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Here we report the formation of a 3D NaCl-type binary porous superstructure via coassembly of two colloidal polyhedral metal-organic framework (MOF) particles having complementary sizes, shapes, and charges. We employed a polymeric-attenuated Coulombic self-assembly approach, which also facilitated the coassembly of these MOF particles with spherical polystyrene particles to form 2D binary superstructures. Our results pave the way for using MOFs to create sophisticated superstructures comprising particles of various sizes, shapes, porosities, and chemical compositions.
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Here, we report the synthesis of BCN-93, a meltable, functionalized, and permanently porous metal-organic polyhedron (MOP) and its subsequent transformation into amorphous or crystalline, shaped, self-standing, transparent porous films via melting and subsequent cooling. The synthesis entails the outer functionalization of a MOP with meltable polymer chains: in our model case, we functionalized a Rh(II)-based cuboctahedral MOP with poly(ethylene glycol). Finally, we demonstrate that once melted, BCN-93 can serve as a porous matrix into which other materials or molecules can be dispersed to form mixed-matrix composites. To illustrate this, we combined BCN-93 with one of various additives (either two MOF crystals, a porous cage, or a linear polymer) to generate a series of mixed-matrix films, each of which exhibited greater CO2 uptake relative to the parent film.
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The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [18F]AlF-ABI, a novel 18F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [18F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity (KD = 35.6 nM). Upon administration, [18F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through in vitro cell experiments and in vivo blocking PET imaging. These findings suggest that [18F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.
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Benzimidazóis , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Microambiente Tumoral , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/química , Benzimidazóis/química , Benzimidazóis/farmacologia , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , HumanosRESUMO
Self-assembly of colloidal particles into ordered superstructures enables the development of novel advanced materials for diverse applications such as photonics, electronics, sensing, energy conversion, energy storage, diagnosis, drug or gene delivery, and catalysis. Recently, polyhedral metal-organic framework (MOF) particles have been proposed as promising colloidal particles to form ordered superstructures, based on their colloidal stability, size-tunability, rich polyhedral shapes, porosity and multifunctionality. In this review, we present a comprehensive overview of strategies for the self-assembly of colloidal MOF particles into ordered superstructures of different dimensionalities, highlighting some of their properties and applications, and sharing thoughts on the self-assembly of MOF particles.
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Self-assembly of colloidal particles into ordered superstructures is an important strategy to discover new materials, such as catalysts, plasmonic sensing materials, storage systems, and photonic crystals (PhCs). Here we show that porous covalent organic frameworks (COFs) can be used as colloidal building particles to fabricate porous PhCs with an underlying face-centered cubic (fcc) arrangement. We demonstrate that the Bragg reflection of these can be tuned by controlling the size of the COF particles and that species can be adsorbed within the pores of the COF particles, which in turn alters the Bragg reflection. Given the vast number of existing COFs, with their rich properties and broad modularity, we expect that our discovery will enable the development of colloidal PhCs with unprecedented functionality.
