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1.
J Agric Food Chem ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087686

RESUMO

As the demand for lactoferrin increases, the search for cost-effective alternative proteins becomes increasingly important. Attention naturally turns to other members of the transferrin family such as ovotransferrin. The iron-binding abilities of these proteins influence their characteristics, although the underlying mechanisms remain unclear. This overview systematically summarizes the effects of the iron-binding ability on the fate of food-derived transferrins (lactoferrin and ovotransferrin) and their potential applications. The findings indicate that iron-binding ability significantly influences the structure of food-derived transferrins, particularly their tertiary structure. Changes in structure influence their physicochemical properties, which, in turn, lead to different behaviors in response to environmental variations. Thus, these proteins exhibit distinct digestive characteristics by the time they reach the small intestine, ultimately performing varied physiological functions in vivo. Consequently, food-derived transferrins with different iron-binding states may find diverse applications. Understanding this capability is essential for developing food-derived transferrins and driving innovation in lactoferrin-related industries.

2.
Adv Sci (Weinh) ; : e2403158, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953329

RESUMO

In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO2 nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn2+-mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long-lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity.

3.
Mater Today Bio ; 26: 101095, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840796

RESUMO

Photothermal therapy (PTT) has garnered extensive attention as an efficient strategy for cancer therapy. Unfortunately, there are currently no suitable photothermal agents (PTAs) capable of effectively treating HER2-positive breast cancer (HER2+ BC) due to the challenges in addressing blood circulation and tumor accumulation. Here, we propose a HER2-specific macrophage biomimetic nanoplatform IR820@ZIF-8@EM (AMBP) for enhanced bio-photothermal therapy of HER2+ BC. An anti-HER2 antibody was expressed in engineered macrophages using the transmembrane expression technique. As an efficient PTAs, IR820 dyes were assembled into ZIF-8 as to develop a "nano-thermal-bomb". Homology modeling methods support that the expressed anti-HER2 antibody can specifically recognize the HER2 receptor. Moreover, antibody-dependent cell-mediated cytotoxicity can also be induced in HER2+ BC cells by AMBP. In vitro fluorescence confocal imaging showed that AMBP promoted the uptake of HER2+ cancer cells while in vivo anti-tumor experiments demonstrated that AMBP efficiently accumulates in the tumor regions. Finally, under spatiotemporally controlled near-infrared (NIR) irradiation, three of the six tumors were eradicated in AMBP-treated mice, demonstrating a safe and effective strategy. In conclusion, our research opens a new paradigm for antibody-specific macrophage, and it is expected that these characteristics will have substantial clinical translation potential for BC treatment.

4.
Nano Lett ; 24(20): 6131-6138, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38727077

RESUMO

Accurate intraoperative tumor delineation is critical to achieving successful surgical outcomes. However, conventional techniques typically suffer from poor specificity and low sensitivity and are time-consuming, which greatly affects intraoperative decision-making. Here, we report a cascade activatable near-infrared fluorescent (NIRF) probe IR780SS@CaP that can sequentially respond to tumor acidity and elevated glutathione levels for accurate intraoperative tumor localization. Compared with nonactivatable and single-factor activatable probes, IR780SS@CaP with a cascade strategy can minimize nonspecific activation and false positive signals in a complicated biological environment, affording a superior tumor-to-normal tissue ratio to facilitate the delineation of abdominal metastases. Small metastatic lesions that were less than 1 mm in diameter can be precisely identified by IR780SS@CaP and completely excised under NIRF imaging guidance. This study could benefit tumor diagnosis and image-guided tumor surgery by providing real-time information and reliable decision support, thus reducing the risk of both recurrence and complications to improve patient outcomes.


