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Background: Ki-67 and human epidermal growth factor receptor 2 (HER2) are key biomarkers in evaluating the prognosis of colorectal adenocarcinoma (CRAC). The purpose of this study was to investigate the value of quantitative parameters in dual-layer spectral detector computed tomography (SDCT) for evaluating the expression of Ki-67 and HER2 in CRAC. Methods: In this retrospective, cross-sectional study, 88 eligible patients with pathologically confirmed CRAC were selected from Taicang Hospital of Traditional Chinese Medicine between May 2021 and April 2023. The study participants underwent enhanced SDCT of the whole abdomen within 2 weeks before to surgery, did not receive antitumor therapy, and had complete immunohistochemical (IHC) indexes. Patients with nonadenocarcinoma pathologic types, poor quality of spectral CT images, or no complete immunohistochemistry results were excluded. Spectral parameters including CT values at 40 and 100 keV, effective atomic number, iodine concentration (IC), the slope of the spectral Hounsfield unit (HU) curve (λHU), and normalized iodine concentration (NIC) in the arterial phase (AP) and venous phase (VP) were analyzed for their value in distinguishing between the high and low expression of Ki-67 and HER2-positive and -negative status in CRAC. The statistical significance of the SDCT parameters between the different groups of Ki-67 expression and those of HER2 status was assessed with the Mann-Whitney test. Spearman correlation analysis was used to analyze the correlation between the SDCT parameters and the extent of Ki-67 expression and HER2 expression status. The receiver operating characteristic (ROC) curve was used, and the area under the curve (AUC) was calculated. Results: The SDCT parameters of CT values at 40 keV, effective atomic number, IC, and the λHU in the VP showed significant differences between the Ki-67 high- and low-expression groups in CRAC (P=0.035, P=0.041, P=0.036, and P=0.044, respectively), with AUCs of 0.639 [95% confidence interval (CI): 0.512-0.766], 0.634 (95% CI: 0.508-0.761), 0.638 (95% CI: 0.510-0.766), and 0.633 (95% CI: 0.504-0.762), respectively. The expression of CRAC Ki-67 was positively correlated with CT values at 40 keV (r=0.227; P=0.034), effective atomic number (r=0.219; P=0.040), IC (r=0.225; P=0.035), and the λHU in VP (r=0.216; P=0.043). SDCT parameter values showed no statistical difference between negative and positive expression in HER2 (all P values >0.05). There was no significant correlation between SDCT parameters and the expression of HER2 in CRAC (all P values >0.05). Conclusions: The quantitative parameters of SDCT in the VP provide valuable information for distinguishing between the low expression and high expression of Ki-67 in CRAC.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease with a global prevalence of approximately 0.46%, causing significant impairments in patients' quality of life and an economic burden. Saussurea involucrata (SI) has long been used in traditional medicine to treat RA, but its underlying mechanism remains unclear. This study utilized network pharmacology and molecular docking to explore the potential pharmacological effects of bioactive compounds in SI on RA. A total of 27 active compounds were identified, along with 665 corresponding targets. Additionally, 593 disease-related targets were obtained from multiple databases, with 119 common targets shared with SI. The high-ranking targets mainly belong to the MAPK family and NF-κB pathway, including MAPK14, MAPK1, RELA, TNF, and MAPK8, all of which are associated with inflammation and joint destruction in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed significant pathways related to IL-17 signaling, Th17 cell differentiation, and osteoclast differentiation. Molecular docking and dynamic simulations demonstrated strong interactions between several flavonoids and RA-related targets. Xuelianlactone, Involucratin, and Flazin exhibit outstanding binding efficacy with targets such as MAPK1, MAPK8, and TNF. These findings provide valuable insights into the therapeutic potential of SI for RA and offer directions for further drug development.
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Artrite Reumatoide , Medicamentos de Ervas Chinesas , Saussurea , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Qualidade de Vida , Artrite Reumatoide/tratamento farmacológicoRESUMO
Many approaches have been employed to relieve hypoxia in solid tumors to enhance sensitivity to radiotherapy (RT), including O2 delivery or hydrogen peroxide (H2O2) decomposition strategies. To date, however, these modalities have been restricted by poor O2 loading, rapid O2 leakage, and limited endogenous H2O2 levels. To overcome these limitations, we therefore sought to develop an effective approach for the oxygen-independent treatment of hypoxic tumors. In this study, we designed a novel black phosphorus quantum dot (BPQD)/Escherichia coli (E. coli) hybrid system (BE) capable of facilitating the photothermal therapy (PTT) of hypoxic tumors. A simple electrostatic adsorption approach was used to conjugate BPQDs to E. coli. BE is capable of reliably targeting hypoxic tumors and mediating PTT. BPQDs in BE can directly facilitate X-ray-mediated radiosensitization of tumors, thereby achieving significant RT efficacy in response to lower doses of radiation, effectively and specifically damaging hypoxic tumor tissues to suppress the growth of tumors. Our results highlight this BE system as a novel approach to tumor radiosensitization with great potential for clinical application.