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PURPOSE: Evans blue as an albumin binder has been widely used to improve pharmacokinetics and enhance tumor uptake of radioligands, including prostate-specific membrane antigen (PSMA) targeting agents. The goal of this study is to develop an optimal Evans blue-modified radiotherapeutic agent that could maximize the absolute tumor uptake and tumor absorbed dose thus the therapeutic efficacy to allow treatment of tumors even with moderate level of PSMA expression. METHODS: [177Lu]Lu-LNC1003 was synthesized based on PSMA-targeting agent and Evans blue. Binding affinity and PSMA targeting specificity were verified through cell uptake and competition binding assay in 22Rv1 tumor model that has moderate level of PSMA expression. SPECT/CT imaging and biodistribution studies in 22Rv1 tumor-bearing mice were performed to evaluate the preclinical pharmacokinetics. Radioligand therapy studies were conducted to systematically assess the therapeutic effect of [177Lu]Lu-LNC1003. RESULTS: LNC1003 showed high binding affinity (IC50 = 10.77 nM) to PSMA in vitro, which was comparable with that of PSMA-617 (IC50 = 27.49 nM) and EB-PSMA-617 (IC50 = 7.91 nM). SPECT imaging of [177Lu]Lu-LNC1003 demonstrated significantly improved tumor uptake and retention as compared with [177Lu]Lu-EB-PSMA and [177Lu]Lu-PSMA-617, making it suitable for prostate cancer therapy. Biodistribution studies further confirmed the remarkably higher tumor uptake of [177Lu]Lu-LNC1003 (138.87 ± 26.53%ID/g) over [177Lu]Lu-EB-PSMA-617 (29.89 ± 8.86%ID/g) and [177Lu]Lu-PSMA-617 (4.28 ± 0.25%ID/g) at 24 h post-injection. Targeted radioligand therapy results showed noteworthy inhibition of 22Rv1 tumor growth after administration of a single dose of 18.5 MBq [177Lu]Lu-LNC1003. There was no obvious antitumor effect after [177Lu]Lu-PSMA-617 treatment under the same condition. CONCLUSION: In this study, [177Lu]Lu-LNC1003 was successfully synthesized with high radiochemical purity and stability. High binding affinity and PSMA targeting specificity were identified in vitro and in vivo. With greatly enhanced tumor uptake and retention, [177Lu]Lu-LNC1003 has the potential to improve therapeutic efficacy using significantly lower dosages and less cycles of 177Lu that promises clinical translation to treat prostate cancer with various levels of PSMA expression.
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Glutamato Carboxipeptidase II , Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Distribuição Tecidual , Azul Evans/uso terapêutico , Glutamato Carboxipeptidase II/metabolismo , Antígenos de Superfície/metabolismo , Neoplasias da Próstata/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Linhagem Celular Tumoral , Lutécio/uso terapêutico , Lutécio/farmacocinéticaRESUMO
Benzamide (BZA), a small molecule that can freely cross cell membranes and bind to melanin, has served as an effective targeting group for melanoma theranostics. In this study, a novel pyridine-based BZA dimer (denoted as H-2) was labeled with 68Ga ([68Ga]Ga-H-2) for positron emission tomography (PET) imaging of malignant melanomas. [68Ga]Ga-H-2 was obtained with high radiochemical yield (98.0 ± 2.0%) and satisfactory radiochemical purity (>95.0%). The specificity and affinity of [68Ga]Ga-H-2 were confirmed in melanoma B16F10 cells and in vivo PET imaging of multiple tumor models (B16F10 tumors, A375 melanoma, and lung metastases). Monomeric [68Ga]Ga-H-1 was prepared as a control radiotracer to verify the effects of the molecular structure on pharmacokinetics. The values of the lipid-water partition coefficient of [68Ga]Ga-H-2 and [68Ga]Ga-H-1 demonstrated hydrophilicity with log P = -2.37 ± 0.07 and -2.02 ± 0.09, respectively. PET imaging and biodistribution showed a higher uptake of [68Ga]Ga-H-2 in B16F10 primary and metastatic melanomas than that in A375 melanomas. However, the relatively low uptake of monomeric [68Ga]Ga-H-1 in B16F10 tumors and high accumulation in nontarget organs resulted in poor PET imaging quality. This study demonstrates the synthesis and preclinical evaluation of the novel pyridine-based BZA dimer [68Ga]Ga-H-2 and indicates that the dimer tracer has promising applications in malignant melanoma-specific PET imaging because of its high uptake and long-time retention in malignant melanoma.