Assuntos
Corantes Fluorescentes , Corantes Fluorescentes/química , Humanos , Animais , Camundongos , Imagem Óptica/métodos , Linhagem Celular Tumoral , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Cirurgia Assistida por Computador/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos
5.
6.
JACS Au ; 4(4): 1345-1355, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38665667

RESUMO

A major limitation of tumor antiangiogenic therapy is the pronounced off-target effect, which can lead to unavoidable injury in multiple organs. Ensuring sufficient delivery and controlled release of these antiangiogenic agents at tumor sites is crucial for realizing their clinical application. Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

7.
ACS Nano ; 18(13): 9431-9442, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38507745

RESUMO

The simultaneous pursuit of accelerative radiative and restricted nonradiative decay is of tremendous significance to construct high-luminescence-efficiency fluorophores in the second near-infrared wavelength window (NIR-II), which is seriously hindered by the energy gap laws. Herein, a mash-up strategy of π-extension and deuteration is proposed to efficaciously ameliorate the knotty problem. By extending the π-conjugation of the aromatic fragment and introducing an isotope effect to the aggregation-induced emission luminogen (AIEgen), an improved oscillator strength (f), coupled with suppressed deformation and high-frequency oscillation in the excited state, are successively implemented. In this case, a faster rate of radiative decay (kr) and restricted nonradiative decay (knr) are simultaneously achieved. Moreover, the preeminent emissive property of AIEgen in the molecular state could be commendably inherited by the aggregates. The corresponding NIR-II emissive AIEgen-based nanoparticles display high brightness, large Stokes shift, and superior photostability simultaneously, which can be applied for image-guided cancer and sentinel lymph node (SLN) surgery. This work thus provides a rational roadmap to improve the luminescence efficiency of NIR-II fluorophores for biomedical applications.


Assuntos
Nanopartículas , Neoplasias , Cirurgia Assistida por Computador , Humanos , Luminescência , Neoplasias/patologia , Nanopartículas/química
8.
Acc Chem Res ; 57(6): 905-918, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38417027

RESUMO

Cancer vaccines have shown tremendous potential in preventing and treating cancer by providing immunogenic antigens to initiate specific tumor immune responses. An in situ vaccine prepared from an autologous tumor can mobilize a patient's own tumor cell lysate as a reservoir of specific antigens, thus triggering a broad immune response and diverse antitumor immunity in an individually tailored manner. Its efficacy is much better than that of conventional vaccines with a limited number of epitopes. Several conventional therapies, including radiotherapy (RT), chemotherapeutics, photodynamic therapy (PDT), and photothermal therapy (PTT) can activate an anticancer in situ vaccine response by inducing immunogenic cell death (ICD), triggering the exposure of tumor-associated antigens (TAAs), cancerous testis antigens, neoantigens, and danger-associated molecular patterns (DAMPs) with low cost. However, the immunogenicity of dying tumor cells is low, making released antigens and DAMPs insufficient to initiate a robust immune response against malignant cancer. Moreover, the immunosuppressive tumor microenvironment (TME) severely hinders the infiltration and sensitization of effector immune cells, causing tolerogenic immunological effects.Herein, we mainly focus on the research in developing nanoplatforms to surmount the major challenges met by ICD-based in situ vaccines. We first summarized a variety of nanotechnologies that enable enhanced immunogenicity of dying cancer cells by enhancing antigenicity and adjuvanticity. The robust antigenicity was obtained via regulating the tumor cells death mode or the dying state to amplify the recognition of tumor debris by professional antigen-presenting cells (APCs). The adjuvanticity was potentiated by raising the level or intensifying the activity of endogenous adjuvants or promoting the intelligent delivery of exogenous immunostimulants to activate immune cell recruitment and promote antigen presentation. Additionally, versatile approaches to reverse immunosuppressive TME to boost the in situ tumor vaccination response are also highlighted in detail. On one hand, by modulating the cell metabolism in TME, the expansion and activity of effector versus immunosuppressive cells can be optimized to improve the efficiency of in situ vaccines. On the other hand, regulating cellular components in TME, such as reversing adverse immune cell phenotypes or inhibiting the activity of interstitial cells, can also significantly enhance the ICD-based antitumor immunotherapy effect. Finally, our viewpoint on the future challenges and opportunities in this hopeful area is presented. We expect that this Account can offer much more insight into the design, planning, and development of cutting-edge in situ tumor vaccine platforms, promoting more attention and academic-industry collaborations, accelerating the advanced progress of in situ tumor vaccine-based immunotherapy in the clinic.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Vacinas Anticâncer/uso terapêutico , Nanomedicina , Morte Celular Imunogênica , Neoplasias/terapia , Vacinação , Adjuvantes Imunológicos , Microambiente Tumoral
9.
J Control Release ; 367: 697-707, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331001

