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Cardiovascular diseases are disorders of the heart and vascular system that cause high mortality rates worldwide. Vascular endothelial cell (VEC) injury caused by oxidative stress (OS) is an important event in the development of various cardiovascular diseases, including ischemic heart disease. This study aimed to investigate the critical roles and molecular mechanisms of long non-coding RNA (lncRNA) SNHG16 in regulating vascular endothelial cell injury under oxidative stress. We demonstrated that SNHG16 was significantly downregulated and miRNA-23a-3p was notably induced in human vascular endothelial cells under OS. Overexpressing SNHG16 or silencing miR-23a-3p effectively mitigated the OS-induced VEC injury. Additionally, glutamine metabolism of VECs was suppressed under OS. SNHG16 protected the OS-suppressed glutamine metabolism, while miR-23a-3p functioned oppositely in VECs. Furthermore, SNHG16 downregulated miR-23a-3p by sponging miR-23a-3p, which direct targeted the glutamine metabolism enzyme, GLS. Finally, restoring miR-23a-3p in SNHG16-overexpressing VECs successfully reversed the protective effect of SNHG16 on vascular endothelial cell injury under OS. In summary, our results revealed the roles and molecular mechanisms of the SNHG16-mediated protection against VEC injury under OS by modulating the miR-23a-3p-GLS pathway.
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The cell transition from an inflammatory phase to a subsequent proliferative phase is crucial for wound healing, yet the driving mechanism remains unclear. By profiling lncRNA expression changes during human skin wound healing and screening lncRNA functions, we identify SNHG26 as a pivotal regulator in keratinocyte progenitors underpinning this phase transition. Snhg26-deficient mice exhibit impaired wound repair characterized by delayed re-epithelization accompanied by exacerbated inflammation. Single-cell transcriptome analysis combined with gain-of-function and loss-of-function of SNHG26 in vitro and ex vivo reveals its specific role in facilitating inflammatory-to-proliferative state transition of keratinocyte progenitors. A mechanistic study unravels that SNHG26 interacts with and relocates the transcription factor ILF2 from inflammatory genomic loci, such as JUN, IL6, IL8, and CCL20, to the genomic locus of LAMB3. Collectively, our findings suggest that lncRNAs play cardinal roles in expediting tissue repair and regeneration and may constitute an invaluable reservoir of therapeutic targets in reparative medicine.
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Proliferação de Células , Queratinócitos , RNA Longo não Codificante , Células-Tronco , Cicatrização , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Queratinócitos/metabolismo , Animais , Humanos , Cicatrização/genética , Proliferação de Células/genética , Células-Tronco/metabolismo , Camundongos , Inflamação/genética , Inflamação/patologia , Inflamação/metabolismo , Pele/patologia , Pele/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BL , MasculinoRESUMO
Against the backdrop of the Ministry of Education's promotion of new agricultural science construction and interdisciplinary integration, a comprehensive chemistry experiment to enhance the practical skills of students in preparing biomass functional materials and detecting pesticide residues was designed. Natural loofah was utilized as a precursor in synthesizing nitrogen-doped magnetic porous carbon materials, which were then applied in a magnetic solid-phase extraction (MSPE) technique. Subsequently, high performance liquid chromatography (HPLC) was employed to analyze and detect the phenylurea herbicide monuron in tea. The experimental process included material synthesis, characterization, optimization of the MSPE conditions, adsorption performance studies, and HPLC, reflecting its scientific, systematic nature and providing a comprehensive learning platform for students. It not only deepens student understanding of the relationship between material characterization and application, but also improves their experimental design and problem-solving capacities. Moreover, by integrating cutting-edge science, ideological and political education, and experimental training, it not only stimulates student interest in scientific research and cultivates innovative thinking and practical skills, but also strengthens their feelings of social responsibility and historical mission. This approach realizes the comprehensive educational goals of experimental training and lays the foundation for nurturing high-quality talent with a global perspective and sense of social responsibility.
