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1.
ACS Nano ; 18(11): 7923-7936, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38445625

RESUMO

Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Microfluídica , Imunoterapia , Neoplasias/terapia , Antígenos de Neoplasias
2.
J Genet Genomics ; 51(5): 479-491, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38218395

RESUMO

The human gut microbiome, a complex ecosystem, significantly influences host health, impacting crucial aspects such as metabolism and immunity. To enhance our comprehension and control of the molecular mechanisms orchestrating the intricate interplay between gut commensal bacteria and human health, the exploration of genome engineering for gut microbes is a promising frontier. Nevertheless, the complexities and diversities inherent in the gut microbiome pose substantial challenges to the development of effective genome engineering tools for human gut microbes. In this comprehensive review, we provide an overview of the current progress and challenges in genome engineering of human gut commensal bacteria, whether executed in vitro or in situ. A specific focus is directed towards the advancements and prospects in cargo DNA delivery and high-throughput techniques. Additionally, we elucidate the immense potential of genome engineering methods to enhance our understanding of the human gut microbiome and engineer the microorganisms to enhance human health.


Assuntos
Microbioma Gastrointestinal , Engenharia Genética , Humanos , Microbioma Gastrointestinal/genética , Engenharia Genética/métodos , Bactérias/genética , Genoma Bacteriano/genética
3.
Front Cell Dev Biol ; 11: 971091, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910156

RESUMO

Lipid metabolism disorder is the basis of atherosclerotic lesions, in which cholesterol and low-density lipoprotein (LDL) is the main factor involved with the atherosclerotic development. A high-fat and high-cholesterol diet can lead to this disorder in the human body, thus accelerating the process of disease. The development of single-cell RNA sequencing in recent years has opened the possibility to unbiasedly map cellular heterogeneity with high throughput and high resolution; alterations mediated by a high-fat and high-cholesterol diet at the single-cell transcriptomic level can be explored with this mean afterward. We assessed the aortic arch of 16-week old Apoe-/- mice of two control groups (12 weeks of chow diet) and two HFD groups (12 weeks of high fat, high cholesterol diet) to process single-cell suspension and use single-cell RNA sequencing to anatomize the transcripts of 5,416 cells from the control group and 2,739 from the HFD group. Through unsupervised clustering, 14 cell types were divided and defined. Among these cells, the cellular heterogeneity exhibited in endothelial cells and immune cells is the most prominent. Subsequent screening delineated ten endothelial cell subsets with various function based on gene expression profiling. The distribution of endothelial cells and immune cells differs significantly between the control group versus the HFD one. The existence of pathways that inhibit atherosclerosis was found in both dysfunctional endothelial cells and foam cells. Our data provide a comprehensive transcriptional landscape of aortic arch cells and unravel the cellular heterogeneity brought by a high-fat and high-cholesterol diet. All these findings open new perspectives at the transcriptomic level to studying the pathology of atherosclerosis.

4.
Biomaterials ; 291: 121871, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36323073

RESUMO

Effective activation of cGAS-STING pathway combined with immune checkpoint blockade (ICB) within the immunosuppressive tumor microenvironment to induce stronger immune responsiveness yet remains challenging. CRISPR-Cas9 gene editing technology, which offers the benefits of permanence and irreversibility, could recognize the target genome sequence with sgRNA (Guide RNA) and guide the Cas9 protease to knock down the target gene. Herein, a nanoplatform (HMnMPH) for dual activation of cGAS-STING pathway in combination with CRISPR-Cas9 gene editing to silence programmed death ligand 1 (PD-L1) to trigger long-term immunotherapy was reported. The HMnMPH consists of hollow manganese dioxide (HMn) loaded with STING agonist (MSA-2) and CRISPR-Cas9/sg-PD-L1 plasmid with further modification of hyaluronic acid (HA). In acidic and GSH overexpressed tumor environment, HMnPMH was degraded to release large amounts of Mn ions and STING agonists, strongly and persistently activating the cGAS-STING pathway to promote the release of type I interferon and pro-inflammatory factors. Meanwhile, the released CRISPR-Cas9 plasmid could knockdown the PD-L1 immune checkpoint and restart immunosuppressive T cells to differentiate into cytotoxic T lymphocytes significantly, which reduced the activity of primary and distal tumors and demonstrated a long-term immune memory effect on distal tumors.


Assuntos
Edição de Genes , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Sistemas CRISPR-Cas/genética , Imunoterapia , Neoplasias/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Microambiente Tumoral
5.
ACS Synth Biol ; 11(10): 3134-3153, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36094344

RESUMO

Intestinal probiotics are often used for the in situ treatment of diseases, such as metabolic disorders, tumors, and chronic inflammatory infections. Recently, there has been an increased emphasis on intelligent, customized treatments with a focus on long-term efficacy; however, traditional probiotic therapy has not kept up with this trend. The use of synthetic biology to construct gut-engineered probiotics as live therapeutics is a promising avenue in the treatment of specific diseases, such as phenylketonuria and inflammatory bowel disease. These studies generally involve a series of fundamental design issues: choosing an engineered chassis, improving the colonization ability of engineered probiotics, designing functional gene circuits, and ensuring the safety of engineered probiotics. In this review, we summarize the relevant past research, the progress of current research, and discuss the key issues that restrict the widespread application of intestinal engineered probiotic living therapeutics.


Assuntos
Doenças Inflamatórias Intestinais , Doenças Metabólicas , Probióticos , Humanos , Redes Reguladoras de Genes , Probióticos/uso terapêutico , Biologia Sintética
6.
ACS Omega ; 7(17): 15215-15222, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35572748

RESUMO

Cotton fiber (CF)-based electroconductive papers were prepared by facile aqueous dispersion and drying processes combined with carbon nanotubes (CNTs) or graphene nanosheets (GNPs). To enhance the electromagnetic interference (EMI) shielding performance of the manufactured nanocomposites, the electroconductive papers were soaked with epoxy resin, which cooperated with the inner sprayed Fe3O4 nanoparticles. The EMI shielding effectiveness of Epoxy/CF-30-Fe3O4-30GNPs reached 33.1 dB, of which over 85.0% is attributed to absorption, which is mainly believed to be caused by the combination of GNPs and Fe3O4 nanoparticles due to their special structures and synergetic effects. Moreover, the infiltration of epoxy between the randomly distributed loose CFs and the multiple reflections inside the interconnected networks could also help to improve the EMI shielding performance of GNP-added samples. The prepared lightweight and stiff Epoxy/CF-30-Fe3O4-30GNP composites have promising applications in civil or military fields.

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