RESUMO

Precise targeting is a major prerequisite for effective cancer therapy because it ensures a sufficient therapeutic dosage in tumors while minimizing off-target side effects. Herein, we report a live-macrophage-based therapeutic system for high-efficiency tumor therapy. As a proof of concept, anti-human epidermal growth factor receptor-2 (HER2) affibodies were genetically engineered onto the extracellular membrane of macrophages (AE-Mφ), which further internalized doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) nanoparticles (NPs) to produce a macrophage-based therapeutic system armed with anti-HER2 affibodies. NPs(DOX)@AE-Mφ were able to target HER2+ cancer cells and specifically elicit affibody-mediated cell therapy. Most importantly, the superior HER2 + -targeting capability of NPs(DOX)@AE-Mφ greatly guaranteed high accumulation at the tumor site for improved chemotherapy, which acted synergistically with cell therapy to significantly enhance anti-tumor efficacy. This study suggests that NPs(DOX)@AE-Mφ could be utilized as an innovative 'living targeted drug' platform for combining both macrophage-mediated cell therapy and targeted chemotherapy for the individualized treatment of solid tumors.


Assuntos
Nanopartículas , Neoplasias , Humanos , Portadores de Fármacos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Doxorrubicina/uso terapêutico , Macrófagos , Linhagem Celular Tumoral
10.
Nat Nanotechnol ; 19(1): 124-130, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37696994

RESUMO

In vivo quantitative assessment of oxyhaemoglobin saturation (sO2) status in tumour-associated vessels could provide insights into cancer metabolism and behaviour. Here we develop a non-invasive in vivo sO2 imaging technique to visualize the sO2 levels of healthy and tumour tissue based on photoluminescence bioimaging in the near-infrared IIb (NIR-IIb; 1,500-1,700 nm) window. Real-time dynamic sO2 imaging with a high frame rate (33 Hz) reveals the cerebral arteries and veins through intact mouse scalp/skull, and this imaging is consistent with the haemodynamic analysis results. Utilizing our non-invasive sO2 imaging, the tumour-associated-vessel sO2 levels of various cancer models are evaluated. A positive correlation between the tumour-associated-vessel sO2 levels and the basal oxygen consumption rate of corresponding cancer cells at the early stages of tumorigenesis suggests that cancer cells modulate the tumour metabolic microenvironment. We also find that a positive therapeutic response to the checkpoint blockade cancer immunotherapy could lead to a dramatic decrease of the tumour-associated-vessel sO2 levels. Two-plex dynamic NIR-IIb imaging can be used to simultaneously observe tumour-vessel sO2 and PD-L1, allowing a more accurate prediction of immunotherapy response.


Assuntos
Neoplasias , Oxiemoglobinas , Animais , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Diagnóstico por Imagem , Imunoterapia , Microambiente Tumoral
11.
Anim Biosci ; 37(3): 437-450, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37946431

RESUMO

OBJECTIVE: Vanin-1 (VNN1) is a pantetheinase that catalyses the hydrolysis of pantetheine to produce pantothenic acid and cysteamine. Our previous studies have shown that the VNN1 is specifically expressed in chicken liver which negatively regulated by microRNA-122. However, the functions of the VNN1 in lipid metabolism in chicken liver haven't been elucidated. METHODS: First, we detected the VNN1 mRNA expression in 4-week chickens which were fasted 24 hours. Next, knocked out VNN1 via CRISPR/Cas9 system in the chicken Leghorn Male Hepatoma cell line. Detected the lipid deposition via oil red staining and analysis the content of triglycerides (TG), low-density lipoprotein-C (LDL-C), and highdensity lipoprotein-C (HDL-C) after VNN1 knockout in Leghorn Male Hepatoma cell line. Then we captured various differentially expressed genes (DEGs) between VNN1-modified LMH cells and original LMH cells by RNA-seq. RESULTS: Firstly, fasting-induced expression of VNN1. Meanwhile, we successfully used the CRISPR/Cas9 system to achieve targeted mutations of the VNN1 in the chicken LMH cell line. Moreover, the expression level of VNN1 mRNA in LMH-KO-VNN1 cells decreased compared with that in the wild-type LMH cells (p<0.0001). Compared with control, lipid deposition was decreased after knockout VNN1 via oil red staining, meanwhile, the contents of TG and LDL-C were significantly reduced, and the content of HDL-C was increased in LMH-KO-VNN1 cells. Transcriptome sequencing showed that there were 1,335 DEGs between LMH-KO-VNN1 cells and original LMH cells. Of these DEGs, 431 were upregulated, and 904 were downregulated. Gene ontology analyses of all DEGs showed that the lipid metabolism-related pathways, such as fatty acid biosynthesis and long-chain fatty acid biosynthesis, were enriched. KEGG pathway analyses showed that "lipid metabolism pathway", "energy metabolism", and "carbohydrate metabolism" were enriched. A total of 76 DEGs were involved in these pathways, of which 29 genes were upregulated (such as cytochrome P450 family 7 subfamily A member 1, ELOVL fatty acid elongase 2, and apolipoprotein A4) and 47 genes were downregulated (such as phosphoenolpyruvate carboxykinase 1) by VNN1 knockout in the LMH cells. CONCLUSION: These results suggest that VNN1 plays an important role in coordinating lipid metabolism in the chicken liver.