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Herbicidas , Extração em Fase Sólida , Chá , Cromatografia Líquida de Alta Pressão , Chá/química , Herbicidas/análise , Compostos de Fenilureia/análise , Resíduos de Praguicidas/análiseRESUMO
Novel perovskites pertain to newly discovered or less studied variants of the conventional perovskite structure, characterized by distinctive properties and potential for diverse applications such as ferroelectric, optoelectronic, and thermoelectric uses. In recent years, advancements in computational methods have markedly expedited the discovery and design of innovative perovskite materials, leading to numerous pertinent reports. However, there are few reviews that thoroughly elaborate the role of computational methods in studying novel perovskites, particularly for state-of-the-art perovskite categories. This review delves into the computational discovery of novel perovskite materials, with a particular focus on antiperovskites and chalcogenide perovskites. We begin with a discussion on the computational methods applied to evaluate the stability and electronic structure of materials. Next, we highlight how these methods expedite the discovery process, demonstrating how rational simulations contribute to researching novel perovskites with improved performance. Finally, we thoroughly discuss the remaining challenges and future outlooks in this research domain to encourage further investigation. We believe that this review will be highly beneficial both for newcomers to the field and for experienced researchers in computational science who are shifting their focus to novel perovskites.
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Non-small cell lung cancer (NSCLC) remains the foremost contributor to cancer-related fatalities globally, with limited effective therapeutic modalities. Recent research has shed light on the role of ferroptosis in various types of cancers, offering a potential avenue for improving cancer therapy. Herein, we identified E3 ubiquitin ligase deltex 2 (DTX2) as a potential therapeutic target candidate implicated in promoting NSCLC cell growth by inhibiting ferroptosis. Our investigation revealed a significant upregulation of DTX2 in NSCLC cells and tissues, which was correlated with poor prognosis. Downregulation of DTX2 suppressed NSCLC cell growth both in vitro and in vivo, while its overexpression accelerated cell proliferation. Moreover, knockdown of DTX2 promoted ferroptosis in NSCLC cells, which was mitigated by DTX2 overexpression. Mechanistically, we uncovered that DTX2 binds to nuclear receptor coactivator 4 (NCOA4), facilitating its ubiquitination and degradation via the K48 chain, which subsequently dampens NCOA4-driven ferritinophagy and ferroptosis in NSCLC cells. Notably, DTX2 knockdown promotes cisplatin-induced ferroptosis and overcomes drug resistance of NSCLC cells. These findings underscore the critical role of DTX2 in regulating ferroptosis and NCOA4-mediated ferritinophagy, suggesting its potential as a novel therapeutic target for NSCLC.
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The nanozyme-based colorimetric sensor shows promise for rapid pesticide detection but struggles with non-specific enzyme inhibition. This study developed a portable paper-based sensor for detecting the propiconazole (PC) pesticide using Fe@PCN-224 nanocubes (NCs). Characterization confirmed the successful synthesis of Fe@PCN-224 NCs, which displayed peroxidase-like activity. The specific interaction between PC's triazole ring and the Fe active site inhibited their activity, enabling selective detection with a limit of 8 × 10-9 mol L-1 and a linear range of 0.03 × 10-6 to 0.90 × 10-6 mol L-1. Kinetic studies revealed a Michaelis-Menten constants (Km) of 0.68 × 10-3 mol L-1 for TMB, indicating higher affinity in Fe@PCN-224 NCs. The electron paramagnetic resonance (EPR) analysis revealed the production of â¢OH, 1O2, O2â¢- during the catalytic reactions. By integrating smartphone technology, this portable sensor achieved recoveries from vegetable samples between 94.6 % and 109.2 %, demonstrating its potential as an accurate, cost-effective analytical tool for food safety and advancing nanozyme applications.
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BACKGROUND: Skin wound healing involves a complex gene expression program that remains largely undiscovered in humans. Circular RNAs (circRNAs) and microRNAs (miRNAs) are key players in this process. OBJECTIVES: To understand the functions and potential interactions of circRNAs and miRNAs in human skin wound healing. METHODS: CircRNA, linear RNA, and miRNA expression in human acute and chronic wounds were analyzed using RNA sequencing and qRT-PCR. The roles of circASH1L(4,5) and miR-129-5p were studied in human primary keratinocytes (proliferation and migration assays, microarray analysis) and ex vivo wound models (histological analysis). The interaction between circASH1L(4,5) and miR-129-5p was examined using luciferase reporter and RNA pull-down assays. RESULTS: We identified circASH1L(4,5) and its interaction with miR-129-5p, both of which increased during human skin wound healing. Unlike typical miRNA sponging, circASH1L enhanced miR-129 stability and silencing activity by protecting it from target-directed degradation triggered by NR6A1 mRNA. TGF-ß signaling, crucial in wound healing, promoted circASH1L expression while suppressing NR6A1, thereby increasing miR-129 abundance at the post-transcriptional level. CircASH1L and miR-129 enhanced keratinocyte migration and proliferation, crucial for re-epithelialization of human wounds. CONCLUSIONS: Our study uncovers a novel role for circRNAs as protectors of miRNAs and highlights the importance of regulated miRNA degradation in skin wound healing.