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Radioisótopos de Gálio , Melanoma Experimental , Animais , Radioisótopos de Gálio/química , Distribuição Tecidual , Melanoma Experimental/diagnóstico por imagem , Melanoma Experimental/metabolismo , Benzamidas/química , Tomografia por Emissão de Pósitrons/métodos , Piridinas , Linhagem Celular Tumoral , Melanoma Maligno CutâneoRESUMO
(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which have now become a severe public health problem worldwide. ß-Adrenergic receptor (ß-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous research has demonstrated that Bruton's tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-ß related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by ß-AR overactivation; (2) Methods: In vivo: Male C57BL/6J mice were treated with or without the ß-AR agonist isoproterenol (ISO) to establish a cardiac fibrosis animal model; (3) Results: In vivo: Results showed that the BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by ß-AR. In vitro: Results showed that ZB alleviated ß-AR-induced cardiac fibroblast activation and macrophage pro-inflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited ß-AR-induced cardiac fibrosis and inflammation by the BTK, STAT3, NF-κB, and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates ß-AR-induced cardiac fibrosis and inflammation.
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Cardiopatias , Fosfatidilinositol 3-Quinases , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Tirosina Quinase da AgamaglobulinemiaRESUMO
Erlotinib is a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Overcoming erlotinib resistance is crucial to improve the survival of advanced non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. It is also an important clinical problem that urgently needs a solution. In this study, we explored strategies to overcome erlotinib resistance from the perspective of energy metabolism. SIRT6 is a histone deacetylase. Here, we found that high expression of SIRT6 is associated with poor prognosis of lung adenocarcinoma, especially in EGFR-mutated NSCLC patients. The next cell experiment found that SIRT6 expression increased in erlotinib-resistant cells, and SIRT6 expression was negatively correlated with the sensitivity of NSCLC to erlotinib. Inhibition of SIRT6 promoted erlotinib-induced apoptosis in erlotinib-resistant cells, and glycolysis in drug-resistant cells was also inhibited. Functional studies have shown that SIRT6 increases glycolysis through the HIF-1α/HK2 signaling axis in drug-resistant cells and inhibits the sensitivity of NSCLC cells to erlotinib. In addition, the HIF-1α blocker PX478-2HCL attenuated the glycolysis and erlotinib resistance induced by SIRT6. More importantly, we confirmed the antitumor effect of SIRT6 inhibition combined with erlotinib in NSCLC-bearing mice. Our findings indicate that the cancer metabolic pathway regulated by SIRT6 may be a new target for attenuating NSCLC erlotinib resistance and has potential as a biomarker or therapeutic target to improve outcomes in NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sirtuínas , Animais , Camundongos , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Glicólise/genética , Histona Desacetilases/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Sirtuínas/genética , Sirtuínas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , HumanosRESUMO
PURPOSE: Stimulator of interferon genes (STING) protein plays a vital role in the immune surveillance of tumor microenvironment. Monitoring STING expression in tumors benefits the relevant STING therapy. This study aimed to develop a novel 18F-labeled agonist, dimeric amidobenzimidazole (diABZI), and firstly evaluate the feasibility of noninvasive positron emission tomography (PET) imaging of STING expression in the tumor microenvironment. METHODS: An analog of the STING agonist NOTA-DABI was synthesized and labeled with 18F via Al18F-NOTA complexation (denoted as [18F]F-DABI). Physicochemical properties, STING protein-binding affinity, and specificity of [18F]F-DABI were evaluated using cell uptake and docking assays. In vivo small-animal PET imaging and biodistribution studies of [18F]F-DABI in tumor-bearing mice were performed to verify the pharmacokinetics and tumor targeting ability. The correlation between tumor uptake and STING expression was also analyzed. RESULTS: [18F]F-DABI was produced conveniently with high radiochemical yield (44 ± 15%), radiochemical purity (> 97%) and molar activity (15-30 GBq/µmol). In vitro binding assays demonstrated that [18F]F-DABI has a favorable affinity and specificity for STING with a KD of 12.98 ± 2.07 nM. In vivo studies demonstrated the specificity of [18F]F-DABI for PET imaging of STING expression with B16F10 tumor uptake of 10.93 ± 0.93%ID/g, which was significantly different from that of blocking groups (3.13 ± 0.88%ID/g, ***p < 0.0001). Furthermore, tumor uptake of [18F]F-DABI was well positively correlated with STING expression in different tumor types. Biodistribution results demonstrated that [18F]F-DABI was predominately uptaken in the liver and intestines, indicating its hepatobiliary elimination. CONCLUSION: This proof-of-concept study demonstrated a STING-binding radioligand for PET imaging, which could be used as a potential companion diagnostic tool for related STING-agonist therapies.
