RESUMO
Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.
Assuntos
Adenina/análogos & derivados , Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologiaRESUMO
BACKGROUND: Sex difference exists in the prevalence of dementia and cognitive decline. The impacts of sex-specific reproductive risk factors across the lifespan on the risk of dementia or cognitive decline are still unclear. Herein, we conducted this systemic review and meta-analysis to finely depict the longitudinal associations between sex-specific reproductive factors and dementia or cognitive decline. METHODS: PubMed, EMBASE, and Cochrane Library were searched up to January 2023. Studies focused on the associations of female- and male-specific reproductive factors with dementia or cognitive decline were included. Multivariable-adjusted effects were pooled via the random effect models. Evidence credibility was scored by the GRADE system. The study protocol was pre-registered in PROSPERO and the registration number is CRD42021278732. RESULTS: A total of 94 studies were identified for evidence synthesis, comprising 9,839,964 females and 3,436,520 males. Among the identified studies, 63 of them were included in the meta-analysis. According to the results, seven female-specific reproductive factors including late menarche (risk increase by 15%), nulliparous (11%), grand parity (32%), bilateral oophorectomy (8%), short reproductive period (14%), early menopause (22%), increased estradiol level (46%), and two male-specific reproductive factors, androgen deprivation therapy (18%), and serum sex hormone-binding globulin (22%) were associated with an elevated risk of dementia or cognitive decline. CONCLUSIONS: These findings potentially reflect sex hormone-driven discrepancy in the occurrence of dementia and could help build sex-based precise strategies for preventing dementia.
Assuntos
Disfunção Cognitiva , Demência , Neoplasias da Próstata , Gravidez , Feminino , Masculino , Humanos , Demência/epidemiologia , Demência/complicações , Longevidade , Antagonistas de Androgênios , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Fatores de Risco , ParidadeRESUMO
Cancer immunotherapy, such as immune checkpoint blockade, chimeric antigen receptor, and cytokine therapy, has emerged as a robust therapeutic strategy activating the host immune system to inhibit primary and metastatic lesions. However, low tumor immunogenicity (LTI) and immunosuppressive tumor microenvironment (ITM) severely compromise the killing effect of immune cells on tumor cells, which fail to evoke a strong and effective immune response. As an exogenous stimulation therapy, phototherapy can induce immunogenic cell death (ICD), enhancing the therapeutic effect of tumor immunotherapy. However, the lack of tumor targeting and the occurrence of immune escape significantly reduce its efficacy in vivo, thus limiting its clinical application. Nanophotoimmunotherapy (nano-PIT) is a precision-targeted tumor treatment that co-loaded phototherapeutic agents and various immunotherapeutic agents by specifically targeted nanoparticles (NPs) to improve the effectiveness of phototherapy, reduce its phototoxicity, enhance tumor immunogenicity, and reverse the ITM. This review will focus on the theme of nano-PIT, introduce the current research status of nano-PIT on converting "cold" tumors to "hot" tumors to improve immune efficacy according to the classification of immunotherapy targets, and discuss the challenges, opportunities, and prospects.