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Neoplasias , Pontos Quânticos , Humanos , Terapia Fototérmica , Fósforo , Peróxido de Hidrogênio , Escherichia coli , Neoplasias/terapia , Hipóxia/terapia , Linhagem Celular TumoralRESUMO
OBJECTIVE: To investigate the distribution of helicobacter pylori-related genotypes of oipA, babA2, and babB in patients with gastrointestinal diseases. Methods: The retrospective study was conducted at the Jiamusi College, Heilongjiang University of Traditional Chinese Medicine, Harbin, China, and comprised data from February 2017 to May 2020 of patients of either gender 20-80 years who underwent gastroscopy. An instrument based on polymerase chain reaction was used to amplify oipA, babA2 and babB genes, and their distribution in terms of gender, age and pathological types was analysed. RESULTS: Among the 116 patients, 52(44.8%) had oipA genotype, 48(41.2%) babA2, and 72 (62.1%) babB, respectively, and the size of amplified products of 486bp, 219bp and 362bp, respectively. The infection rate of oipA and babB genotypes was highest [26(50.0%) and 31(43.1%)]in those aged 61-80 years, and lowest [9(17.3%) and 15(20.8%)]in those aged 20-40 years. The infection rate of babA2 genotype was highest [23(47.9%)] in those aged 41-60 years, and lowest [12(25.0%)] in those aged 61-80 years. Male patients were under a higher [28(53.9%) and 26(54.2%)] rate of infection with oipA and babA2, and female patients has a higher [40(55.6%)] rate of infection with babB. Among Hp-infected patients with digestive diseases, babB genotype was mainly found in patients with chronic superficial gastritis[17(58.6%)], duodenal ulcer[17(85.0%)], chronic atrophic gastritis[19(59.4%)] and gastric ulcer[16(72.7%)], while oipA genotype was mainly found in patients with gastric cancer[8(61.5%)]. CONCLUSIONS: Chronic superficial gastritis, duodenal ulcer, chronic atrophic gastritis, and gastric ulcer may have a close bearing on babB genotype infection, while oipA genotype infection may be associated with gastric cancer.
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Úlcera Duodenal , Gastrite Atrófica , Helicobacter pylori , Doenças Musculoesqueléticas , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Feminino , Masculino , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Helicobacter pylori/genética , Estudos Retrospectivos , GenótipoRESUMO
Background and Aims: Cryptozoospermia is an extreme oligozoospermia with an unsatisfactory treatment effect, with an incidence rate of approximately 8.73% in male infertility, whose effective solution has become the call of the times. Western Medicine has achieved certain effects through drugs, surgery, and assisted reproductive therapy, but this is still not ideal. Traditional Chinese medicine (TCM) has made many achievements in other disciplines; however, there is still a lack of evidence-based medical evidence to improve sperm production. Methods: The relevant literatures from the China National Knowledge Internet (CNKI) and PubMed in the past 10 years were collected in this article, of which the mechanisms, advantages, or current controversies of various treatment methods of Western Medicine and TCM were analyzed, to find new treatment methods and research directions. Results: With the development of modern science and technology, medical treatments for cryptozoospermia have become increasingly abundant; however, there is still no universally recognized unified and effective guiding plan. Although TCM has not been fully verified by evidence-based medicine, most TCM combined with Western Medicine can achieve unexpected results. Conclusion: The combination of TCM and Western Medicine may become a bane for cryptozoospermia and bring good news to infertile men worldwide.
