Extensive modulation of inflammatory and axonal genes led to robust axon regeneration in severe benzalkonium chloride-injured corneas treated with cord blood-derived biologics
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ABSTRACT:
PROVIDER: PRJNA1010670 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25786740.fastq.gz | Fastqsanger.gz | |||
| SRR25786741.fastq.gz | Fastqsanger.gz | |||
| SRR25786742.fastq.gz | Fastqsanger.gz | |||
| SRR25786743.fastq.gz | Fastqsanger.gz | |||
| SRR25786744.fastq.gz | Fastqsanger.gz |
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Project description:Modern ophthalmic solutions contain benzalkonium chloride (BAK), a potent antimicrobial preservative, that chronically damages the ocular apparatus. Umbilical cord blood serum (UCS) and platelet-rich plasma (UCPRP) are promising treatments for BAK-injured corneas. Here, for the first time, the feasibility of using both of these biologics for corneal treatment was demonstrated. Using animal studies and RNA-seq analysis, it was validated that severe BAK injury led to the upregulation of innate and adaptive immune responses, which corresponded to morphological and pathological changes in the cornea. When UCS and UCPRP were administered, besides significant corneal recovery, widespread immune pathways downregulation was observed. Subsequent verification of some of the genes involved in two of the most notable KEGG pathways suggested that the amelioration of inflammation was likely due to the reduction of immune cells, the decrease in chemoattractants, as well as the lessening of pro-inflammatory MMPs. Besides that, regulation of several key axonal genes led to robust axon recovery that correlated to nearly restored corneal sensitivity. Thus, these findings demonstrated the viability of cord blood-derived therapeutics for treating sustained, BAK-induced injuries in the cornea and also provided evidence that an optimal level of inflammatory response is crucial for stimulating axon regeneration.
2024-09-06 | GSE241879 | GEO
Project description:The goal of this Tn-Seq study was to determine important determinants of Acinetobacter baumannii tolerance of sub-MIC concentrations of benzalkonium chloride. This Tn-seq data was then utilized to aide in the determination of the sub-MIC mechanism of action for benzalkonium chloride.
2018-01-23 | GSE96745 | GEO
Project description:The goal of this RNA-Seq study was to determine Acinetobacter baumannii's transcriptiional response to sub-MIC concentrations of benzalkonium chloride in Acinetobacter baumannii. This RNA-seq data was then utilized to aide in the determination of the sub-MIC mechanism of action for benzalkonium chloride.
2018-01-23 | GSE96746 | GEO
Project description:BackgroundUmbilical cord blood-derived therapeutics, such as serum (UCS) and platelet-rich plasma (UCPRP), are popular treatment options in clinical trials and can potentially be utilized to address a clinically unmet need caused by preservatives, specifically benzalkonium chloride (BAK), present in ophthalmic formulations. As current clinical interventions for secondary injuries caused by BAK are suboptimal, this study will explore the feasibility of utilizing UCS and UCPRP for cornea treatment and investigate the underlying mechanisms associated with this approach.MethodsMice's corneas were administered BAK to induce damage. UCS and UCPRP were then utilized to attempt to treat the injuries. Ocular tests were performed on the animals to evaluate recovery, while immunostaining, RNA-seq, and subsequent bioinformatics analysis were conducted to investigate the treatment mechanism.ResultsBAK administration led to widespread inflammatory responses in the cornea. Subsequent treatment with UCS and UCPRP led to the downregulation of immune-related 'interactions between cytokine receptors' and 'IL-17 signaling' pathways. Although axonal enhancers such as Ngf, Rac2, Robo2, Srgap1, and Rock2 were found to be present in the injured group, robust axonal regeneration was observed only in the UCS and UCPRP treatment groups. Further analysis revealed that, as compared to normal corneas, inflammation was not restored to pre-injury levels post-treatment. Importantly, Neuropeptide Y (Npy) was also involved in regulating immune responses, indicating neuroimmune axis interactions.ConclusionsCord blood-derived therapeutics are feasible options for overcoming the sustained injuries induced by BAK in the cornea. They also have potential applications in areas where axonal regeneration is required.
| S-EPMC10763178 | biostudies-literature
Project description:Transcriptomic profiling was conducted on the adrenal glands, heart, and pancreas 24 hours after the 10th intratracheal instillation of benzalkonium chloride in rats. Total RNA was extracted using TRIzol and purified with the RNeasy Mini kit. High-quality RNA (RIN > 9) was used to construct sequencing libraries with the TruSeq Stranded mRNA kit, followed by sequencing on a NovaSeq 6000 platform.