Assuntos
Nanopartículas , Neoplasias , Humanos , Microambiente Tumoral , Imunoterapia , Neoplasias/terapia , Imunossupressores/farmacologia , Antígenos de Neoplasias , Nanopartículas/uso terapêutico , Linhagem Celular TumoralRESUMO
KEY MESSAGE: PtrANR1 positively regulates plant drought tolerance by increasing proline level and reducing ROS accumulation. PtrANR1 directly activates PtrAUX1 expression to promote root growth and improve plant drought tolerance. Citrus quality and yield are severely declined under drought stress. To date, the effects of MADS-box family transcription factors (TFs) on plant drought resistance have made some progress. However, whether MADS-box family TFs are associated with citrus drought response has remained unclear. The current paper identified a MADS-box family gene PtrANR1 encoding anthocyanidin reductase from trifoliate orange. PtrANR1 exhibits high identities with ANR1 proteins found in various plants. PtrANR1 possesses two conserved domains known as MADS and kertanin-like domains. PtrANR1 is a nuclear protein which has transactivation activity. A significant induction of PtrANR1 transcript was detected in leaves and roots of trifoliate orange treated with PEG6000 and ABA. Under drought stress, Arabidopsis ectopic overexpressing PtrANR1 exhibited obviously elevated contents of proline, ABA and IAA, better developed root, enhanced antioxidant enzyme activities, as well as notably reduced accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS) compared with WT plants. However, opposite change trends of these physiological indices were detected in PtrANR1 homolog silencing lemon. Furthermore, transgenic Arabidopsis displayed significantly increased expression levels in genes associated with ABA, IAA and proline production, IAA polar transport, ROS elimination and drought response. However, these genes exhibited noticeably decreased transcript levels in PtrANR1 homolog silencing lemon. Moreover, PtrANR1 could increase IAA content and promote root growth by binding to GArG-box in the promoter of PtrAUX1 to activate its transcript. These findings indicated that PtrANR1 had a beneficial impact on plant drought resistance through promoting root development, increasing proline accumulation and scavenging of ROS.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Secas , Plantas Geneticamente Modificadas/genética , Antioxidantes/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Prolina/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Arabidopsis/genéticaRESUMO
Numerous literatures have shown the advantages of Pickering emulsion (PE) for the delivery of bioactive ingredients in the fields of food, medicine, and cosmetics, among others. On this basis, the multi-loading mode of bioactives (internal phase encapsulation and/or loading at the interface) in small molecular bioactives nanocrystal-stabilized PE (BNC-PE) enables them higher loading efficiencies, controlled release, and synergistic or superimposed effects. Therefore, BNC-PE offers an efficacious delivery system. In this review, we briefly summarize BNC-PE fabrication and characterization, with a focus on the processes of possible evolution and absorption of differentially applied BNC-PE when interacting with the body. In addition, methods of monitoring changes and absorption of BNC-PE in vivo, from the nanomaterial perspective, are also introduced. The purpose of this review is to provide an accessible and comprehensive methodology for the characterization and evaluation of BNC-PE after formulation and preparation, especially in relation to biological assessment and detailed mechanisms throughout the absorption process of BNC-PE in vivo.
Assuntos
Nanopartículas , Nanoestruturas , EmulsõesRESUMO
OBJECTIVE: N6-methyladenosine (m6A) mRNA modification triggers malignant behaviors of tumor cells and thereby drives malignant progression in gastric cancer (GC). However, data regarding the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in GC are very limited in the literature. We aimed to investigate the prognostic potential of m6A-related lncRNAs in predicting prognosis and monitoring immunotherapy efficacy in GC patients. METHODS: Transcriptome and clinical data were obtained from GC biopsies from Cancer Genome Atlas (TCGA). M6A-related lncRNAs associated with GC were identified by constructing a co-expression network, and the gene pairs differentially expressed in GC were selected using univariate analysis. We constructed a risk model based on prognosis-related lncRNA pairs selected using the LASSO algorithm and quantified the best cutoff by comparing the area under the curve (AUC) for risk stratification. A risk model with the optimal discrimination between high- and low-risk GC patients was established. Its feasibility for overall survival prediction and discrimination of clinicopathological features, tumor-infiltrating immune cells, and biomarkers of immune checkpoint inhibitors between high- and low-risk groups were assessed. RESULTS: Finally, we identified 11 m6A-related lncRNA pairs associated with GC prognosis based on transcriptome analysis of 375 GC specimens and 32 normal tissues. A risk model was constructed with an AUC of 0.8790. We stratified GC patients into high- and low-risk groups at a cutoff of 1.442. As expected, patients in the low-risk group had longer overall survival versus the high-risk group. Infiltration of cancer-associated fibroblasts, endothelial cells, macrophages, particularly M2 macrophages, and monocytes was more severe in high-risk patients than low-risk individuals, who exhibited high CD4+ Th1 cell infiltration in GC. Altered expressions of immune-related genes were observed in both groups. PD-1 and LAG3 expressions were found higher in low-risk patients than high-risk patients. Immunotherapy, either single or combined use of PD-1 or CTLA4 inhibitors, had better efficacy in low-risk patients than high-risk patients. CONCLUSION: The new risk model based on a 11-m6A-related lncRNA signature can serve as an independent predictor for GC prognosis prediction and may aid in the development of personalized immunotherapy strategies for patients.
Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Células Endoteliais/metabolismo , Humanos , Imunoterapia , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapiaRESUMO
Drought limits citrus yield and fruit quality worldwide. The basic helix-loop-helix (bHLH) transcription factors (TFs) are involved in plant response to drought stress. However, few bHLH TFs related to drought response have been functionally characterized in citrus. In this study, a bHLH family gene, named PtrbHLH66, was cloned from trifoliate orange. PtrbHLH66 contained a highly conserved bHLH domain and was clustered closely with bHLH66 homologs from other plant species. PtrbHLH66 was localized to the nucleus and had transcriptional activation activity. The expression of PtrbHLH66 was significantly induced by polyethylene glycol 6000 (PEG6000) and abscisic acid (ABA) treatments. Ectopic expression of PtrbHLH66 promoted the seed germination and root growth, increased the proline and ABA contents and the activities of antioxidant enzymes, but reduced the accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS) under drought stress, resulting in enhanced drought tolerance of transgenic Arabidopsis. In contrast, silencing the PtrbHLH66 homolog in lemon plants showed the opposite effects. Furthermore, under drought stress, the transcript levels of 15 genes involved in ABA biosynthesis, proline biosynthesis, ROS scavenging and drought response were obviously upregulated in PtrbHLH66 ectopic-expressing Arabidopsis but downregulated in PtrbHLH66 homolog silencing lemon. Thus, our results suggested that PtrbHLH66 acted as a positive regulator of plant drought resistance by regulating root growth and ROS scavenging.
Assuntos
Arabidopsis , Poncirus , Arabidopsis/metabolismo , Poncirus/genética , Poncirus/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Resistência à Seca , Estresse Fisiológico/genética , Ácido Abscísico/metabolismo , Secas , Prolina/metabolismoRESUMO
Drought is one of the main abiotic stresses limiting the quality and yield of citrus. Cuticular waxes play an important role in regulating plant drought tolerance and water use efficiency (WUE). However, the contribution of cuticular waxes to drought tolerance, WUE and the underlying molecular mechanism is still largely unknown in citrus. 'Longhuihong' (MT) is a bud mutant of 'Newhall' navel orange with curly and bright leaves. In this study, significant increases in the amounts of total waxes and aliphatic wax compounds, including n-alkanes, n-primary alcohols and n-aldehydes, were overserved in MT leaves, which led to the decrease in cuticular permeability and finally resulted in the improvements in drought tolerance and WUE. Compared to WT leaves, MT leaves possessed much lower contents of malondialdehyde (MDA) and hydrogen peroxide (H2O2), significantly higher levels of proline and soluble sugar, and enhanced superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities under drought stress, which might reduce reactive oxygen species (ROS) damage, improve osmotic regulation and cell membrane stability, and finally, enhance MT tolerance to drought stress. Transcriptome sequencing results showed that seven structural genes were involved in wax biosynthesis and export, MAPK cascade, and ROS scavenging, and seven genes encoding transcription factors might play an important role in promoting cuticular wax accumulation, improving drought tolerance and WUE in MT plants. Our results not only confirmed the important role of cuticular waxes in regulating citrus drought resistance and WUE but also provided various candidate genes for improving citrus drought tolerance and WUE.
Assuntos
Citrus sinensis , Secas , Citrus sinensis/genética , Citrus sinensis/metabolismo , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transcriptoma , Água/metabolismo , Ceras/metabolismoRESUMO
Immunotherapy through stimulating the host immune system has emerged as a powerful therapeutic strategy for various malignant and metastatic tumors in the clinic. However, harnessing the immune system for cancer treatment often fails to obtain a durable response rate due to the poor immunogenicity and the strong immunosuppressive milieu in the tumor site. Herein, a redox-activated liposome was developed from the self-assembly of the porphyrin-phospholipid conjugate and coencapsulation of indoleamine 2,3-dioxygenase (IDO) inhibitor into the interior lumen via remote-loading for simultaneous induction of immunogenic cell death (ICD) and reversing of suppressive tumor microenvironment. The nanoparticle exhibited prolonged blood circulation and enhanced tumor accumulation in the 4T1 tumor-bearing mice after intravenous injection. The nanovesicle could render exponential activation of fluorescence signal and photodynamic therapy (PDT) activity (>100-fold) in response to the high level of intracellular glutathione after endocytosed by tumor cells, thereby achieving effective inhibition of tumor growth and reduced phototoxicity to normal tissues owing to the activatable design of the nanoparticle. More importantly, redox-activated PDT induced intratumoral infiltration of cytotoxic T lymphocytes by induction of ICD of tumor cells. After combining with the IDO inhibitor, the systemic antitumor immune response was further augmented. Hence, we believe that the present nanovesicle strategy has the potential for the synergistic immunotherapy of the metastatic cancers.