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The heterotrophic nitrification-aerobic denitrification (HNAD) is a new biological denitrification technology, the present study isolated a new HNAD strain named Cupriavidus metallidurans TX6 with heavy metal resistance. The gene expression, electron transport, enzyme activity and nitrogen removal property of strain TX6 were studied with different influencing factors. Strain TX6 has five nitrogen metabolism pathways (NH4+ â NH2OH â NO â NO2- â NH4+ â GOGAT/GDH; NH4+-N â NH2OH â NO â N2O â N2; NH4+ â NH2OH â NO â NO2- â NO3-; NO3- â NO2- â NH4+ â GOGAT/GDH; NO3-â NO2- â NH4+ â GOGAT/GDH). Nitrogen balance analysis shows that 29 ± 4 mg/L of N was converted to intracellular nitrogen by assimilation and 50 ± 3 mg/L N loss may be attributed to aerobic denitrification. The results provide a theoretical basis for the HAND bacteria application in nitrogen removal from wastewaters containing heavy metals.
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Rapid and sensitive detection of the concentration of sialic acid (SA) in serum is crucial for early tumor screening and prognostic assessment; however, it still remains challenging. Here, we propose a novel kind of hydrogel grating sensor with boron affinity and molecular imprinting effects (B-MIP) for the rapid and sensitive detection of SA concentration in serum. The hydrogel gratings feature uniform surface relief microstructures and incorporate highly specific recognition binding sites into SA molecules provided by boron affinity and molecular imprinting. The periodic nanoridges of hydrogel gratings increase the specific surface area contacting the environmental solution; therefore, fast detection can be achieved within 2 min. Upon recognition of SA molecules, the height of hydrogel gratings changes at the nanoscale, causing a change in the diffraction efficiency of the hydrogel gratings. The B-MIP hydrogel grating sensors have highly specific binding sites to SA molecules distributed throughout the whole hydrogel and can preferentially and selectively recognize and respond to the SA molecules even in the presence of interference substances glucose and fructose with high concentrations. The B-MIP hydrogel grating sensors are effectively applicable for the rapid and sensitive detection of SA concentrations in real serum samples with satisfactory accuracy and precision. Our approach provides an excellent strategy to address the current challenges in SA detection and provides new insights into the detection of tumor markers in serum, thereby opening up new ways to accurately detect complex biological samples in analytical science.
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Biomarcadores Tumorais , Boro , Hidrogéis , Impressão Molecular , Ácido N-Acetilneuramínico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Humanos , Boro/química , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/análise , Hidrogéis/química , Técnicas BiossensoriaisRESUMO
Multiple types of omics data contain a wealth of biomedical information which reflect different aspects of clinical samples. Multi-omics integrated analysis is more likely to lead to more accurate clinical decisions. Existing cancer diagnostic methods based on multi-omics data integration mainly focus on the classification accuracy of the model, while neglecting the interpretability of the internal mechanism and the reliability of the results, which are crucial in specific domains such as precision medicine and the life sciences. To overcome this limitation, we propose a trustworthy multi-omics dynamic learning framework (TMODINET) for cancer diagnostic. The framework employs multi-omics adaptive dynamic learning to process each sample to provide patient-centered personality diagnosis by using self-attentional learning of features and modalities. To characterize the correlation between samples well, we introduce a graph dynamic learning method which can adaptively adjust the graph structure according to the specific classification results for specific graph convolutional networks (GCN) learning. Moreover, we utilize an uncertainty mechanism by employing Dirichlet distribution and Dempster-Shafer theory to obtain uncertainty and integrate multi-omics data at the decision level, ensuring trustworthy for cancer diagnosis. Extensive experiments on four real-world multimodal medical datasets are conducted. Compared to state-of-the-art methods, the superior performance and trustworthiness of our proposed algorithm are clearly validated. Our model has great potential for clinical diagnosis.
