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Journal of Ethnopharmacology Jun 2024The traditional medicinal formulation, Qifu-yin (QFY), has been widely prescribed for Alzheimer's disease (AD) treatment in China, yet the comprehensive mechanisms...
ETHNOPHARMACOLOGICAL RELEVANCE
The traditional medicinal formulation, Qifu-yin (QFY), has been widely prescribed for Alzheimer's disease (AD) treatment in China, yet the comprehensive mechanisms through which QFY mitigates AD pathology remain to be fully delineated.
AIM OF THE STUDY
This study aimed to explore the therapeutic implications of QFY on the synaptic injury and oxidative stress in the hippocampus of APPswe/PS1dE9 (APP/PS1) mice, with a concerted effort to elucidate the molecular mechanisms related to synaptic preservation and memory improvement.
MATERIALS AND METHODS
The components of QFY were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The neuroprotective effects of QFY was evaluated using six-month-old male APP/PS1 mice. Subsequent to a 15 days of QFY regimen, spatial memory was assessed utilizing the Morris water maze (MWM) test. Amyloid-beta (Aβ) aggregation was detected via immunostaining, while the quantification of Aβ and Aβ was achieved through enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to investigate the synaptic structure and mitochondrial morphology. Golgi staining was applied to examine dendritic spine density. Reactive oxygen species (ROS), 3-nitrotyrosine (3-NT) and 4-hydroxy-nonenal (4-HNE) assays were employed to assess oxidative stress. The expression profiles of Aβ metabolism-associated enzymes and the Keap1/Nrf2/ARE signaling pathway were determined by Western blot.
RESULTS
A total of 20 principal compounds in QFY were identified. QFY mitigated memory deficits of APP/PS1 mice, including reducing escape latency and search distance and increasing the time and distance spent in the target quadrant. In addition, QFY increased platform crossings of APP/PS1 mice in the probe trial of MWM tests. TEM analysis showed that QFY increased synapse number in the CA1 region of APP/PS1 mice. Further studies indicated that QFY elevated the expression levels of Post synaptic density protein 95 (PSD95) and synaptophysin, and mitigated the loss of dendritic spine density in the hippocampus of APP/PS1 mice. QFY has been shown to ameliorated the structural abnormalities of mitochondria, including mitochondrial dissolution and degradation, up-regulate ATP synthesis and membrane potential in the hippocampus of APP/PS1 mice. Moreover, QFY activated the Keap1/Nrf2/ARE signaling pathway in the hippocampus of APP/PS1 mice, which might contribute to the neuroprotective effects of QFY.
CONCLUSION
QFY activates the Keap1/Nrf2/ARE signaling, and protects against synaptic and mitochondrial dysfunction in APP/PS1 mice, proposing a potential alternative therapeutic strategy for AD management.
PubMed: 38942156
DOI: 10.1016/j.jep.2024.118497 -
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 2024Self-assembly of nanoclusters (NCs) is an effective synthetic method for preparing functionalized nanomaterials. However, the assembly process and mechanisms in...
Self-assembly of nanoclusters (NCs) is an effective synthetic method for preparing functionalized nanomaterials. However, the assembly process and mechanisms in solutions still remain ambiguous owing to the limited strategies to monitor intermediate assembled states. Herein, the self-assembly process of amphiphilic molecule 4POSS-DL-POM (consisting of four polyhedral oligomeric silsesquioxanes, a dendritic linker, and one polyoxometalate) by evaporation of acetone in a mixed acetone/n-decane solution is monitored by time-resolved synchrotron small-angle X-ray scattering (SAXS). Scattering data assessments, including Kratky analysis, pair distance distribution function, and model fitting, track the self-assembly process of 4POSS-DL-POM from a fractal network to compact NCs, then to core-shell NCs, and finally to superlattice structure. The calculated average aggregation number of a core-shell NC is 11 according to the parameters obtained from core-shell model fitting, in agreement with electron microscopy. The fundamental understanding of the self-assembly dynamics from heterocluster into NCs provides principles to control building block shape and guide target aggregation, which can further promote the design and construction of highly ordered cluster-assembled functional nanomaterials.
PubMed: 38941936
DOI: 10.1016/j.jcis.2024.06.156 -
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 -
Medicine Jun 2024Abdominal aortic aneurysm (AAA) is a cardiovascular disease that seriously threatens human health and brings huge economic burden. At present, its pathogenesis remains...