Assuntos
Inibidores Enzimáticos/uso terapêutico , Morte Celular Imunogênica/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Neoplasias Mamárias Animais/tratamento farmacológico , Nanopartículas/uso terapêutico , Porfirinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Feminino , Imunoterapia , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Lipossomos/uso terapêutico , Neoplasias Mamárias Animais/imunologia , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Oxirredução , Fotoquimioterapia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Microambiente Tumoral/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: To determine whether radical resection can benefit patients with advanced gallbladder adenocarcinoma using a Bayesian network (BN) with clinical data. METHODS: In total, 362 patients who had undergone surgical treatment of gallbladder adenocarcinoma at a tertiary institute were evaluated to establish two BN models using a tree-augmented naïve Bayes algorithm. We then chose 250 patients with T3-4N0-2M0 stage gallbladder adenocarcinoma to test the posterior probability after the surgical type was taken into account. RESULTS: In total, 170 patients (≤7 months) and 137 patients (>7 months) were correctly classified in the median survival time model (accuracy, 84.81%), and 204 patients (≤12 months), 15 patients (12-36 months), 17 patients (36-60 months), and 34 patients (>60 months) were correctly classified in the 1-, 3-, and 5-year survival model (accuracy, 74.59%), respectively. Every posterior probability in the two models upregulated the ratio of the longer survival time and suggested a better prognosis for gallbladder adenocarcinoma that can be improved by R0 resection. CONCLUSIONS: These BN models indicate that stages T4 and N2 gallbladder adenocarcinoma are not contraindications for surgery and that R0 resection can improve survival in patients with advanced gallbladder adenocarcinoma.
Assuntos
Adenocarcinoma/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias da Vesícula Biliar/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Teorema de Bayes , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Estadiamento de Neoplasias , ProbabilidadeRESUMO
BACKGROUND: This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC). METHODS: A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics. RESULTS: E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P < 0.050); moreover, the molecular subtypes were an independent factor influencing E-cad expression in early-stage IDCs. A total of 12 observational studies (including our study) were included in the meta-analysis. The meta-analytical results show a significantly greater risk of E-cad expression loss in triple-negative breast cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07). CONCLUSIONS: Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.
Assuntos
Neoplasias da Mama/patologia , Caderinas/metabolismo , Carcinoma Ductal de Mama/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Antígenos CD , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Estudos RetrospectivosRESUMO
Navel orange (Citrus sinensis [L.] Osbeck) fruit surfaces contain substantial quantities of cuticular waxes, which have important eco-physiological roles, such as water retention and pathogen defense. The wax constituents of ripe navel orange have been studied in various reports, while the wax changes occurring during fruit development and the molecular mechanism underlying their biosynthesis/export have not been investigated. Recently, we reported a spontaneous bud mutant from the wild-type (WT) 'Newhall' Navel orange. This mutant displayed unusual glossy fruit peels and was named 'glossy Newhall' (MT). In this study, we compared the developmental profiles of the epicuticular and intracuticular waxes on the WT and MT fruit surfaces. The formation of epicuticular wax crystals on the navel orange surface was shown to be dependent on the accumulation of high amounts of aliphatic wax components with trace amounts of terpenoids. In sharp contrast, the underlying intracuticular wax layers have relatively low concentrations of aliphatic wax components but high concentrations of cyclic wax compounds, especially terpenoids at the late fruit developmental stages. Our work also showed that many genes that are involved in wax biosynthesis and export pathways were down-regulated in MT fruit peels, leading to a decrease in aliphatic wax component amounts and the loss of epicuticular wax crystals, ultimately causing the glossy phenotype of MT fruits.
