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Computer Methods in Biomechanics and... Jun 2024The effective reconstruction of osteochondral biomimetic structures is a key factor in guiding the regeneration of full-thickness osteochondral defects. Due to the...
The effective reconstruction of osteochondral biomimetic structures is a key factor in guiding the regeneration of full-thickness osteochondral defects. Due to the avascular nature of hyaline cartilage, the greatest challenge in constructing this scaffold lies in both utilizing the biomimetic structure to promote vascular differentiation for nutrient delivery to hyaline cartilage, thereby enhancing the efficiency of osteochondral reconstruction, and effectively blocking vascular ingrowth into the cartilage layer to prevent cartilage mineralization. However, the intrinsic relationship between the planning of the microporous pipe network and the flow resistance in the biomimetic structure, and the mechanism of promoting cell adhesion to achieve vascular differentiation and inhibiting cell adhesion to block the growth of blood vessels are still unclear. Inspired by the structure of tree trunks, this study designed a biomimetic tree-like tubular network structure for osteochondral scaffolds based on Murray's law. Utilizing computational fluid dynamics, the study investigated the influence of the branching angle of micro-pores on the flow velocity, pressure distribution, and scaffold permeability within the scaffold. The results indicate that when the differentiation angle exceeds 50 degrees, the highest flow velocity occurs at the confluence of tributaries at the ninth fractal position, forming a barrier layer. This structure effectively guides vascular growth, enhances nutrient transport capacity, increases flow velocity to promote cell adhesion, and inhibits cell infiltration into the cartilage layer.
PubMed: 38943424
DOI: 10.1080/10255842.2024.2372612 -
Nature Immunology Jun 2024The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (T) cells are critical in helping B cells during germinal center...
The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (T) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and T cells was found within T cell zones of colonic lymphoid follicles. T cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted T cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, T cells transdifferentiated into long-lived pathogenic T1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of T cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.
PubMed: 38942990
DOI: 10.1038/s41590-024-01882-1 -
Nature Communications Jun 2024Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic...
Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy. Genetic and pharmacological studies demonstrate that PIKfyve ablation enhances the function of CD11c cells (predominantly dendritic cells) via selectively altering the non-canonical NF-κB pathway. Both loss of Pikfyve in CD11c cells and treatment with apilimod, a potent and specific PIKfyve inhibitor, restrained tumor growth, enhanced DC-dependent T cell immunity, and potentiated ICB efficacy in tumor-bearing mouse models. Furthermore, the combination of a vaccine adjuvant and apilimod reduced tumor progression in vivo. Thus, PIKfyve negatively regulates the function of CD11c cells, and PIKfyve inhibition has promise for cancer immunotherapy and vaccine treatment strategies.
Topics: Animals; Humans; Dendritic Cells; Mice; Phosphatidylinositol 3-Kinases; CD11c Antigen; Morpholines; Cell Line, Tumor; Immunotherapy; Neoplasms; Mice, Inbred C57BL; Female; Immune Checkpoint Inhibitors; NF-kappa B; T-Lymphocytes; Protein Kinase Inhibitors; Hydrazones; Pyrimidines
PubMed: 38942798
DOI: 10.1038/s41467-024-48931-9 -
International Journal of Pharmaceutics Jun 2024We have recently witnessed that considerable progresses have been made in the rapid detection and appropriate treatments of COVID-19, but still this virus remains one of...
We have recently witnessed that considerable progresses have been made in the rapid detection and appropriate treatments of COVID-19, but still this virus remains one of the main targets of world research. Based on the knowledge of the complex mechanism of viral infection we designed peptide-dendrimer inhibitors of SARS-CoV-2with the aim to block cell infection through interfering with the host-pathogen interactions. We used two different strategies: i) the first one aims at hindering the virus anchorage to the human cell; ii) the second -strategy points to interfere with the mechanism of virus-cell membrane fusion. We propose the use of different nanosized carriers, formed by several carbosilane dendritic wedges to deliver two different peptides designed to inhibit host interaction or virus entry. The antiviral activity of the peptide-dendrimers, as well as of free peptides and free dendrimers was evaluated through the use of SARS-CoV-2 pseudotyped lentivirus. The results obtained show that peptides designed to block host-pathogen interaction represent a valuable strategy for viral inhibition.
PubMed: 38942185
DOI: 10.1016/j.ijpharm.2024.124389 -
Journal of Controlled Release :... Jun 2024Tumor-associated macrophages (TAMs) constitute 50-80% of stromal cells in most solid tumors with high mortality and poor prognosis. Tumor-infiltrating dendritic cells...
Tumor-associated macrophages (TAMs) constitute 50-80% of stromal cells in most solid tumors with high mortality and poor prognosis. Tumor-infiltrating dendritic cells (TIDCs) and TAMs are key components mediating immune responses within the tumor microenvironment (TME). Considering their refractory properties, simultaneous remodeling of TAMs and TIDCs is a potential strategy of boosting tumor immunity and restoring immunosurveillance. In this study, mannose-decorated poly(lactic-co-glycolic acid) nanoparticles loading with R848 (Man-pD-PLGA-NP@R848) were prepared to dually target TAMs and TIDCs for efficient tumor immunotherapy. The three-dimensional (3D) cell culture model can simulate tumor growth as influenced by the TME and its 3D structural arrangement. Consequently, cancer spheroids enriched with tumor-associated macrophages (TAMs) were fabricated to assess the therapeutic effectiveness of Man-pD-PLGA-NP@R848. In the TME, Man-pD-PLGA-NP@R848 targeted both TAMs and TIDCs in a mannose receptor-mediated manner. Subsequently, Man-pD-PLGA-NP@R848 released R848 to activate Toll-like receptors 7 and 8, following dual-reprograming of TIDCs and TAMs. Man-pD-PLGA-NP@R848 could uniquely reprogram TAMs into antitumoral phenotypes, decrease angiogenesis, reprogram the immunosuppressive TME from "cold tumor" into "hot tumor", with high CD4+ and CD8+ T cell infiltration, and consequently hinder tumor development in B16F10 tumor-bearing mice. Therefore, dual-reprograming of TIDCs and TAMs with the Man-pD-PLGA-NP@R848 is a promising cancer immunotherapy strategy.