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Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Animais , Camundongos , Radioisótopos de Flúor/farmacocinética , Distribuição Tecidual , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Expressão Gênica , InterferonsRESUMO
Fibroblast activation protein (FAP), a fundamental component of the tumor stroma, is overexpressed in cancer-associated fibroblasts (CAFs). As a promising theranostic probe, we evaluated whether the FAP inhibitor (FAPI) dimer (DOTA-2P[FAPI]2) is more effective than its monomeric analogs for FAP-targeted radionuclide therapy. [68Ga]Ga/[177Lu]Lu-DOTA-2P(FAPI)2 were assayed in a stability study, small-animal positron emission tomography (PET) and single-photon emission computed tomography (SPECT), biodistribution, and radionuclide therapy to comprehensively evaluate their preclinical pharmacokinetics. The pharmacokinetics of [68Ga]Ga-DOTA-2P(FAPI)2 and [177Lu]Lu-DOTA-2P(FAPI)2 were determined in FAP-positive hepatocellular carcinoma patient-derived xenografts (PDXs) and HT-1080-FAP cell-derived xenografts (CDXs). [68Ga]Ga-DOTA-2P(FAPI)2 and [177Lu]Lu-DOTA-2P(FAPI)2 were stable in phosphate-buffered saline for 4 h. The tumor retention of [68Ga]Ga-DOTA-2P(FAPI)2 was better than that of [68Ga]Ga-FAPI-46 in HT-1080-FAP CDXs, while healthy organs showed low tracer uptake and fast body clearance. In single-photon emission computed tomography, [177Lu]Lu-DOTA-2P(FAPI)2 showed a higher uptake and longer retention for tumors in both PDXs and CDXs from 1-48 h. [177Lu]Lu-DOTA-2P(FAPI)2 showed the best inhibition of tumor growth in PDXs and CDXs. DOTA-2P(FAPI)2 has increased tumor uptake and retention properties compared to FAPI-46, which significantly improves the use of FAPI-based vectors for PET imaging and radionuclide therapy. [177Lu]Lu-DOTA-2P(FAPI)2 may be safe and effective for the treatment of FAP-positive malignant tumors.
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Fibroblastos Associados a Câncer , Neoplasias , Animais , Radioisótopos de Gálio , Humanos , Proteínas de Membrana/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fosfatos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição TecidualRESUMO
OBJECTIVE: To investigate feasibility of the quantitative parameters of dual-energy computed tomography (DECT) to assess therapy response in advanced non-small cell lung cancer (NSCLC) compared with the traditional enhanced CT parameters based on the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. METHODS: Forty-five patients with unresectable locally advanced NSCLC who underwent DECT before and after chemotherapy or concurrent chemoradiotherapy (cCRT) were prospectively enrolled. By comparing baseline studies with follow-up, patients were divided into two groups according to RECIST guidelines as follows: disease control (DC, including partial response and stable disease) and progressive disease (PD). The diameter (D), attenuation, iodine concentration and normalized iodine concentration of arterial and venous phases (ICA, ICv, NICA, NICv) and the percentage of these changes pre- and post-therapy were measured and calculated. The Pearson correlation was used to analyze correlation between various quantitative parameters. The receiver operating characteristic (ROC) curves were used to evaluate accuracy of therapy response prediction. RESULTS: The change percentages of Attenuation (Δ-Attenuation-A and Δ-Attenuation-V), IC (ΔICA and ΔICV) and NIC (ΔNICA and ΔNICV) pre- and post-therapy correlate with the change percentage of D (ΔD). Among these, ΔICA strongly correlates with ΔD (râ=â0.793, Pâ<â0.001). The areas under ROC curves generated using Δ-Attenuation-A, ΔICA, and ΔNICA are 0.796, 0.900, and 0.880 with the corresponding cutoff value of 9.096, -15.692, and -4.7569, respectively, which are significantly different (Pâ<â0.001). CONCLUSIONS: The quantitative parameters of DECT iodine map, especially iodine concentration, in arterial phase provides a new quantitative image marker to predict therapy response of patients diagnosed with advanced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Iodo , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Meios de Contraste , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Tomografia Computadorizada por Raios X/métodosRESUMO