12.
Adv Sci (Weinh) ; 11(10): e2305600, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38152963

RESUMO

Despite the potential of protein therapeutics, the cytosolic delivery of proteins with high efficiency and bioactivity remains a significant challenge owing to exocytosis and lysosomal degradation after endocytosis. Therefore, it is important to develop a safe and efficient strategy to bypass endocytosis. Inspired by the extraordinary capability of filamentous-actin (F-actin) to promote cell membrane fusion, a cyanine dye assembly-containing nanoplatform mimicking the structure of natural F-actin is developed. The nanoplatform exhibits fast membrane fusion to cell membrane mimics and thus enters live cells through membrane fusion and bypasses endocytosis. Moreover, it is found to efficiently deliver protein cargos into live cells and quickly release them into the cytosol, leading to high protein cargo transfection efficiency and bioactivity. The nanoplatform also results in the superior inhibition of tumor cells when loaded with anti-tumor proteins. These results demonstrate that this fusogenic nanoplatform can be valuable for cytosolic protein delivery and tumor treatment.


Assuntos
Actinas , Neoplasias , Humanos , Actinas/metabolismo , Citosol/metabolismo , Membrana Celular/metabolismo , Neoplasias/metabolismo
13.
Angew Chem Int Ed Engl ; 62(48): e202313420, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-37779105

RESUMO

An accurate detection of lung metastasis is of great significance for making better treatment choices and improving cancer prognosis, but remains a big challenge in clinical practice. In this study, we propose a reinventing strategy to develop a pH-activatable near-infrared (NIR) fluorescent nanoprobe, pulmonary metastasis tracer (denoted as PMT), based on assembly of NIR dye IR780 and calcium phosphate (CaP). By delicately tuning the intermolecular interactions during the assembly process and dye doping content, as well as the synthetic condition of probe, the fluorescence of PMT could be finely adjusted via the tumor acidity-triggered disassembly. Notably, the selected PMT9 could sharply convert subtle pH variations into a distinct fluorescence signal to generate high fluorescence ON/OFF contrast, dramatically reducing the background signals. Benefiting from such preferable features, PMT9 is able to precisely identify not only the tumor sites in orthotopic lung cancer models but also the pulmonary metastases in mice with remarkable signal-to-background ratio (SBR). This study provides a unique strategy to turn shortcomings of traditional dye IR780 during in vivo imaging into advantages and further expand the application of fluorescent probe to image lung associated tumor lesions.


Assuntos
Corantes Fluorescentes , Neoplasias Pulmonares , Animais , Camundongos , Corantes Fluorescentes/química , Diagnóstico por Imagem , Neoplasias Pulmonares/diagnóstico por imagem , Fluorescência , Imagem Óptica/métodos
14.
J Nanobiotechnology ; 21(1): 265, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563614