Abdominal aortic aneurysm (AAA) is a cardiovascular disease that seriously threatens human health and brings huge economic burden. At present, its pathogenesis remains unclear and its treatment is limited to surgical treatment. With the deepening and analysis of studies on the mechanism of ferroptosis, a new idea has been provided for the clinical management of AAA patients, including diagnosis, treatment and prevention. Therefore, this paper aims to construct a competitive endogenous RNA (ceRNA) regulatory axis based on ferroptosis to preliminarily explore the pathogenesis and potential therapeutic targets of AAA. We obtained upregulated and downregulated ferroptosis-related DEGs (FRGs) from GSE144431 dataset and 60 known ferroptosis-related genes. Pearson correlation analysis was used to find aldoketone reductase 1C (AKR1C1) in AAA samples. Enrichment analysis of these genes was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Correlation test between immune cells and AKR1C1 was investigated through single-sample gene set enrichment analysis (ssGSEA). The AKR1C1-miRNA pairs were predicted by the TargetScan database and miRWalk database. Circular RNA (CircRNA)-miRNA pairs were selected by the CircInteractome database. Overlapping miRNA between circRNA-miRNA and AKR1C1-miRNA pairs was visualized by Venn diagram. Finally, the circRNA-miRNA-mRNA axis was constructed by searching for upstream circRNA and downstream mRNA of overlapping miRNA. Only one downregulated AKR1C1 gene was found in GSE144431 and 60 ferroptosis-related genes. Functional Enrichment and Pathway Analysis of AKR1C1-related genes were further explored, and it was observed that they were mainly enriched in "response to oxidative stress," "glutathione biosynthetic process" and "nonribosomal peptide biosynthetic process," "Ferroptosis," "Glutathione metabolism" and "Chemical carcinogenesis-reactive oxygen species." They were also found to be significantly associated with most immune cells, including Activated Dendritic cells, CD56dim Natural killer cells, Gamma Delta T cells, Immature B cells, Plasmacytoid dendritic cell, Type 2 T helper cell, Activated CD4 T cell and Type 1 T helper cell. Has_circ_0005073-miRNA-543 and AKR1C1-miRNA-543 were identified by Online Database analysis. Therefore, we have established the has_circ_0005073/miRNA-543/AKR1C1 axis in AAA. We found AKR1C1 was differentially expressed between normal and AAA groups. Based on AKR1C1, we constructed the has_circ_0005073/miRNA-543/AKR1C1 axis to analyze AAA.
Topics: Humans; Aortic Aneurysm, Abdominal; Ferroptosis; MicroRNAs; 20-Hydroxysteroid Dehydrogenases; RNA, Messenger; RNA, Circular; Down-Regulation
PubMed: 38941402
DOI: 10.1097/MD.0000000000038749 -
Investigational New Drugs Jun 2024The present study aimed to clarify the hypothesis that auger emitter I particles in combination with PARP inhibitor Olaparib could inhibit pancreatic cancer progression...
The present study aimed to clarify the hypothesis that auger emitter I particles in combination with PARP inhibitor Olaparib could inhibit pancreatic cancer progression by promoting antitumor immune response. Pancreatic cancer cell line (Panc02) and mice subcutaneously inoculated with Panc02 cells were employed for the in vitro and in vivo experiments, respectively, followed by I and Olaparib administrations. The apoptosis and CRT exposure of Panc02 cells were detected using flow cytometry assay. QRT-PCR, immunofluorescence, immunohistochemical analysis, and western blot were employed to examine mRNA and protein expression. Experimental results showed that I combined with Olaparib induced immunogenic cell death and affected antigen presentation in pancreatic cancer. I in combination with Olaparib influenced T cells and dendritic cells by up-regulating CD4, CD8, CD69, Caspase3, CD86, granzyme B, CD80, and type I interferon (IFN)-γ and down-regulating Ki67 in vivo. The combination also activated the cyclic GMP-AMP synthase stimulator of IFN genes (Sting) pathway in Panc02 cells. Moreover, Sting knockdown alleviated the effect of the combination of I and Olaparib on pancreatic cancer progression. In summary, I in combination with Olaparib inhibited pancreatic cancer progression through promoting antitumor immune responses, which may provide a potential treatment for pancreatic cancer.
PubMed: 38941055
DOI: 10.1007/s10637-024-01454-y