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The overactivated immune cells in the infectious lesion may lead to irreversible organ damages under severe infections. However, clinically used immunosuppressive anti-inflammatory drugs will usually disturb immune homeostasis and conversely increase the risk of infections. Regulating the balance between anti-inflammation and anti-infection is thus critical in treating certain infectious diseases. Herein, considering that hydrogen peroxide (H2O2), myeloperoxidase (MPO), and neutrophils are upregulated in the inflammatory microenvironment and closely related to the severity of appendectomy patients, an inflammatory-microenvironment-responsive nanomedicine is designed by using poly(lactic-co-glycolic) acid (PLGA) nanoparticles to load chlorine E6 (Ce6), a photosensitizer, and luminal (Lum), a chemiluminescent agent. The obtained Lum/Ce6@PLGA nanoparticles, being non-toxic within normal physiological environment, can generate cytotoxic single oxygen via bioluminescence resonance energy transfer (BRET) in the inflammatory microenvironment with upregulated H2O2 and MPO, simultaneously killing pathogens and excessive inflammatory immune cells in the lesion, without disturbing immune homeostasis. As evidenced in various clinically relevant bacterial infection models and virus-induced pneumonia, Lum/Ce6@PLGA nanoparticles appeared to be rather effective in controlling both infection and inflammation, resulting in significantly improved animal survival. Therefore, the BRET-based nanoparticles by simultaneously controlling infections and inflammation may be promising nano-therapeutics for treatment of severe infectious diseases.
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Inflamação , Nanomedicina , Nanopartículas , Animais , Nanomedicina/métodos , Nanopartículas/química , Inflamação/tratamento farmacológico , Camundongos , Modelos Animais de Doenças , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Clorofilídeos , Porfirinas/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Peróxido de Hidrogênio/metabolismoRESUMO
Aberrations in metabolism after intracerebral hemorrhage (ICH), particularly lactate metabolism, play a crucial role in the pathophysiology and patient outcome. To date, the evaluation of metabolism relies heavily on invasive methods such as microdialysis, restricting a comprehensive understanding of the metabolic mechanisms associated with ICH. This study proposes a noninvasive metabolic imaging method based on 2H magnetic resonance spectroscopy and imaging (2H-MRS/MRSI) to detect metabolic changes after ICH in vivo. To overcome the low-sensitivity limitation of 2H, we designed a new 1H-2H double-resonance coil with 2H-channel active detuning and proposed chemical shift imaging based on the balanced steady-state free precession method (CSI-bSSFP). Compared with the volume coil, the signal-to-noise ratio (SNR) of the new coil was increased by 4.5 times. In addition, the SNR of CSI-bSSFP was 1.5 times higher than that of conventional CSI. These two technologies were applied to measure lactate metabolic flux at different phases of ICH. The results show a higher lactate concentration in ICH rats than in control rats, which is in line with the increased expression of lactate dehydrogenase measured via immunohistochemistry staining (AUCLac_area/Glc_area: control, 0.08 ± 0.02 vs ICH-3d, 0.39 ± 0.05 vs ICH-7d, 0.18 ± 0.02, P < 0.01; H-score: control, 126.4 ± 5.03 vs ICH-3d, 168.4 ± 5.71 vs ICH-7d,133.6 ± 7.70, P < 0.05). A higher lactate signal also appeared near the ICH region than in normal brain tissue. In conclusion, 2H-MRS/MRSI shows potential as a useful method for in vivo metabolic imaging and noninvasive assessment of ICH.