RESUMO

BACKGROUND: Emerging ferroptosis-driven therapies based on nanotechnology function either by increasing intracellular iron level or suppressing glutathione peroxidase 4 (GPX4) activity. Nevertheless, the therapeutic strategy of simultaneous iron delivery and GPX4 inhibition remains challenging and has significant scope for improvement. Moreover, current nanomedicine studies mainly use disulfide-thiol exchange to deplete glutathione (GSH) for GPX4 inactivation, which is unsatisfactory because of the compensatory effect of continuous GSH synthesis. METHODS: In this study, we design a two-in-one ferroptosis-inducing nanoplatform using iron-based metal-organic framework (MOF) that combines iron supply and GPX4 deactivation by loading the small molecule buthionine sulfoxide amine (BSO) to block de novo GSH biosynthesis, which can achieve sustainable GSH elimination and dual ferroptosis amplification. A coated lipid bilayer (L) can increase the stability of the nanoparticles and a modified tumor-homing peptide comprising arginine-glycine-aspartic acid (RGD/R) can achieve tumor-specific therapies. Moreover, as a decrease in GSH can alleviate resistance of cancer cells to chemotherapy drugs, oxaliplatin (OXA) was also loaded to obtain BSO&OXA@MOF-LR for enhanced cancer chemo-ferrotherapy in vivo. RESULTS: BSO&OXA@MOF-LR shows a robust tumor suppression effect and significantly improved the survival rate in 4T1 tumor xenograft mice, indicating a combined effect of dual amplified ferroptosis and GSH elimination sensitized apoptosis. CONCLUSION: BSO&OXA@MOF-LR is proven to be an efficient ferroptosis/apoptosis hybrid anti-cancer agent. This study is of great significance for the clinical development of novel drugs based on ferroptosis and apoptosis for enhanced cancer chemo-ferrotherapy.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Humanos , Camundongos , Animais , Butionina Sulfoximina/farmacologia , Oxaliplatina/farmacologia , Glutationa
15.
J Biophotonics ; 16(11): e202300066, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37556710

RESUMO

Intraoperative identification of malignancies using indocyanine green (ICG)-based fluorescence imaging could provide real-time guidance for surgeons. Existing ICG-based fluorescence imaging mostly operates in the near-infrared (NIR)-I (700-1000 nm) or the NIR-IIa' windows (1000-1300 nm), which is not optimal in terms of spatial resolution and contrast as their light scattering is higher than the NIR-IIb window (1500-1700 nm). It is highly desired to achieve ICG-based fluorescence imaging in the NIR-IIb window, but it is hindered by its ultra-low NIR-IIb emission tail of ICG. Herein, we employ a generative adversarial network to generate NIR-IIb ICG images directly from the acquired NIR-I ICG images. This approach was investigated by in vivo imaging of sub-surface vascular, intestine structure, and tumors, and their results demonstrated significant improvement in spatial resolution and contrast for ICG-based fluorescence imaging. It is potential for deep learning to improve ICG-based fluorescence imaging in clinical diagnostics and image-guided surgery in clinics.


Assuntos
Aprendizado Profundo , Verde de Indocianina , Verde de Indocianina/química , Imagem Óptica/métodos , Fluorescência
16.
J Food Sci Technol ; 60(6): 1793-1802, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37187988

RESUMO

The vegan food industry is gaining popularity nowadays. Ganoderma sp. is mainly used in the health and food industries as a medicinal, edible mushroom with high nutritional potential. Through two-stage cultivation methods, the study optimized the production of mycelial pellets for vegetarian food. When soybean powder was used as an alternative to egg yolk powder to meet vegetarian requirements, the number of pellets increased from 1100 to 1800 particles/dL, however, the pellet diameter reduced up to 22% (3.2-2.6 mm). The culture was expanded to the second stage using the Taguchi method coupled with Plackett-Burman Design and quantification by ImageJ software for enlarging pellets size. The optimal conditions were 10 mL of the first-stage broth inoculum, yeast powder (0.5 g/dL), glucose (0.5 g/dL), and MgSO4 (0.2 g/dL) at 100 rpm in the dark for 7 days. In 500 mL pilot scale production, the biomass yield was 0.31 g/dL and 3400 mycelium pellets/dL with a 5.2 mm diameter with appearance characteristics suitable for direct development as food. The study may help to develop a novel pellet food of filamentous fungi for the vegetarian market. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05719-x.