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Abdominal adhesion and tumor recurrence are two thorny problems in the postoperative treatment of abdominal tumors. Although important progress has been made in the application of hydrogels in adjuvant therapy after tumor surgery, most of the products can not effectively combine the prevention of abdominal adhesion and the removal of residual cancer cells. In this study, a nanocomposite hydrogel (Col-APG-Cys@HHD) was prepared by crosslinking collagen and recombinant albumin nanoparticles (HHD NPs) with aldehydeylated polyethylene glycol (APG6K) followed by immobilizing zwitterionic cysteine (Cys) to one surface. One surface of the hydrogel adhered to the postoperative wound due to the adhesive properties of collagen, while the other surface coated with cysteine formed a hydration layer to hinder the stick of proteins and cells, thereby reducing the adhesion between tissues. Additionally, Col-APG-Cys@HHD hydrogel disintegrated under acidic condition and released HHD NPs that targeted into cancer cells and released drugs in response to low pH environment. The in vivo experiments' results demonstrated that Col-APG-Cys@HHD hydrogel could prevent intraperitoneal adhesions and inhibit tumor growth with minimal side effects, providing a potential strategy for the hydrogel-based drug delivery system in postoperative adjuvant therapy of tumors. STATEMENT OF SIGNIFICANCE: Tissue adhesion and tumor recurrence usually occur after abdominal tumor surgery. Hydrogels have been widely studied in adjuvant treatment of abdominal tumors, but their synergy in terms of controllable drug release and anti-peritoneal adhesion still needs to be improved. Herein, a nanocomposite hydrogel (Col-APG-Cys@HHD) was designed and constructed with one side that was tissue adhesive and the other side as antifouling. Additionally, the Col-APG-Cys@HHD hydrogel showed controlled drug release behavior in response to a pH gradient (6.5 to 5.5). This was conducive to its dissociation in an acidic tumor environment followed by the release of nanoparticles that entered into tumor cells and delivered docetaxel . To sum up, the Col-APG-Cys@HHD hydrogel demonstrated synergistic therapy for prevention of abdominal adhesion and tumor recurrence after abdominal tumor surgery.
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Neoplasias Abdominais , Cisteína , Humanos , Nanogéis , Aderências Teciduais/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Hidrogéis/farmacologia , Hidrogéis/química , Concentração de Íons de HidrogênioRESUMO
Purpose: In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo. Methods: Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS). Results: CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo. Conclusion: These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Cucumis sativus , Neoplasias Pulmonares , Triterpenos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de SinaisRESUMO
To overcome the low efficacy of conventional monotherapeutic approaches that use a single drug, functional nanocarriers loaded with an amalgamation of anticancer drugs have been promising in cancer therapy. Herein, aloe-derived nanovesicles (gADNVs) are modified with an active integrin-targeted peptide (Arg-Gly-Asp, RGD) by the postinsertion technique to deliver indocyanine green (ICG) and doxorubicin (DOX) for efficient breast cancer therapy. We presented for the first time that the π-π stacking interaction can turn the "competitive" relationship of ICG and DOX inside gADNVs into a "cooperative" relationship and enhance their loading efficiency. The dual-drug codelivery nanosystem, denoted as DIARs, was well stable and leakproof, exhibiting high tumor-targeting capability both in vitro and in vivo. Meanwhile, this nanosystem showed significant inhibition of cell growth and migration and induced cell apoptosis with the combination of phototherapy and chemotherapy. Intravenous administration of DIARs exhibited high therapeutic efficacy in a 4T1 tumor-bearing mouse model and exhibited no obvious damage to other organs. Overall, our DIAR nanosystem constitutively integrated the natural and economical gADNVs, π-π stacking interaction based on efficient drug loading, and tumor-targeted RGD modification to achieve an effective combination therapy for breast cancer.
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Aloe , Antineoplásicos , Nanopartículas , Neoplasias , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Verde de Indocianina/farmacologia , Camundongos , Neoplasias/tratamento farmacológico , OligopeptídeosRESUMO
In this work, we designed new dual-mode "turn-on" electrochemical (EC) and photoelectrochemical (PEC) sensors for the detection of dopamine (DA) based on 0D/2D/2D CuInS2/ZnS quantum dot (QD)-black phosphorous nanosheet (BPNS)-TiO2 nanosheet (TiO2NS) nanocomposites. QDs can not only improve the photocurrent of the developed PEC sensors, but also provide the electrochemical signal in the EC detection. BPNSs as p-type semiconductor with high conductive properties work as electron acceptors and are utilized to improve the sensitivity of the DA PEC and EC sensors. Under irradiation of visible light or the applied voltage, DA is both excited and releases electrons, realizing "turn-on" detection. The PEC sensors have a linear range of 0.1-100 µM with a lower detection limit of 0.028 µM. For the EC detection, BPNSs can accelerate electron transfer which attribute to its excellent conductivity. In the range of 1-200 µM, the working curve of DA detection by the EC sensors was established and the detection limit is 0.88 µM. Comparing the two methods, the PEC sensors have a lower detection limit, and the EC sensors have a wider monitoring range. The dual-mode sensors of EC and PEC pave an effective way for the detection in biological and medical fields.