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Hemorragia Cerebral , Deutério , Ácido Láctico , Ratos Sprague-Dawley , Animais , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/diagnóstico por imagem , Ratos , Ácido Láctico/metabolismo , Ácido Láctico/análise , Masculino , Deutério/química , Espectroscopia de Ressonância Magnética/métodos , Razão Sinal-Ruído , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagemRESUMO
The poor 5-year survival rate for bladder cancers is associated with the lack of efficient diagnostic and treatment techniques. Despite cystoscopy-assisted photomedicine and external radiation being promising modalities to supplement or replace surgery, they remain invasive or fail to provide real-time navigation. Here, we report non-invasive fractionated photodynamic therapy of bladder cancer with full-course real-time near-infrared-II imaging based on engineered X-ray-activated nanotransducers that contain lanthanide-doped nanoscintillators with concurrent emissions in visible and the second near-infrared regions and conjugated photosensitizers. Following intravesical instillation in mice with carcinogen-induced autochthonous bladder tumours, tumour-homing peptide-labelled nanotransducers realize enhanced tumour regression, robust recurrence inhibition, improved survival rates, and restored immune homeostasis under X-ray irradiation with accompanied near-infrared-II imaging. On-demand fractionated photodynamic therapy with customized doses is further achieved based on quantifiable near-infrared-II imaging signal-to-background ratios. Our study presents a promising non-invasive strategy to confront the current bladder cancer dilemma from diagnosis to treatment and prognosis.
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Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária , Animais , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Fotoquimioterapia/métodos , Camundongos , Fármacos Fotossensibilizantes/uso terapêutico , Raios X , Linhagem Celular Tumoral , Feminino , Humanos , Raios InfravermelhosRESUMO
BACKGROUND: Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ. METHODS: Western blot, immunohistochemical staining, and qRT-PCR assays were used to explore the mechanisms underlying TMZ promoting DKK1 expression and andrographolide (AND) inhibiting DKK1 expression. HPLC was used to detect the ability of andrographolide (AND) to penetrate the blood-brain barrier. MTT assay, bioluminescence images, magnetic resonance imaging (MRI) and H&E staining were employed to measure the proliferative activity of glioma cells and the growth of intracranial tumors. RESULTS: TMZ can promote DKK1 expression in glioma cells and brain tumors of an orthotopic model of glioma. DKK1 could promote glioma cell proliferation and tumor growth in an orthotopic model of glioma. Mechanistically, TMZ increased EGFR expression and subsequently induced the activation of its downstream MEK-ERK and PI3K-Akt pathways, thereby promoting DKK1 expression in glioma cells. Andrographolide inhibited TMZ-induced DKK1 expression through inactivating MEK-ERK and PI3K-Akt pathways. Andrographolide can cross the blood-brain barrier, the combination of TMZ and andrographolide not only improved the anti-tumor effects of TMZ but also showed a survival benefit in an orthotopic model of glioma. CONCLUSION: Andrographolide can enhance anti-tumor activity of TMZ against glioma by inhibiting DKK1 expression.
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Antineoplásicos Alquilantes , Neoplasias Encefálicas , Proliferação de Células , Diterpenos , Glioma , Peptídeos e Proteínas de Sinalização Intercelular , Temozolomida , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Temozolomida/farmacologia , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/genética , Glioma/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Humanos , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Camundongos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sinergismo Farmacológico , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: To evaluate the safety and efficacy of percutaneous biopsy and microwave ablation (B + MWA) in patients with pulmonary nodules (PNs) who are receiving antithrombotic therapy by rivaroxaban as bridging therapy. METHODS: The study comprised 187 patients with PNs who underwent 187 B + MWA sessions from January 1, 2020, to December 31, 2021. The enrolled patients were divided into two groups: Group A, who received antithrombotic therapy five days before the procedure and received rivaroxaban as a bridging drug during hospitalization, and group B, who had no antithrombotic treatment. Information about the technical success rate, positive biopsy rate, complete ablative rate, and major complications were collected and analyzed. RESULTS: Group A comprised 53 patients and group B comprised 134 patients. The technical success rate was 100% in both groups. The positive biopsy rates were 88.68% and 91.04%, respectively (p = 0.6211, X2 = 0.2443). In groups A and B, the complete ablative rates at 6, 12, and 24 months were 100.0% versus 99.25%, 96.23% versus 96.27%, and 88.68% versus 89.55%, respectively. There were no significant differences in bleeding and thrombotic complications between the two groups. No grade 5 complications occurred. CONCLUSIONS: It is generally considered safe and effective that patients who are on antithrombotic therapy by rivaroxaban as bridging to undergo B + MWA for treating PNs.
