with primary cardiac fibroblasts confirmed the profibrotic effect of αGC and the antifibrotic effect of OCH. Our results demonstrate that activating both Th1- and Th2-liked iNKT cells is cardiotoxic, while activating Th2-liked iNKT cells is likely cardiac protective, which has implied key differences among subpopulations of iNKT cells in their response to cardiac pathological stimulation.


Assuntos
Cardiomegalia/etiologia , Cardiotônicos/uso terapêutico , Galactosilceramidas/efeitos adversos , Glicolipídeos/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Células T Matadoras Naturais/efeitos dos fármacos , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/patologia , Citocinas/metabolismo , Fibrose , Inflamação/prevenção & controle , Isoproterenol , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/classificação
13.
J Cell Mol Med ; 22(9): 4474-4485, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29993201

RESUMO

IR-783 is a kind of heptamethine cyanine dye that exhibits imaging, cancer targeting and anticancer properties. A previous study reported that its imaging and targeting properties were related to mitochondria. However, the molecular mechanism behind the anticancer activity of IR-783 has not been well demonstrated. In this study, we showed that IR-783 inhibits cell viability and induces mitochondrial apoptosis in human breast cancer cells. Exposure of MDA-MB-231 cells to IR-783 resulted in the loss of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) depletion, mitochondrial permeability transition pore (mPTP) opening and cytochrome c (Cyto C) release. Furthermore, we found that IR-783 induced dynamin-related protein 1 (Drp1) translocation from the cytosol to the mitochondria, increased the expression of mitochondrial fission proteins mitochondrial fission factor (MFF) and fission-1 (Fis1), and decreased the expression of mitochondrial fusion proteins mitofusin1 (Mfn1) and optic atrophy 1 (OPA1). Moreover, knockdown of Drp1 markedly blocked IR-783-mediated mitochondrial fission, loss of MMP, ATP depletion, mPTP opening and apoptosis. Our in vivo study confirmed that IR-783 markedly inhibited tumour growth and induced apoptosis in an MDA-MB-231 xenograft model in association with the mitochondrial translocation of Drp1. Taken together, these findings suggest that IR-783 induces apoptosis in human breast cancer cells by increasing Drp1-mediated mitochondrial fission. Our study uncovered the molecular mechanism of the anti-breast cancer effects of IR-783 and provided novel perspectives for the application of IR-783 in the treatment of breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carbocianinas/farmacologia , GTP Fosfo-Hidrolases/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Associadas aos Microtúbulos/genética , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/genética , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/genética , Citocromos c/metabolismo , Dinaminas , Feminino , GTP Fosfo-Hidrolases/antagonistas & inibidores , GTP Fosfo-Hidrolases/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Front Pharmacol ; 15: 1243353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482051

RESUMO

Introduction: Gypenoside is a natural extract of Gynostemma pentaphyllum (Thunb.) Makino, a plant in the Cucurbitaceae family. It has been reported to have antitumor effects on the proliferation, migration and apoptosis of various types of cancer cells. However, the use of gypenoside in the treatment of gastric cancer has not been studied. In the present study, we explored the therapeutic effect of gypenoside on gastric cancer and the potential molecular mechanism. Methods and Results: Our results showed that gypenoside induced apoptosis in HGC-27 and SGC-7901 cells in a time-dependent and dose-dependent manner. Network pharmacology analyses predicted that gypenoside exerts its therapeutic effects through the PI3K/AKT/mTOR signaling pathway. Furthermore, molecular docking and western blot experiments confirmed that gypenoside induced the apoptosis of gastric cancer cells through the PI3K/AKT/mTOR signaling pathway. In addition, network pharmacological analysis revealed that the common targets of gypenoside in gastric cancer were enriched in the immune effector process, PD-L1 expression, the PD-1 checkpoint pathway, and the Jak-STAT signaling pathway. Furthermore, molecular docking and western blot assays demonstrated that gypenoside could bind to STAT3 and reduce its phosphorylation. Thus, the transcription of PD-L1 was inhibited in gastric cancer cells. Moreover, coculture experiments of gastric cancer cells with gypenoside and primary mouse CD8+ T cells showed that gastric cancer cells treated with gypenoside could enhance the antitumor ability of T cells. Animal experiments confirmed the antitumor effect of gypenoside, and the expression of PD-L1 was significantly downregulated in the gypenoside-treated group. Conclusion: Gypenoside induced the apoptosis of gastric cancer cells by inhibiting the PI3K/AKT/mTOR pathway and simultaneously inhibited the expression of PD-L1 in gastric cancer cells, thus enhancing the antitumor immunity of T cells. This study provides a theoretical basis for applying gypenoside as a new therapeutic agent to enhance the efficacy of immunotherapy in gastric cancer.

17.
Bioelectrochemistry ; 159: 108729, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38772096

RESUMO

This study explores the principles of resonance energy transfer and adsorption modulation using composites of Cu2S-MPA/NGODs. These composites can efficiently control the quenching process of electrochemiluminescence (ECL). Mercaptopropionic acid (MPA) was added during the synthesis of Cu2S-MPA to enhance its attachment to nitrogen-doped graphene quantum dots (NGODs). The UV absorption peaks of NGODs coincided with the emission peaks of luminol ECL, enabling resonance energy transfer and enhancing the quenching capability of Cu2S-MPA. Meanwhile, there is another quenching strategy. When the readily reducible Cu+ ions underwent partial reduction to Cu when they were bound to NGODs. This weakened the electrocatalytic effect on reactive oxygen species (ROS) and had a detrimental impact on electron transfer. Under optimal conditions, the immunosensor ECL intensity decreased linearly with the logarithm of carcinoembryonic antigen (CEA) concentration in the range of 0.00001-40 ng/mL, with a detection limit of 0.269 fg/mL. The sensor was effectively utilized for the identification of CEA in actual serum samples.