17.
Theranostics ; 13(5): 1571-1583, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056565

RESUMO

Rationale: Spatiotemporal control of pyroptosis has a profound impact on cancer immunotherapy. Owing to the precise spatiotemporal control and reduction in the side effects of ultrasound (US), sonodynamic therapy (SDT) is expected to be a promising mean to activate pyroptosis. Furthermore, the pyroptosis-initiated immune response can be amplified by enhanced lymphocyte infiltration occurring due to extracellular matrix (ECM) depletion. Therefore, it is highly desirable to develop a sonodynamic-immunomodulatory strategy to amplify pyroptosis-mediated tumor immunotherapy by remodeling of the tumor microenvironment, thereby enhancing tumor immunotherapy. Methods: We reported a potent strategy based on a sonosensitizer, which is composed of LY364947-loaded porous coordination network (PCN-224) camouflaged with a red blood cell (RBC) membrane and evaluated pyroptosis activation, collagen depletion, immunocyte infiltration, and adaptive immune response during the pyroptosis-initiated immune response in vitro and in vivo. Results: The sonosensitizer generated reactive oxygen species (ROS) under US irradiation and initiated the caspase-3 apoptotic signaling pathway, which is regarded as the key upstream activator of gasdermin E (GSDME)-mediated pyroptosis. During the subsequent anti-tumor immune response mediated by pyroptosis, LY364947 loosened the ECM structure via collagen depletion, resulting in enhanced T-lymphocyte infiltration and nearly complete eradication of tumors in a mouse model with the formation of immunological memory. Conclusion: Our findings indicate that sonodynamic-immunomodulatory pyroptotic strategy exhibits robust anti-tumor immune efficacy as well as provides novel insights into the role of pyroptosis in cancer immunology.


Assuntos
Piroptose , Microambiente Tumoral , Animais , Camundongos , Imunoterapia , Imunomodulação , Memória Imunológica , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio
18.
Medicine (Baltimore) ; 102(13): e33333, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37000085

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global public health event since 2019. Real-time reverse transcription polymerase chain reaction (RT-PCR) assays of upper respiratory tract specimens were used as the most common method for confirmation of SARS-CoV-2. Patients diagnosed with coronavirus disease 2019 and hospitalized in Cancer Center of Wuhan Union Hospital were retrospectively enrolled. Epidemiological, clinical, and laboratory records were analyzed with highlights on the pattern of results of repeated RT-PCR tests. Nine hundred eighty-four patients admitted to hospital between February 13, 2020 to March 10, 2020 were enrolled. The median age was 62.0 years (interquartile range 49.0-68.0) and 44.5% was male. Three thousand-three hundred eleven specimens were collected for RT-PCR tests with a median of 3 tests (interquartile range 2.0-4.0) per patient. Three hundred sixty-two (36.8%) patients showed positive records from repeated RT-PCR tests. For the 362 confirmed patients, 147 cases received further RT-PCR tests after 2 consecutive negative records of SARS-CoV-2 and 38 (26%) of them obtained a positive result. Ten (23%) of 43 patients showed positive results after 3 consecutive negative tests and 4 (24%) of 17 patients were positive after 4 negative tests. Consecutive negative RT-PCR tests with respiratory specimens could not guarantee a viral clearance.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos Retrospectivos , Nariz , Traqueia
20.
J Environ Sci (China) ; 124: 156-164, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182126

RESUMO

High phosphorus steel slag and carbonized rice husk are two common wastes characterized by high generation and low secondary use values. Through the reduction of high phosphorus steel slag by biomass, both wastes were fully utilized, thus reducing the negative impact on the environment. In this study, variables such as temperature, time, and amount of reactants were changed to determine the optimal conditions for the reaction of steel slag with carbonized rice husk at high temperatures. The actual amount of reducing agent consumed during the reduction was significantly greater than that predicted by theoretical calculations. Adding three carbon equivalent of carbonized rice husk and maintaining at 1500°C for 30 min could remove 79.25% of P2O5 in the slag. By modeling the material cycle in which high phosphorus steel slag was treated with biomass, the product could be used for crop growth. Meanwhile, the reduced iron and residual steel slag can be used to make steel again, thereby leading to a sharp reduction in fossil fuel usage and greenhouse gas emissions in this process.


Assuntos
Gases de Efeito Estufa , Oryza , Carbono , Combustíveis Fósseis , Resíduos Industriais , Ferro , Fósforo , Substâncias Redutoras , Aço
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