2025-10-19 | GSE300975 | GEO
Project description:Benzalkonium chloride (BC) is a commonly used disinfectant and preservative. This study describes changes in expression level on the transcriptomic and proteomic level for Escherichia coli K12 gradually adapted to a tolerance level towards BC of 7-8 times the initial MIC. Results from DNA arrays and two-dimensional (2-DE) gel electrophoresis for global gene and protein expression studies were confirmed by real time quantitative PCR. Peptide mass fingerprinting by MALDI-TOF MS was used to identify differentially expressed proteins. Changes in expression level in adapted cells were shown for porins, drug transporters, glycolytic enzymes, ribosomal subunits and several genes and proteins involved in protection against oxidative stress and antibiotics. Adapted strains showed increased tolerance to several antibiotics. In conclusion, E. coli K12 adapted to higher tolerance to BC, acquired several general resistance mechanisms including responses normally related to the multiple antibiotic resistance (Mar) regulon and protection against oxidative stress. The results revealed that BC treatment might result in superoxide stress in E. coli. Keywords: Study of resistance mechanism
2007-05-23 | GSE6712 | GEO
Project description:Purpose: We compared the levels of miRNA specific for DEGs in isograft corneas with those in normal corneas, as well as the levels of miRNA specific for DEGs in allograft corneas with those in isograft corneas, to gain a better understanding of molecular variables that affect corneal graft rejection pathways. Methods: Illumina Hiseq 2500 deep sequencing was used to screen for differentially expressed genes (DEGs) in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Potential target genes among the DEGs were predicted using target prediction software (TargetScan, Miranda, miRDB, and CLIP), and the overlay portion was analyzed using the Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG). An analysis of the interactions between DEG proteins (PPI analysis) and a MetaCore software analysis. Results: Our results showed that 22 miRNAs were significantly upregulated and 4 were significantly downregulated in the isograft group when compared with the control group (P < 0.01), while 17 miRNAs were significantly upregulated and 3 were significantly downregulated in the allograft group when compared with the isograft group (P < 0.01). Among the miRNAs with altered expression levels, miR-155-5p, miR-142-3p, miR-142-5p, and miR-223-3p displayed simultaneous changes in the above two comparisons. Potential target genes among the DEGs were predicted using target prediction software, and the overlay portion was analyzed using the Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG). GO and KEGG analyses showed that the DEGs were mainly involved in metabolic pathways, cytokine secretion, and tumor immunity functions. An analysis of the interactions between DEG proteins (PPI analysis) and a MetaCore software analysis of 4 key DEGs revealed that the genes regulated by miR-155-5p played important roles in the miRNA-mRNA regulatory network. Furthermore, the MetaCore analysis identified C/EBP beta, p53, and sp1 as key transcription factors in that network. Conclusions: Our study identified transplanted corneas-specific miRNA in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Furthermore, bioinformatics analysis of the key miRNA regulatory network revealed the molecular mechanisms, which suggests miRNAs may as new molecular targets for treating corneal injuries and corneal transplant rejection
2018-04-28 | GSE113787 | GEO
Project description:Characteristic structural details of the cornea are transparency, the absence of blood vessels, and the presence of numerous sensory nerve endings. The corneal epithelium is one of the most densely innervated tissues of the body. The characteristics of the cornea are established during fetal development, and are lost in adult life when the cornea regenerates after injury. The common reaction of the cornea to injury is the formation of opaque scars, the ingrowth of blood vessels, and distinct changes in the innervation pattern. Scar formation of the cornea is critically modulated by the expression of transforming growth factor-beta (TGF-beta). To identify genes that are important for corneal transparency, dense innervation and absence of blood vessels by comparing corneas from wildtype mice with those that are under the influence of high doses of TGF-beta. Transparency, dense innervation, and absence of blood vessels in the cornea all depend on the expression of a critical set of genes that are not expressed when TGF-beta is present. Mice were generated that overexpress TGF-beta under control of a strong lens-specific promoter. These mice developed opaque corneas that are vascularized and lack sensory nerves. In addition, these corneas were densely populated with cells expressing neural cell adhesion protein. RNA was isolated from corneas of transgenic animals and wildtype littermates in order to analyze differentially expressed genes and to identify those that are only expressed in transparent, avascular, and densely innervated wildtype corneas.
2008-06-15 | E-GEOD-6676 | biostudies-arrayexpress
Project description:A comprehensive comparative analysis of antifungal potential of benzalkonium chloride and newly synthesized fullerenol/benzalkonium chloride nanocomposite was conducted to assess the possible impact of carbon-based nanocarrier on antimicrobial properties of the commonly used biocide. Physical characterization of synthesized nanocomposite showed zeta potential of +37.4 mV and inhomogeneous particles size distribution, with nanocomposite particles' dimensions within 30-143 nm and maximum number of particles at 44 nm. The effect of pure and fullerenol nanocarrier-bound biocide was evaluated in eight Aspergillus species. In mycelial growth assay, nanocomposite was more potent, as fungicidal effect of 1.04/0.6 μg mL(-1) was obtained in all but one of the isolates (A. niger), while proportional concentration of pure biocide (0.6 μg mL(-1)) completely inhibited mycelial growth of only three Aspergillus species. However, conidia appear to be less susceptible to nanocomposite treatment, as lower fungistatic (MIC) and fungicidal (MFC) concentrations were obtained with biocide alone (MIC in range from 0.03 to 0.15 μg mL(-1) and MFC from 0.075 to 0.45 μg mL(-1)). To a different degree, both substances stimulated aflatoxin B1 production and inhibited ochratoxin A synthesis. Very low mycelium biomass yield, in range from 1.0 to 3.0 mg dry weight, was documented in both biocide and nanocomposite enriched medium.
| S-EPMC4532958 | biostudies-other
Project description:Tn-Seq and RNA-seq of Benzalkonium Chloride Treated and Untreated Acinetobacter baumannii
| PRJNA380083 | ENA