An efficient method for the construction of various pyrazolo[5,1-a]isoquinolines has been achieved via Ru(ii)-catalyzed α-carbonyl sulfoxonium ylide annulations with aryl substituted pyrazoles. This oxidant-free transformation occurred through pyrazole-directed C-H activation, Ru-carbene insertion, and acid-promoted carbonyl condensation processes, enabling dual C-C and C-N bond formation. A broad substrate scope with respect to both coupling components worked efficiently with high yields.
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BACKGROUND: Macroprolactin mostly composed of an immunoglobulin G (IgG) and a monomeric prolactin (PRL) represents the major circulating PRL form in the patients with macroprolactinemia that are usually asymptomatic and may not require treatment. In this study, we aimed to evaluate the prevalence of antithyroid and antinuclear antibodies, as well as the IgG subclass distributions in the patients suspected for macroprolactinemia. METHODS: From January to July in 2018, totally 317 patients with elevated PRL were subjected to the polyethylene glycol (PEG) precipitation assay. The patients with recovery rates of ≤60% were subjected for IgG subclass determination and autoantibody testing including thyroid peroxidase antibody (aTPO), antithyroglobulin antibody (aTG), and antinuclear antibodies (ANA). RESULTS: The higher the post-PEG PRL recovery rates, the less typical hyperprolactinemia symptoms and the higher prevalence of autoantibodies were observed. The IgG1 and IgG3 were the predominant subclasses in the PRL-IgG complexes according to the immunoprecipitation experiments. CONCLUSION: The patients with post-PEG PRL recovery rates of <40% and 40%-60% were likely to represent two distinct populations of different clinical presentations. The prevalence of autoantibodies and IgG subclasses distribution suggested their pathogenic significance in the development of macroprolactinemia.
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Autoanticorpos/sangue , Hiperprolactinemia , Imunoglobulina G , Adulto , China , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/epidemiologia , Hiperprolactinemia/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Polietilenoglicóis , Prolactina/imunologia , Adulto JovemRESUMO
Alkaline phosphatase (ALP) is an important enzyme that is associated with many human diseases, so the quantitative detection of ALP is vital from a clinical perspective. Nevertheless, most fluorescent assays for monitoring ALP depend on aggregation-induced quenching (ACQ), single-signal modulation, or a "signal off" mode, which suffer from poor sensitivity, a "false positive" problem, and low signal output. In this work, we utilized the electrostatically driven self-assembly of glutathione-capped gold nanoclusters (GSH-AuNCs, which show aggregation-induced emission, AIE) and amino-modified silicon nanoparticles (SiNPs) to create a hybrid probe (SiNPs@GSH-AuNCs). This nanohybrid probe showed emission from the SiNPs at around 470 nm as well as aggregation-induced emission enhancement (AIEE) of the GSH-AuNCs at 580 nm. The AIEE of the GSH-AuNCs was quenched in the presence of KMnO4, but the AIEE was recovered by adding ascorbic acid as an oxidation-reduction reaction occurred between KMnO4 and the ascorbic acid. The fluorescence of the SiNPs remained constant whether the AIEE was quenched or not, meaning that the fluorescence of the SiNPs could be used as an internal reference. In a typical enzymatic reaction, ascorbic acid 2-phosphate is hydrolyzed by ALP to produce ascorbic acid. Therefore, the hybrid probe was shown to allow the ratiometric detection of ALP, with a linear range of 0.5-10 U L-1 and a limit of detection (LOD) of 0.23 U L-1. Finally, the proposed analytical strategy was successfully applied to detect ALP in human serum samples and to determine the concentration of an ALP inhibitor. Graphical Abstract.