Assuntos
Antígeno Carcinoembrionário , Cobre , Técnicas Eletroquímicas , Grafite , Medições Luminescentes , Pontos Quânticos , Cobre/química , Pontos Quânticos/química , Grafite/química , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/análise , Medições Luminescentes/métodos , Adsorção , Técnicas Eletroquímicas/métodos , Limite de Detecção , Ácido 3-Mercaptopropiônico/química , Humanos , Transferência de Energia , Técnicas Biossensoriais/métodos , Sulfetos
18.
J Adv Res ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38897272

RESUMO

INTRODUCTION: Chemoimmunotherapy, which benefits from the combination of chemotherapy and immunotherapy, has emerged as a promising strategy in cancer treatment. However, effectively inducing a robust immune response remains challenging due to the limited responsiveness across patients. Endoplasmic reticulum (ER) stress is essential for activating intracellular signaling pathways associated with immunogenic cell death (ICD), targeting drugs to ER might enhance ER stress and improve ICD-related immunotherapy. OBJECTIVES: To improve the immune response of Chemoimmunotherapy. METHODS: ER targeting nanoparticles TSE-CEL/NP were constructed to enhance immunogenic cancer cell death. Flow cytometry, confocal microscope, TEM and immunofluorescence were used to evaluate the ER targeting effect and immunogenic tumor cell death in vitro on B16F10 tumor cells. Unilateral and bilateral tumor models were constructed to investigate the efficacy of anti-tumor and immunotherapy in vivo. Lung metastasis B16F10 melanoma tumor-bearing mice were used to assess the anti-metastasis efficacy. RESULTS: TSE-CEL/NP could specially accumulate in ER, thereby induce ER stress. High ER stress trigger the exposure of CRT, the extracellular release of HMGB1 and ATP. These danger signals subsequently promote the recruitment and maturation of dendritic cells (DCs), which in turn increase the proliferation of cytotoxic T lymphocytes (CD8+ T cells), ultimately resulted in an improved immunotherapy efficacy against melanoma. Invivo experiments showed that TSE-CEL/NP exhibits excellent antitumor efficacy and triggers a strong immune response. CONCLUSION: Our findings demonstrated that celastrol ER targeting delivery could amplify immunogenic cell death in melanoma, which provide experimental basis for melanoma immunotherapy.

19.
Bioelectrochemistry ; 156: 108626, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38128442

RESUMO

By combining two different materials, metal-organic frameworks (MOF) and ß-cyclodextrins (ß-CD), a signal amplification electrochemical luminescence (ECL) immunosensor was constructed to realize the sensitive detection of AFP. The indium-based metal-organic framework (In-MOF) was used as the carrier of Ru(bpy)32+, and Ru(bpy)32+ was immobilized by In-MOF through suitable pore size and electrostatic interaction. At the same time, using host-guest recognition, ß-CD enriched TPA into the hydrophobic cavity for accelerating the electronic excitation of TPA, then, achieving the purpose of signal amplification. The signal amplification immunosensor structure is constructed among the primary antibody Ab1 connected to the Ru(bpy)32+@In-MOF modified electrode, AFP, BSA and the secondary antibody (Ab2) loaded with TPA-ß-CD. The immunosensor has a good linearity in the range of 10-5 ng/mL-50 ng/mL, and the low limit of detection (LOD) is 1.1 × 10-6 ng/mL. In addition, the electrochemiluminescence immunosensor that we designed has strong stability, good selectivity and repeatability, which provides a choice for the analysis of AFP.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , beta-Ciclodextrinas , Nanopartículas Metálicas/química , alfa-Fetoproteínas , Medições Luminescentes , Imunoensaio , Limite de Detecção , Estruturas Metalorgânicas/química , Técnicas Eletroquímicas
20.
Biosens Bioelectron ; 252: 116151, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38402725

RESUMO

Perylene diimide (PDI) is a readily reducible electron-deficient dye that exhibits strong photoluminescent properties, providing new opportunities for synthesizing novel electrochemiluminescence (ECL) emitters. In this study, ethylene glycol (EG) was used to induce the self-assembly of PDI supramolecules for the preparation of ultrathin EG-PDI nanosheets characterized by low crystallinity and weak stacking interaction. Notably, EG-PDI integrates luminescent and catalytic functions into one device, accelerating the interfacial electron transfer and the faster charge transfer kinetics of EG-PDI with K2S2O8. Furthermore, the narrow band gap of EG-PDI facilitates its excitation at an ultra-low potential (-0.3 V). To improve the efficiency of tumor marker analysis, multifunctional Au nanostars (ANS) was introduced both as an energy acceptor of the ECL system and a probe for the photothermal system. Dual-mode immunoassay have demonstrated superior analytical performance in detecting alpha-fetoprotein (AFP), meeting the requirements of modern clinical diagnostics in resource-limited environments.


Assuntos
Técnicas Biossensoriais , Imidas , Perileno/análogos & derivados , Imunoensaio , Etilenoglicóis
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