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Noninvasive focused ultrasound non-specifically activating spleen immunological function to universally suppress tumor proliferation: a new strategy for cancer immunotherapy

ABSTRACT: Noninvasive focused ultrasound non-specifically activating spleen immunological function to universally suppress tumor proliferation: a new strategy for cancer immunotherapy

PROVIDER: PRJNA1110590 | ENA |

REPOSITORIES: ENA

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Noninvasive focused ultrasound non-specifically activating spleen immunological function to universally suppress tumor proliferation: a new strategy for cancer immunotherapy -NK cells

Project description:Noninvasive focused ultrasound non-specifically activating spleen immunological function to universally suppress tumor proliferation: a new strategy for cancer immunotherapy -NK cells

| PRJNA1111523 | ENA

Noninvasive focused ultrasound non-specifically activating spleen immunological function to universally suppress tumor proliferation: a new strategy for cancer immunotherapy

Project description:CD8 T cells were sorted from the spleen using the Beckman Kurt MoFlo Astrios ultra high speed flow cytometry sorting system. Subsequently, general transcriptome sequencing was performed when the positive cell rate was greater than 90% detected by flow cytometry. The cDNA library construction and sequencing of all RNA samples were performed by Shanghai Ouyi Biomedical Technology Co., LTD. Transcriptome sequencing was performed to screen differentially expressed genes (DEGs). Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to annotate the function of the DEGs. The results revealed that FUS firstly regulated calcium-related signaling pathways to further modulate other signaling pathways, such as ECM-receptor interaction, PI3K-AKT signaling pathway, Rap1 signaling pathway and Hippo signaling pathway to promote immune cell proliferation, migration and activation to suppress cancer cell deterioration.

2025-09-03 | GSE267237 | GEO

Noninvasive focused ultrasound non-specifically activating spleen immunological function to universally suppress tumor proliferation: a new strategy for cancer immunotherapy -NK cells

Project description:NK cells were sorted from the spleen using the Beckman Kurt MoFlo Astrios ultra high speed flow cytometry sorting system. Subsequently, general transcriptome sequencing was performed when the positive cell rate was greater than 90% detected by flow cytometry. The cDNA library construction and sequencing of all RNA samples were performed by Shanghai Ouyi Biomedical Technology Co., LTD. Transcriptome sequencing was performed to screen differentially expressed genes (DEGs). Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to annotate the function of the DEGs. The results revealed that FUS firstly regulated calcium-related signaling pathways to further modulate other signaling pathways, such as ECM-receptor interaction, PI3K-AKT signaling pathway, Rap1 signaling pathway and Hippo signaling pathway to promote immune cell proliferation, migration and activation to suppress cancer cell deterioration.

2025-09-03 | GSE267445 | GEO

Transcriptomic profiling of diabetic rats treated with peripherical focused ultrasound (pFUS)

Project description:Transcriptomic profiling of diabetic rats treated with peripherical focused ultrasound (pFUS)

| PRJNA808966 | ENA

Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation

Project description:Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects. To measure the spatiotemporal kinetics of local and abscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and Controltralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.

2023-01-12 | GSE221448 | GEO

Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound

Project description:Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise, and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (> 24 hours) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state. To investigate the mechanism of ultrasound-induced neuronal activation, we applied ultrasound stimulation in hypothalamic preoptic area region and performed single-nuclei RNA sequencing in the ultrasound stimulated neurons (US+) and neurons without ultrasound stimulation (US-). In our sn-RNAseq analysis, we examined the association between the expression of neuronal activation markers (or IEGs) and ion channels, as well as neuron types.

2023-03-29 | GSE228180 | GEO

Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

Project description:Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

| PRJNA816515 | ENA

Microarray analysis of rat hippocampal microvessels at acute time points following focused ultrasound-induced increase in blood-brain barrier permeability

Project description:Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Microvessels were collected by laser capture microdissection. Relative gene expression was compared between samples collected from the sonicated hemisphere and samples collected from the hemisphere contralateral to sonication, as well as samples collected from rats not undergoing the FUS procedure.

2017-09-01 | E-MTAB-5251 | biostudies-arrayexpress

Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically- and biochemically-driven responses to focused ultrasound blood-brain barrier disruption - additional non-FUS controls

Project description:Focused ultrasound (FUS) blood brain barrier disruption (BBBD) permits the noninvasive, targeted, and repeatable delivery of drugs to the brain. FUS BBBD also elicits secondary responses capable of augmenting immunotherapies, clearing amyloid-β and hyperphosphorylated tau, and driving neurogenesis. Leveraging these secondary effects will benefit from an understanding of how they correlate to the magnitude of FUS BBBD and are differentially affected by the mechanical and biochemical stimuli imparted during FUS BBBD. Microbubble activation (MBA) and contrast enhancement (CE) differentially predicted expression of 1,124 genes 6 h or 24 h later. While there existed overlap in the transcripts correlated with MBA vs CE, MBA was principally predictive of expression of genes associated with endothelial reactivity while CE chiefly predicted sterile inflammation gene sets. Over-representation analysis identified transcripts not previously linked to BBBD, including actin filament organization, which is likely important for BBB recovery. Transcripts and pathways associated with neurogenesis, microglial activation, and amyloid-β clearance were significantly correlated to BBBD metrics. This submission includes non-FUS controls to supplement other studies analyzed within the work (GSE152171, GSE141728).

2021-09-27 | GSE184751 | GEO

Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

Project description:Focused Ultrasound (FUS) combined with microbubbles (FUS+MB) to transiently open the blood brain barrier (BBB) has shown promise as an immunotherapeutic in models of neurodegenerative disorders - resulting in significantly reduced pathological load and improved cognition. Preliminary histology and bulk tissue analysis of FUS+MB have indicated brain macrophage changes as a potential mechanism of the immunotherapy. However, prior to this study the temporal effect of FUS+MB on the two dominant brain macrophage populations - microglia and central nervous system associated macrophages (CAM) has not been reported. In this study, we establish that FUS+MB triggers a biphasic process involving both microglia and CAM. In the Phase I, 24h after treatment, microglia and resident CAM exhibit an early response signature, characterized by the upregulation of recruitment-associated chemokine and cytokines. In Phase II, 72h after treatment, CAM population size increases dramatically and both cell types exhibit a late response signature, characterized by upregulation of interferon genes indicative of cellular activation and immune response. Next, cell cycle analysis and immunohistochemistry indicate that microglia exhibit increased proliferation across both phases but CAM do not. Finally, the brain macrophage population size is correlated with the ultrasound-induced cavitation dose, indicating a dose-dependent response to treatment. The findings presented herein not only provide insight into the mechanism of the FUS+MB immunomodulatory effects but also into a mechanism of brain macrophage response that is capable of ameliorating neurological disease.

2023-06-17 | GSE198707 | GEO

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