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Cobre/química , Dopamina/análise , Nanoestruturas/química , Fósforo/química , Pontos Quânticos/química , Sulfetos/química , Titânio/química , Compostos de Zinco/química , Dopamina/urina , Técnicas Eletroquímicas/métodos , Humanos , Limite de DetecçãoRESUMO
BACKGROUND: Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. RESULTS: Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. CONCLUSIONS: Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.
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Aloe/química , Verde de Indocianina/química , Nanoestruturas/química , Aloe/metabolismo , Animais , Antioxidantes/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Estabilidade de Medicamentos , Hemólise/efeitos dos fármacos , Humanos , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Lipossomos/química , Melanoma Experimental/tratamento farmacológico , Camundongos , Nanoestruturas/uso terapêutico , Nanoestruturas/toxicidade , Tamanho da PartículaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic foot ulcer is one of the most serious complications of diabetes. Effective medical treatment regarding improvement of ulcer healing in patients is essential. Pien Tze Huang (PZH), a valuable Chinese traditional medicine, has been found significant efficacy on the curing of diabetic wound in clinic recently. AIM OF THE STUDY: This work was conducted to confirm the efficacy, and compare the therapeutic effect through the oral administration and local delivery route, providing a rationale for the new PZH form development; besides, the mechanisms through which PZH promoted the wound healing was also discussed. MATERIALS AND METHODS: First, the chemical composition of PZH was characterized by 1H-NMR and HPLC. The anti-apoptosis effects of PZH on high concentration glucose injured epidermal fibroblast (HFF-1) was investigated in a dose dependent way. Then, the effects of the systematical administration of PZH, and the topical used route on excisional wounds of Streptozotocin (STZ) induced diabetic mice were compared. RESULTS: The results illustrated that PZH decreased the reactive oxygen species (ROS) levels in cells, preventing cell damage/apoptosis through an ROS/Bcl-2/Bax/Caspase-3 pathway. The in vivo study proved that topical use of PZH exceeded the systematical route both in accelerating the wound closure and improving the healing quality. Meanwhile, PZH promoted wound closure through stimulating the secretion of Col-I, decreasing fibroblast apoptosis, and enhancing myo-fibroblast differentiation, in consistent with the mechanism study in vitro. CONCLUSIONS: Local used PZH improves wound healing by inhibiting the abnormal HFF-1 apoptosis and senescence. The study held a great promise for development of a topical dosage form of PZH for diabetic wound healing.
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Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Administração Cutânea , Administração Oral , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Glicemia/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Medicamentos de Ervas Chinesas/administração & dosagem , Fibroblastos/metabolismo , Fibroblastos/patologia , Masculino , Camundongos Endogâmicos C57BL , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Espécies Reativas de Oxigênio/metabolismo , Pele/lesões , Pele/metabolismo , Pele/patologia , Estreptozocina , Fatores de Tempo , Ferimentos e Lesões/complicações , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologiaRESUMO
BACKGROUND: Patient-derived organoid (PDO) models are highly valuable and have potentially widespread clinical applications. However, limited information is available regarding organoid models of non-small cell lung cancer (NSCLC). This study aimed to characterize the consistency between primary tumors in NSCLC and PDOs and to explore the applications of PDOs as preclinical models to understand and predict treatment response during lung cancer. METHODS: Fresh tumor samples were harvested for organoid culture. Primary tumor samples and PDOs were analyzed via whole-exome sequencing. Paired samples were subjected to immunohistochemical analysis. There were 26 antineoplastic drugs tested in the PDOs. Cell viability was assessed using the Cell Titer Glo assay 7-10 days after drug treatment. A heatmap of log-transformed values of the half-maximal inhibitory concentrations was generated on the basis of drug responses of PDOs through nonlinear regression (curve fit). A total of 12 patients (stages I-III) were enrolled, and 7 paired surgical tumors and PDOs were analyzed. RESULTS: PDOs retained the histological and genetic characteristics of the primary tumors. The concordance between tumors and PDOs in mutations in the top 20 NSCLC-related genes was >80% in five patients. Sample purity was significantly and positively associated with variant allele frequency (Pearson r = 0.82, P = 0.0005) and chromosome stability. The in vitro response to drug screening with PDOs revealed high correlation with the mutation profiles in the primary tumors. CONCLUSIONS: PDOs are highly credible models for detecting NSCLC and for prospective prediction of the treatment response for personalized precision medicine. KEY POINTS: Lung cancer organoid models could save precious time of drug testing on patients, and accurately select anticancer drugs according to the drug sensitivity results, so as to provide a powerful supplement and verification for the gene sequencing.