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Fibrinolíticos , Micro-Ondas , Rivaroxabana , Humanos , Rivaroxabana/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Micro-Ondas/uso terapêutico , Idoso , Fibrinolíticos/uso terapêutico , Nódulos Pulmonares Múltiplos/patologia , Nódulos Pulmonares Múltiplos/cirurgia , Biópsia/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Adulto , Ablação por Cateter/métodos , Estudos Retrospectivos , Inibidores do Fator Xa/uso terapêuticoRESUMO
Aluminum adjuvants remain the most commonly used vaccine adjuvants. Being rather effective in triggering humoral immunity, however, aluminum adjuvants usually show limited abilities in activating cellular immunities. Herein, by adding manganese ions during the preparation of aluminum adjuvant, a manganese-modified aluminum (Mn-Al) adjuvant is obtained, which can effectively stimulate both humoral and cellular immune responses. Such Mn-Al adjuvant can enhance antigen adsorption and promote antigen internalization by dendritic cells (DCs). Subsequently, the released Mn2+ can activate the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway to further promote DC activation. When combines with the model antigen ovalbumin (OVA), the Mn-Al-adjuvantes vaccine can induce high levels of antigen-specific antibody titers and high proportions of antigen-specific cytotoxic T cells in vivo. Moreover, the Mn-Al-adjuvanted vaccine elicited stronger antigen-specific humoral and cellular immune responses than high-dose of the aluminum-based adjuvant. Additionally, immunization of mice with OVA in the presence of the Mn-Al adjuvant significantly inhibited the growth of B16-OVA tumors. Furthermore, when formulated with human papillomavirus antigens, Mn-Al-adjuvanted vaccines show better in vivo vaccination performance than aluminum-adjuvanted vaccines. Therefore, the manganese-modified aluminum adjuvant may thus become a new vaccine adjuvant with the potential to replace conventional aluminum adjuvants.
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Gamma-delta (γδ) T cell-based cancer immunotherapies represent a promising avenue for cancer treatment. However, their development is challenged by the limited expansion and differentiation of the cells ex vivo. Here we induced the endogenous expansion and activation of γδ T cells through oral administration of garlic-derived nanoparticles (GNPs). We found that GNPs could significantly promote the proliferation and activation of endogenous γδ T cells in the intestine, leading to generation of large amount of interferon-γ (IFNγ). Moreover GNP-treated mice showed increased levels of chemokine CXCR3 in intestinal γδ T cells, which can drive their migration from the gut to the tumour environment. The translocation of γδ T cells and IFNγ from the intestine to extraintestinal subcutaneous tumours remodels the tumour immune microenvironment and synergizes with anti-PD-L1, inducing robust antitumour immunity. Our study delineates mechanistic insight into the complex gut-tumour interactome and provides an alternative approach for γδ T cell-based immunotherapy.
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Alho , Imunoterapia , Interferon gama , Nanopartículas , Microambiente Tumoral , Animais , Interferon gama/metabolismo , Nanopartículas/química , Alho/química , Camundongos , Administração Oral , Imunoterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Camundongos Endogâmicos C57BL , Receptores CXCR3/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linhagem Celular Tumoral , Feminino , Antígeno B7-H1/metabolismo , Intestinos/imunologia , Humanos , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Neoplasias/terapia , Neoplasias/imunologiaRESUMO
Autologous cancer vaccines represent a promising therapeutic approach against tumor relapse. Herein, a concise biomineralization strategy was developed to prepare an immunostimulatory autologous cancer vaccine through protein antigen-mediated growth of flower-like manganese phosphate (MnP) nanoparticles. In addition to inheriting the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING)-activating capacity of Mn2+, the resulting ovalbumin (OVA)-loaded MnP (OVA@MnP) nanoparticles with superior stability and pH-responsiveness enabled efficient priming of antigen-specific CD8+ T cell expansion through promoting the endo/lysosome escape and subsequent antigen cross-presentation of OVA. Resultantly, OVA@MnP vaccines upon subcutaneous vaccination elicited both prophylactic and therapeutic effects against OVA-expressing B16-F10 melanoma. Furthermore, the biomineralized autologous cancer vaccines prepared from the whole tumor cell lysates of the dissected tumors suppressed the growth of residual tumors, particularly in combination with anti-PD-1 immunotherapy. This study highlights a simple biomineralization approach for the controllable synthesis of cGAS-STING-activating autologous cancer vaccines to suppress postsurgical tumor relapse.
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A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.