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Intranasal administration of a multiplex targeting SCLMs@FEN1-hpDNAs with synergistic baicalein for pulmonary anti-viral treatment

ABSTRACT: Intranasal administration of a multiplex targeting SCLMs@FEN1-hpDNAs with synergistic baicalein for pulmonary anti-viral treatment

PROVIDER: PRJNA1199957 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31758646_1.fastq.gz	Fastqsanger.gz
	SRR31758646_2.fastq.gz	Fastqsanger.gz
	SRR31758647_1.fastq.gz	Fastqsanger.gz
	SRR31758647_2.fastq.gz	Fastqsanger.gz
	SRR31758648_1.fastq.gz	Fastqsanger.gz

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Intranasal administration of a multiplex targeting SCLMs@FEN1-hpDNAs with synergistic baicalein for pulmonary anti-viral treatment

Project description:Here we reported an anti-viral strategy for SARS-CoV-2 infection: intranasal administration of silica cross-linked micelles (SCLMs) encapsulating in vitro purified NES-FEN1-NES protein and a set of hpDNAs (shorted as SCLMs@FEN1-hpDNAs). The set of hpDNAs multiplex targeted SARS-CoV-2’s N gene RNA and the host Ctsl gene mRNA. In vitro experiments demonstrated the purified NES-FEN1-NES protein transfected into cells has efficient mRNA knockdown ability when guided by hpDNAs. The intranasal administration of SCLMs exhibited high pulmonary accessibility, and SCLMs@FEN1-hpDNAs effectively downregulated targeted gene expression in vivo. The efficacy is enhanced by synergistic intranasal baicalein by improving cellular uptake and anti-inflammatory effects. In a mouse model of SARS-CoV-2 infection, the combination with baicalein and SCLMs@FEN1-hpDNAs inhibited the virus replication, improved survival rates, and reduced neuroinflammation. This study highlights the potential of intranasal SCLMs@FEN1-hpDNAs with baicalein as a promising approach for treating respiratory diseases.

2024-12-19 | GSE284624 | GEO

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Transcriptomic (DNA microarray) and Metabolome (LC-TOF-MS) analyses of the liver in high-fat diet mice after intranasal administration of GALP (Galanin-Like Peptide)

Project description:The aim of this basic research is to test the efficacy of intranasal administration of Galanin-like Peptide (GALP) and its clinical application under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed body weight changes after intranasal administration of GALP in diet-induced obesity (DIO) mice.

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single cell RNA sequencing of migratory dendritic cells after intranasal adjuvant/tolerogen administration

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Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models

Project description:Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing transmission of SARS-CoV-2. We found that a single intranasal dose of serotype 5-based adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) secretory and serum anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and in respiratory secretions, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of wild-type mice from a challenge with the SARS-CoV-2 beta variant. Our data confirm and extend previous studies reporting promising preclinical results on vector-based intranasal SARS-CoV-2 vaccination, and support the potential of this approach to elicit mucosal immunity for preventing reinfection and transmission of SARS-CoV-2 more effectively than the currently available vaccines.

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Bambusa multiplex

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Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models

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Project description:Purpose: RNA sequencing of spinal cord following intranasal administration of miRNA-219 in Theiler’s murine encephalomyelitis virus (TMEV) model of multiple sclerosis Methods: RNA isolated from spinal cords was analyzed by Next-Generation RNA Sequencing (Illumina) Results: Here, we analyzed the therapeutic effects of miR-219 in a virus-induced demyelinating model. Following intranasal administration of miR-219 in TMEV-infected mice, we found significant reduction of clinical signs, virus persistence (virus genome copy numbers), neuroglia activation, proinflammatory cytokine levels, and demyelination. RNA sequencing of expressed host genes demonstrated that miR-219 potentiates transcriptional changes in cholesterol-related genes, leading to reduced levels of this lipid. Conclusions: Since virus replication relies on hijacking cholesterol biosynthesis and trafficking of host cell endogenous pools as well as remodeling intracellular membranes, i.e., the virus replication organelles or viroplasm, treatment with miR-219 may interfere with virus RNA replication through downregulation of cholesterol synthesis. Our findings show that miR-219 administration lessens pathological changes by reducing the CNS virus loads and favoring myelin repair.

2020-11-16 | GSE107091 | GEO

Intranasal Insulin Treatment Alters Gene Expression Profile in the Hippocampus of Rats with Perinatal Iron Deficiency

Project description:Background: Perinatal iron deficiency (ID) targets the hippocampus and leads to long-term cognitive deficits. These deficits remain even after iron repletion, suggesting that further insight into the mechanisms of cognitive deficits and adjunct treatments are needed. Intranasal insulin improves cognitive deficits in adult humans with Alzheimer’s disease and type 2 diabetes and could provide benefits in ID-induced neurological dysfunction. Objective: Assess the effects of intranasal insulin administration on the hippocampal transcriptome in rat model of perinatal ID. Methods: Perinatal ID was induced using a low iron diet from gestational day 3 until postnatal day (P) 7, followed by an iron sufficient (IS) diet through P21. Intranasal insulin was administered at a dose of 0.3 IU, twice daily from P8 to P21. Hippocampi were removed on P21 from IS control, ID control, IS insulin, and ID insulin groups. Total RNA was isolated and profiled using TruSeq next-generation sequencing (Illumina). Gene expression profiles were characterized using custom Galaxy workflows and expression patterns were examined using Ingenuity Pathways Analysis (Qiagen) (n = 7-9 per group). Results: Transcriptomic profiling revealed that mitochondrial biogenesis and flux, oxidative phosphorylation, quantity of neurons, CREB signaling in neurons, and RICTOR-based mTOR signaling were disrupted with ID and positively affected by insulin treatment with the most benefit observed in the ID insulin group. Conclusions: Both perinatal ID and insulin administration altered gene expression in the developing hippocampus. Intranasal insulin treatment reversed the adverse effects of ID on many molecular pathways and should be further explored as an adjunct therapy in perinatal ID.

2023-04-20 | GSE220770 | GEO

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