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Fosfatase Alcalina/sangue , Ouro/química , Fosfatase Alcalina/análise , Ácido Ascórbico/análise , Inibidores Enzimáticos/análise , Glutationa/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Padrões de Referência , Silício/química , Espectrometria de FluorescênciaRESUMO
This study was performed to investigate the prognostic significance of a cumulative score based on the preoperative plasma fibrinogen and serum albumin (FA score) in operable esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative fibrinogen, and albumin concentrations were retrospectively reviewed in patients who underwent transthoracic esophagectomy. The optimal cutoff value was defined as 4.0 g/L for fibrinogen according to previous studies and as 41.0 g/L for albumin for the lower quartile. Subjects with elevated fibrinogen and decreased albumin levels were allocated a score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the abnormalities were allocated a score of 0. The preoperative FA score was significantly associated with tumor length, depth of invasion, lymph node involvement, tumor-node-metastasis (TNM) stage, and the modified Glasgow Prognostic Score (mGPS). No significant differences in age, gender, tumor location, degree of differentiation, smoking or alcohol consumption were found between groups. Univariate survival analysis revealed that high preoperative FA score (1/2) was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.675; 95% confidence interval (CI), 1.278-2.195; P < 0.001] and overall survival (OS) (HR, 1.685; 95% CI, 1.268-2.239; P < 0.001). Furthermore, it remained an independent prognostic indicator for both DFS (HR, 1.394; 95% CI, 1.035-1.879; P = 0.029) and OS (HR, 1.369; 95% CI, 1.010-1.878; P = 0.048) in multivariable Cox regression analysis. A high preoperative FA score could significantly predict impaired long-term survival for ESCC patients who underwent transthoracic esophagectomy.
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Neoplasias Esofágicas/sangue , Carcinoma de Células Escamosas do Esôfago/sangue , Esofagectomia/mortalidade , Fibrinogênio/análise , Albumina Sérica/análise , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Adulto JovemRESUMO
The sesquiterpenoid curdione is one of the main bioactive components in the essential oil of Rhizoma Curcumae (Curcuma wenyujin, Curcuma phaeocaulis, and Curcuma kwangsiensis), which has been clinically used for the treatment of cancer in mainland China. Recently it was reported that natural curdione could be hydroxylated by Aspergillus niger and transferred to its corresponding curcumalactones under acidic conditions. Based on this study, the development of a sesquiterpenoid library through the "mirror-image" manipulation of bioactive (non)natural curdione scaffolds by chemical and biological approaches is presented herein. A. niger induced the hydroxylation of two pairs of curdione enantiomers, yielding the corresponding mirror-image hydroxylated curdiones. Simultaneously, the acid-mediated intramolecular "ene" rearrangements of these curdiones and hydroxylated curdione enantiomers yielded the corresponding mirror-image curcumalactones and hydroxylated curcumalactones. Among the 16 pairs of enantiomers obtained in this study, 23 compounds are new sesquiterpenoids. These curdione and curcumalactone derivatives are of particular interest, as they have the potential to be used as lead compounds and scaffolds in drug discovery.