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Carcinoma Pulmonar de Células não Pequenas/genética , Avaliação Pré-Clínica de Medicamentos/métodos , Genômica/métodos , Neoplasias Pulmonares/genética , Organoides/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Dendritic macromolecules are potential candidates for nanomedical application. Herein, glycogen, the natural hyperbranched polysaccharide with favorable biocompatibility, is explored as an effective drug vehicle for treating liver cancer. In this system, glycogen is oxidized and conjugated with cancer drugs through a disulfide link, followed by in situ loading of polypyrrole nanoparticles and then coated with functional phospholipids to form the desired system, Gly-ss-DOX@ppy@Lipid-RGD. The phospholipid layer has good cell affinity and can assist the system to penetrate into cells smoothly. Additionally, combined with the "fusion targeting" of glycogen and the active targeting effect of RGD toward liver cancer cells, Gly-ss-DOX@ppy@Lipid-RGD presents efficient specificity and enrichment of hepatocellular carcinoma. Owing to the glutathione-triggered cleavage of disulfide linkers, Gly-ss-DOX@ppy@Lipid-RGD can controllably release drugs to induce cell nucleus damage. Meanwhile, the polypyrrole nanoparticles can absorb near-infrared light and radiate heat energy within tumors. Besides enhancing drug release, the heat can also provide photothermal treatment for tumors. As proved by in vitro and in vivo experiments, Gly-ss-DOX@ppy@Lipid-RGD is a remarkable candidate for synergistic chemophotothermal therapy with high anticancer therapeutic activity and reduced systematic toxicity, efficiently suppressing tumor growth. All results demonstrate that glycogen nanoparticles are expected to be a new building block for accurate hepatocellular carcinoma treatment.
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Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/uso terapêutico , Glicogênio/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Glicogênio/toxicidade , Hemólise/efeitos dos fármacos , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Fosfolipídeos/química , Fosfolipídeos/toxicidade , Fotoquimioterapia , Polímeros/química , Polímeros/efeitos da radiação , Polímeros/toxicidade , Pirróis/química , Pirróis/efeitos da radiação , Pirróis/toxicidadeRESUMO
Rapid, highly sensitive detection of tau protein and other neurodegenerative biomarkers remains a significant hurdle for diagnostic tests for Alzheimer's disease. In this work, we developed a novel tyrosinase (TYR)-induced tau aptamer-tau-tau antibody (anti-tau) sandwich fluorescence immunoassay to detect tau protein that used dopamine (DA)-functionalized CuInS2/ZnS quantum dots as the fluorophore. CuInS2/ZnS core/shell quantum dots with high luminescence, low toxicity, and excellent biocompatibility were successfully fabricated and decorated with DA through amide conjugation. Meanwhile, TYR was conjugated with anti-tau by a click reaction. When DA-functionalized CuInS2/ZnS quantum dots were added to the sandwich system, TYR catalyzed the transformation of DA to dopamine quinone, which acted as an effective electron acceptor and triggered fluorescence quenching. The fluorescence intensity of the immunoassay based on DA-functionalized CuInS2/ZnS quantum dots shows good performance in terms of linearity with the logarithm of tau protein concentration, with a linear concentration range from 10 pM to 200 nM. This work is the first to use a TYR-induced fluorescence immunoassay for the rapid detection of tau protein, paving a new way for the detection of disease biomarkers. Graphical abstract.