Assuntos
Citrus sinensis/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Ceras/metabolismo , Transporte Biológico , Citrus sinensis/genética , Frutas/metabolismo , Frutas/ultraestrutura , Mutação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
To investigate the apoptotic mechanism of triple-negative breast cancer (TNBC) cells induced by gefitinib and PI3K inhibitor SF1126. MDA-MB-231, MDA-MB-436, and MCF-7 cells were incubated with 0.1 µmol/l gefitinib, 1 µmol/l gefitinib, 10 µmol/l gefitinib, 1 µmol/l SF1126, 0.1 µmol/l gefitinib+1 µmol/l SF1126, 1 µmol/l gefitinib+1 µmol/l SF1126, and 10 µmol/l gefitinib+1 µmol/l SF1126. Then, cell viability and survival were determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining. The apoptosis-related factors and phosphoinositide-3-kinase/protein kinase B, the mammalian target of rapamycin (PI3K/AKT-mTOR) signaling pathway-related factors were detected by western blot. For TNBC cells, cell viability or survival was not significantly inhibited by gefitinib or SF1126 alone; however, marked cell apoptosis was noted in the gefitinib and SF1126 combination groups, and this effect was dose dependent. Also, the expressions of apoptosis markers, such as cleaved caspase-3, Bcl-2/Bax, were altered by the gefitinib and SF1126 combination. Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6-kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination, which may be responsible for the apoptosis. Gefitinib combined with SF1126 could induce cell apoptosis in TNBC cells and this effect was mediated through the EGFR-PI3K-AKT-mTOR-p70S6K pathway. Our studies have set the stage for future clinical trials of TNBC therapy by the combination of gefitinib and SF1126.
Assuntos
Apoptose/efeitos dos fármacos , Cromonas/farmacologia , Oligopeptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinazolinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Receptores ErbB/metabolismo , Feminino , Gefitinibe , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor ErbB-2/metabolismo , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
A novel surface imprinting polymer based on magnetic carbon nanotubes was prepared using dendritic polyethyleneimine as functional monomer to amplify the number of imprinted cavities. The characteristics of resulting polymers were evaluated by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM). Results suggest that magnetic nanoparticles are deposited onto the surface of multiwalled carbon nanotubes and the imprinted shell is coated on the surface of magnetic carbon nanotubes with a thickness of approximately 8 nm. Magnetic imprinted polymers are sensitive to magnetic fields and can be easily separated within 3 s using an external magnet. The adsorption results indicate that the obtained imprinted polymers have fast kinetics, an ultrahigh adsorption capacity of 479.9 mg g(-1), and satisfactory selectivity towards the template molecule. The prepared materials have excellent stability with no obvious deterioration after six adsorption-regeneration cycles. In addition, a method for determination of gallic acid (GA) in pomegranate rind was developed, using a combination of the prepared polymers used as solid-phase extraction (SPE) sorbents and high-performance liquid chromatography (HPLC) for rapid isolation and determination of GA. The limit of detection of the proposed method is 0.001 µg mL(-1), and the intra and inter-day relative standard deviations (RSDs) are lower than 3.8% and 5.3%, respectively. The recoveries of GA from pomegranate rind extract are in the range 98.2-103.6% with RSDs lower than 4.3%.
Assuntos
Ácido Gálico/isolamento & purificação , Lythraceae/química , Imãs/química , Impressão Molecular/métodos , Nanotubos de Carbono/química , Polietilenoimina/química , Extração em Fase Sólida/métodos , Adsorção , Cromatografia Líquida de Alta Pressão/métodosRESUMO
A novel magnetic core-shell polydopamine-cupric ion complex imprinted polymer was prepared in one-step through surface imprinting technology, which could specifically recognize bovine hemoglobin from the real blood samples. The polymerization conditions and adsorption performance of the resultant nanomaterials were investigated in detail. The results showed that the cupric ion played an important role in the recognition of template proteins. The saturating adsorption capacity of this kind of imprinted polymers was 2.23 times greater than those of imprinted polymers without cupric ion. The imprinting factor of the imprinted materials was as high as 4.23 for the template molecule. The selective separation bovine hemoglobin from the real blood sample is successfully applied. In addition, the prepared materials had excellent stability and no obvious deterioration after five adsorption-regeneration cycles. Easy preparation, rapid separation, high binding capacity and satisfactory selectivity for the template protein make this polymer attractive in the separation of high-abundance proteins.