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Curcuma/química , Óleos Voláteis/química , Sesquiterpenos de Germacrano/química , Aspergillus niger/metabolismo , China , Técnicas de Química Combinatória , Descoberta de Drogas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Rizoma/química , Sesquiterpenos , EstereoisomerismoRESUMO
BACKGROUND: This study was conducted to investigate the effect and mechanism of the nitrogen oxide 4-hydroxy- 2,2,6,6-tetramethylpiperidine (Tempol) on cerebral resuscitation caused by asphyxia-induced cardiac arrest. METHODS: Airway occlusion-induced asphyxia at the end of expiration was used to establish the rat cerebral ischaemia-hypoxia injury model. A total of 90 adult male Sprague-Dawley rats were randomly divided into the three groups. The Tempol and conventional cardiopulmonary resuscitation (CPR) groups were further divided into four subgroups according to different time points. RESULTS: After cerebral ischaemia, independent heart rate following asphyxia appeared earlier, and the success rate of primary recovery and the neurological function score of rats were higher in the Tempol group than in the conventional CPR group. The serum neuron-specific enolase (NSE) levels in the Tempol and conventional CPR groups were significantly higher within 6 to 48 h than that in the blank control group. The serum NSE level was significantly lower in the Tempol group than the conventional CPR group. CONCLUSIONS: After global cerebral ischaemia-hypoxia, the antioxidant Tempol improved cerebral resuscitation by reducing oxidative stress injuries and post-CPR cerebral damage. The NSE level can be used as an early detection index in the diagnosis of global cerebral ischaemia-hypoxia injuries. KEY WORDS: Cerebral ischemia; Neuron-specific enolase; Rats; Tempol.
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The stimulator of interferon genes (STING) is a vital protein to the immune surveillance of the tumor microenvironment. In this study, we develop novel inhibitor-based radioligands and evaluate their feasibility for noninvasive visualization of STING expression in tumor-bearing mice. Analogous compounds to STING inhibitors C170 and C176 were synthesized and labeled with 131I and 18F to attain [131I]I-NFIP and [18F]F-NFEP, respectively. The radiosynthesis was achieved with high radiochemical purity (>95%) and molar activity (28.56-48.89 GBq/µmol). The affinity and specificity of tracers were assessed through cell uptake and docking experiments, demonstrating that [131I]I-NFIP exhibited high specificity for STING, with a cell-based IC50 value of 7.56 nM. Small-animal PET/SPECT imaging and biodistribution studies in tumor-bearing mice models were performed to verify the tracers' pharmacokinetics and tumor-targeting capabilities (n = 3/group). SPECT imaging demonstrated that [131I]I-NFIP rapidly accumulated in the Panc02 tumor quickly at 30 min post-injection, with a tumor-to-muscle (T/M) ratio of 2.03 ± 0.30. This ratio significantly decreased in the blocking group (1.10 ± 0.14, **P < 0.01, n = 3). Furthermore, tumor uptake and the T/M ratio of [131I]I-NFIP were positively associated with STING expression. In summary, [131I]I-NFIP is the first STING-specific inhibitor-based radioligand offering the potential for visualizing STING status in tumors.
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In this paper, we successfully synthesize phosphoric acid functionalized graphene oxide (PGO) based on acid modification of graphene oxide. The composite membrane is further prepared by adding PGO into sulfonated poly(aryl ether ketone sulfone) containing carboxyl groups matrix (C-SPAEKS). The PGO as well as the composite membranes were characterized by a series of tests. The prepared composite proton exchange membranes (PEMs) have good mechanical and electrochemical properties. Compared to the C-SPAEKS membrane, the best composite membrane has a tensile strength of 40.7 MPa while exhibiting superior proton conductivity (110.17 mS cm-1 at 80 °C). In addition, the open-circuit voltage and power density of C-SPAEKS@1% PGO are 0.918 V and 792.17 mW cm-2, respectively. Compared with C-SPAEKS (0.867 V and 166 mW cm-2), it can be seen that our work has a certain effect on the improvement of the single cell performance. The above results demonstrate that the functionalized graphene oxide has greatly improved the electrochemical performance and even the overall performance of PEMs.