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Cobre/química , Imunofluorescência/métodos , Índio/química , Monofenol Mono-Oxigenase/química , Pontos Quânticos/química , Selênio/química , Sulfetos/química , Compostos de Zinco/química , Proteínas tau/análise , Cristalografia por Raios X , Dopamina/análogos & derivados , Dopamina/química , Microscopia Eletrônica de Transmissão , Análise Espectral/métodosRESUMO
CpG oligodeoxynucleotides (CpG ODNs) possess strong immunostimulatory activity, which hold great promise in cancer immunotherapy. However, their therapeutic efficacy is largely limited due to nuclease degradation and poor cellular internalization. Efficiently delivering CpG ODNs into target cells is crucial to improve their therapeutic efficacy. Boron nitride nanospheres (BNNS) possess advantage as carriers for CpG ODNs. However, their poor aqueous dispersity and low CpG ODN loading capacity became a big obstacle for further applications. Herein, we develop amino group grafted, mesoporous silica (MS)-functionalized BNNS as novel nanovectors for CpG ODN delivery. Modification of BNNS with MS significantly improved the dispersity of BNNS and CpG ODN loading. BNNS@MS-NH2 exhibited no cytotoxicity and enhanced the delivery of CpG ODNs into macrophages. BNNS@MS-NH2/CpG ODN complexes triggered enhanced immunostimulation and induced higher amounts of cytokines. Most importantly, BNNS@MS-NH2/CpG ODN complexes induced bifurcated cytokines, which simultaneously simulated the secretion of IL-6, TNF-α and IFN-α. In contrast, CpG ODN and BNNS/CpG ODN complexes could not. The result of the Transwell plate assay suggested that BNNS@MS-NH2/CpG ODN complexes were more effective in inhibiting cancer cell growth. Taken together, our findings provide a promising strategy for enhancing CpG ODN-mediated cancer immunotherapy.
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Sistemas de Liberação de Medicamentos , Imunoterapia , Nanosferas/química , Oligodesoxirribonucleotídeos/farmacologia , Dióxido de Silício/química , Adjuvantes Imunológicos , Animais , Linhagem Celular Tumoral , Interferon-alfa/sangue , Interleucina-6/sangue , Macrófagos/efeitos dos fármacos , Camundongos , Células RAW 264.7 , Fator de Necrose Tumoral alfa/sangueRESUMO
Dictyophora indusiata, an edible mushroom, is widely used not only as health foods but also as traditional Chinese medicine. This study aimed to investigate the molecular mechanism involved in the immunostimulatory activity of a polysaccharide from Dictyophora indusiata (DIP) in RAW264.7 cells. Results indicated that DIP induced the up-regulation of nitric oxide (NO), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor (TNF-α) production as well as the mRNA expression levels of iNOS, IL-1ß, IL-6 and TNF-α in macrophages. Furthermore, the functional blocking antibodies against TLR4 could markedly suppress DIP-mediated NO, IL-1ß, IL-6 and TNF-α production. Flow cytometry and confocal laser-scanning microscopy analyses confirmed that DIP could bind specifically to target cells, and the binding could be inhibited by anti-TLR4 monoclonal antibodies. The expression of nuclear factor kappa B (NF-κB) p65 was significantly induced by DIP. Therefore, the DIP-induced macrophage activation may be mediated via the TLR4/NF-κB signalling pathway.
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Adjuvantes Imunológicos/farmacologia , Agaricales/química , Polissacarídeos Fúngicos/farmacologia , Macrófagos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adjuvantes Imunológicos/química , Animais , Linhagem Celular , Polissacarídeos Fúngicos/química , Camundongos , Monocinas/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
A water-soluble polysaccharide named DI was extracted from the fruiting bodies of gastroid mushroom Dictyophora indusiata with boiling water. The chemical and physical characteristics of DI were investigated by a combination of chemical and instrumental analysis methods. The immunomodulatory activities on RAW 264.7 macrophage of DI in vitro were also studied. The results showed that DI is a ß-(1â3)-glucan with side branches of ß-(1â6)-glucosyl units, and it has triple-helical structure. DI has no toxic effect on cells, but can promote macrophage multiplication. DI significantly affects the immune function by promoting the production of nitric oxide and cytokines, such as tumor necrosis factor-α, interleukin-1, -6, and -12, showing an obvious dose-effect relationship. This work extends the application scope of the polysaccharide from D. indusiata in the biomedical field.