PubMed: 38942083
DOI: 10.1016/j.jconrel.2024.06.062 -
Klinische Monatsblatter Fur... Jun 2024
PubMed: 38942034
DOI: 10.1055/a-2350-1122 -
Klinische Monatsblatter Fur... Jun 2024Corneal nerves and dendritic cells are increasingly being visualised to serve as clinical parameters in the diagnosis of ocular surface diseases using intravital... (Review)
Review
Corneal nerves and dendritic cells are increasingly being visualised to serve as clinical parameters in the diagnosis of ocular surface diseases using intravital confocal microscopy. In this review, different methods of image analysis are presented. The use of deep learning algorithms, which enable automated pattern recognition, is explained in detail using our own developments and compared with other established methods.
Topics: Cornea; Dendritic Cells; Humans; Microscopy, Confocal; Ophthalmic Nerve; Deep Learning; Corneal Diseases; Pattern Recognition, Automated; Image Processing, Computer-Assisted; Intravital Microscopy; Algorithms
PubMed: 38941998
DOI: 10.1055/a-2307-0313 -
Journal of Colloid and Interface Science Jun 2024Aqueous zinc batteries (AZBs) with the advantages of safety, low cost, and sustainability are promising candidates for large-scale energy storage devices. However, the...
Aqueous zinc batteries (AZBs) with the advantages of safety, low cost, and sustainability are promising candidates for large-scale energy storage devices. However, the issues of interface side reactions and dendrite growth at the zinc metal anode (ZMA) significantly harm the cycling lifespan of AZBs. In this study, we designed a nano-molecular sieve additive, fullerenol (C(OH)), which possesses a surface rich in hydroxyl groups that can be uniformly dispersed in the aqueous solution, and captures free water in the electrolyte, thereby suppressing the occurrence of interfacial corrosion. Besides, fullerenol can be further reduced to fullerene (C) on the surface of ZMA, holding a unique self-smoothing effect that can inhibit the growth of dendritic Zn. With the synergistic action of these two effects, the fullerenol-contained electrolyte (FE) enables dendrite-free ZMAs. The Zn-Ti half-cell using FE exhibits stable cycling over 2500 times at 5 mA cm with an average Coulombic efficiency as high as 99.8 %. Additionally, the Zn-NaVO cell using this electrolyte displays a capacity retention rate of 100 % after 1000 cycles at -20 °C. This work provides important insights into the molecular design of multifunctional electrolyte additives.
PubMed: 38941928
DOI: 10.1016/j.jcis.2024.06.182 -
Biomedicine & Pharmacotherapy =... Jun 2024Vaccines are an effective intervention for preventing infectious diseases. Currently many vaccine strategies are designed to improve vaccine efficacy by controlling...
Vaccines are an effective intervention for preventing infectious diseases. Currently many vaccine strategies are designed to improve vaccine efficacy by controlling antigen release, typically involving various approaches at the injection site. Yet, strategies for intracellular slow-release of antigens in vaccines are still unexplored. Our study showed that controlling the degradation of antigens in dendritic cells and slowing their transport from early endosomes to lysosomes markedly enhances both antigen-specific T-cell immune responses and germinal center B cell responses. This leads to the establishment of sustained humoral and cellular immunity in vivo imaging and flow cytometry indicated this method not only prolongs antigen retention at the injection site but also enhances antigen concentration in lymph nodes, surpassing traditional Aluminium (Alum) adjuvants. Additionally, we demonstrated that the slow antigen degradation induces stronger follicular helper T cell responses and increases proportions of long-lived plasma cells and memory B cells. Overall, these findings propose that controlling the speed of antigens transport in dendritic cells can significantly boost vaccine efficacy, offering an innovative avenue for developing highly immunogenic next-generation vaccines.
PubMed: 38941888
DOI: 10.1016/j.biopha.2024.117036 -
Annual Review of Immunology Jun 2024Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic... (Review)
Review
Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and the ensuing production of type I interferon and other soluble mediators, which orchestrate innate and adaptive responses. We review several aspects of pDC biology that have recently come to the fore. We discuss emerging questions regarding the lineage affiliation and origin of pDCs and argue that these cells constitute an integral part of the dendritic cell lineage. We emphasize the specific function of pDCs as innate sentinels of virus infection, particularly their recognition of and distinct response to virus-infected cells. This essential evolutionary role of pDCs has been particularly important for the control of coronaviruses, as demonstrated by the recent COVID-19 pandemic. Finally, we highlight the key contribution of pDCs to systemic lupus erythematosus, in which therapeutic targeting of pDCs is currently underway.
Topics: Dendritic Cells; Humans; COVID-19; Animals; Immunity, Innate; SARS-CoV-2; Lupus Erythematosus, Systemic; Toll-Like Receptors; Cell Differentiation; Cell Lineage
PubMed: 38941603
DOI: 10.1146/annurev-immunol-090122-041105