Assuntos
Cobre/química , Dopamina/química , Hemoglobinas/análise , Indóis/química , Nanopartículas de Magnetita/química , Impressão Molecular , Polímeros/química , Adsorção , Animais , Bovinos , Hemoglobinas/química , Íons/química , Estrutura MolecularRESUMO
Novel core-shell dual-template molecularly imprinted superparamagnetic nanoparticles were synthesized using bovine hemoglobin and bovine serum albumin as the templates for the efficient depletion of these two high-abundance proteins from blood plasma for the first time. The preparation process combined surface imprinting technique and a two-step immobilized template strategy. The obtained polymers were fully characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The results showed that the as-synthesized nanomaterials possessed homogeneous and thin imprinted shells with a thickness of about 5 nm, stable crystalline phase, and superparamagnetism. The binding performance of the imprinted polymers was investigated through a series of adsorption experiments, which indicated that the products had satisfactory recognition ability for bovine hemoglobin and bovine serum albumin. The resultant nanoparticles were also successfully applied to simultaneously selective removal of two proteins from a real bovine blood sample.
RESUMO
Cancer immunotherapy is expected to achieve tumor treatment mainly by stimulating the patient's own immune system to kill tumor cells. However, the low immunogenicity of the tumor and the poor efficiency of tumor antigen presentation result in a variety of solid tumors that do not respond to immunotherapy. Herein, we designed a proton-gradient-driven porphyrin-based liposome (PBL) with highly efficient Toll-like receptor 7 (TLR7) agonist (imiquimod, R837) encapsulation (R837@PBL). R837@PBL rapidly released R837 in the acid microenvironment to activate the TLR in the endosome inner membrane to promote bone-marrow-derived dendritic cell maturation and enhance antigen presentation. R837@PBL upon laser irradiation triggered immunogenic cell death of tumor cells and tumor-associated antigen release after subcutaneous injection, activated TLR7, formed in situ tumor nanoadjuvants, and enhanced the antigen presentation efficiency. Photoimmunotherapy promoted the infiltration of cytotoxic T lymphocytes into tumor tissues, inhibited the growth of the treated and abscopal tumors, and exerted highly effective photoimmunotherapeutic effects. Hence, our designed in situ tumor nanoadjuvants are expected to be an effective treatment for treated and abscopal tumors, providing a novel approach for synergistic photoimmunotherapy of tumors.
Assuntos
Neoplasias , Porfirinas , Humanos , Imiquimode/farmacologia , Lipossomos/farmacologia , Receptor 7 Toll-Like/agonistas , Prótons , Porfirinas/farmacologia , Neoplasias/terapia , Imunoterapia , Adjuvantes Imunológicos/farmacologia , Antígenos de Neoplasias , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
Curcumin (Cur) as a natural pigment and biological component, can be widely used in food and beverages. However, the water insolubility of Cur significantly limits its applications. In this study, we prepared a series of nanocrystals via ultrasound-assisted method to improve the solubility and availability of Cur. The results showed artemisia sphaerocephala krasch polysaccharide (ASKP), gum arabic (GA) and wheat protein (WP) were outstanding stabilizers for nanocryatals except traditional agent, poloxamer 188 (F68). The obtained curcumin nanocrystals (Cur-NC) displayed a rod-shaped, crystal- and nanosized structure, and extremely high loading capacity (more over 80 %, w/w). Compared with raw powder, Cur-NC greatly improved the water solubility and dispersibility, and the slow and complete release of Cur of Cur-NC also endowed them excellent antioxidant capacities even at 10 µg/mL. Importantly, as functional factor additive in beverages (e.g. water and emulsion), Cur-NC could increase the content of Cur to at least 600 µg/mL and retain a good stability. Overall, we provided an effective improvement method for the liposoluble active molecules (e.g. Cur) based on the nanocrystals, which not only tremendously enhanced its water solubility, but also strengthened its bioactivity. Notably, our findings broadened the application of water-insoluble compounds.
Assuntos
Curcumina , Nanopartículas , Curcumina/farmacologia , Curcumina/química , Solubilidade , Poloxâmero/química , Nanopartículas/química , Água/química , Tamanho da PartículaRESUMO
The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an "active PC" to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of "passive PCs" formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.