Assuntos
Basidiomycota/química , Produtos Biológicos/farmacologia , Polissacarídeos Fúngicos/farmacologia , Imunidade/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , beta-Glucanas/farmacologia , Animais , Citocinas/metabolismo , Carpóforos , Polissacarídeos Fúngicos/química , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7 , beta-Glucanas/químicaRESUMO
This paper has presented a novel strategy to carry out direct and sensitive determination of antitumor herbal drug aloe-emodin in complex matrices based on the graphene-Nafion modified glassy carbon (GN/GC) electrode. This proposed modified electrode showed good electrochemical response towards aloe-emodin (AE). Compared with the multiwall carbon nanotubes (MWCNTs) modified electrode, the GN/GC electrode has the advantages of higher sensitivity and lower cost. Under the optimized conditions, the calibration curve for AE concentration was linear in the range from 5 nmol/L to 1 µmol/L with the detection limit of 2 nmol/L. In addition, the practical analytical performance of the GN/GC electrode was examined by evaluating the selective detection of AE in natural aloe extracts and human urine samples with satisfied recovery. Therefore, the GN/GC electrode may hold great promise for fast, simple and sensitive detection and biomedical analysis of AE in complex matrices.
Assuntos
Antraquinonas/química , Antineoplásicos/farmacologia , Grafite/química , Preparações de Plantas/farmacologia , Técnicas Biossensoriais/métodos , Calibragem , Química Farmacêutica/métodos , Eletroquímica/métodos , Eletrodos , Polímeros de Fluorcarboneto/química , Microscopia de Força Atômica/métodos , Modelos Químicos , Nanotubos de Carbono/química , OxirreduçãoRESUMO
Using a single-walled carbon nanotubes (SWCNTs) as stationary phase of solid-phase microextraction (SPME) fibers, a simple, low cost and environmentally friendly method for extraction of 13 pesticides in Tea samples has been developed following gas chromatography-mass spectrometric determination. Potential factors affecting the extraction efficiency were investigated and optimized, including extraction and desorption time, extraction temperature, stirring rate, solution pH and ionic strength. Under optimized conditions, the linearity of the developed method was in the range of 0.125-25 ng/mL with correlation coefficients greater than 0.9928 and the limits of detections (LODs) were 0.027-0.23 ng/mL (S/N=3). Meanwhile, the relative standard deviations (RSDs) for five successive measurements with single fiber, fiber-to-fiber, day-to-day were 2.3-13.0, 8.2-14.6 and 4.1-12.5%, respectively, indicating good reproducibility of the proposed method. The fiber had high extraction efficiency for studied pesticides in comparison with commercial poly(dimethylsiloxane) (PDMS) and polyacrylate (PA) fibers and could be used for more than 70 times without decrease of efficiency. The developed method was successfully applied for the analysis of real samples including green Tea, oolong Tea, white Tea, and flower Tea, and the recoveries of the pesticides spiked in these samples ranged from 75.1 to 118.4%. Chlorfenapyr and lambda-cyhalothrin were found in the Tea samples bought randomly from local market. The results demonstrated that the developed SWCNTs-SPME method was a simple, efficient pretreatment and enrichment procedure for pesticides in complex matrices.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Nanotubos de Carbono , Praguicidas/análise , Microextração em Fase Sólida/métodos , Chá/química , Contaminação de Alimentos/análise , Nitrilas/análise , Piretrinas/análise , Reprodutibilidade dos TestesRESUMO
A new strategy for development of electrochemical DNA biosensor based on site-specific DNA cleavage of restriction endonuclease and using quantum dots as reporter was reported in this paper. The biosensor was fabricated by immobilizing a capture hairpin probe, thiolated single strand DNA labeled with biotin group, on a gold electrode. BfuCI nuclease, which is able to specifically cleave only double strand DNA but not single strand DNA, was used to reduce background current and improve the sensitivity. We demonstrated that the capture hairpin probe can be cleaved by BfuCI nuclease in the absence of target DNA, but cannot be cleaved in the presence of target DNA. The difference before and after enzymatic cleavage was then monitored by electrochemical method after the quantum dots were dissolved from the hybrids. Our results suggested that the usage of BfuCI nuclease obviously improved the sensitivity and selectivity of the biosensor. We successfully applied this method to the sequence-selective discrimination between perfectly matched and mismatched target DNA including a single-base mismatched target DNA, and detected as low as 3.3 × 10(-14) M of complementary target DNA. Furthermore, our above strategy was also verified with fluorescent method by designing a fluorescent molecular beacon (MB), which combined the capture hairpin probe and a pair of fluorophore (TAMRA) and quencher (DABCYL). The fluorescent results are consistent with that of electroanalysis, further indicating that the proposed new strategy indeed works as we expected.