Time-course transcriptome analysis of lungs from mice exposed to ricin by intratracheal inoculation

Jiao, Zhouguang; Li, Sha; Su, Duo; Gan, Changjiao; Zhao, Xiaodong; Gao, Bo; Qiu, Yefeng; Song, Yajun; Zhou, Dongsheng; Hu, Lingfei; Yang, Huiying

doi:10.1016/j.toxlet.2020.11.012

Cited by 8 publications

(7 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, finding new targets for the treatment of ALI induced by RT inhalation is of major clinical importance. Previous work from our laboratory has shown that expression levels of multiple pro-inflammatory cytokines and transcription factors increased significantly at the early stage of RT-induced ALI (4 h post-exposure) ( 6 ). Parajuli et al.…”

Section: Discussionmentioning

confidence: 94%

“…New therapeutics are urgently needed to effectively treat pulmonary RT toxicity. Emerging evidence suggests that the dramatic inflammatory response induced by RT exposure is the leading cause of mortality ( 6 , 7 ). Pulmonary ricin toxicity is characterized by a lung pathology associated with a “cytokine storm” ( 8 – 10 ) that is directly caused by an imbalance between pro-inflammatory and anti-inflammatory cytokines ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice

Zong

Wang

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Specific therapeutics are not available for acute lung injury (ALI) induced by ricin toxin (RT). Inhibiting the host immune response in the course of pulmonary ricinosis is hypothesized to be of benefit and can be achieved by impairing granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, thereby reducing the pro-inflammatory response to exogenous foreign body invasion. However, it is unknown whether mice with impaired GM-CSF signaling can survive after RT inhalation. To test this, colony stimulating factor 2 receptor alpha (Csf2ra) knockout (KO) mice that lack GM-CSF signaling and wild-type (WT) mice models of intratracheal exposure to a lethal dose (2× LD50) of RT were established. Survival was greater in Csf2ra KO mice 21 days after RT inhalation compared with WT mice. Highly co-expressed genes that probably attenuated the pro-inflammatory response in the lung of Csf2ra KO mice were identified. Bioinformatics analysis revealed that transcriptome changes involved mostly inflammation-related genes after RT exposure in both Csf2ra KO mice and WT mice. However, the activity levels of pro-inflammatory pathways, such as the TNF signaling pathway and NF-κB signaling pathway, in Csf2ra KO mice were significantly decreased and the degree of neutrophil chemotaxis and recruitment inhibited after RT-exposure relative to WT mice. RT-qPCR and flow cytometry validated results of RNA-Seq analysis. This work provides potential avenues for host-directed therapeutic applications that can mitigate the severity of ALI-induced by RT.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice

Zong

Wang

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previously, transcriptomic analysis was successfully used to identify DEGs in a mouse pulmonary poisoning model established using an intratracheal injection of ricin [ 22 ]. The results obtained in that study indicated that the expression levels of numerous genes related to leukocyte migration and chemotaxis increase continuously after exposure to ricin.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Rat Lungs Exposed to Moxa Smoke after Acute Toxicity Testing

Deng

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

The increasing use of moxibustion has led to a debate concerning the safety of this treatment in human patients. Inhalation of cigarette smoke induces lung inflammation and granulomas, the proliferation of alveolar epithelial cells, and other toxic effects; therefore, it is important to assess the influence of inhaled moxa smoke on the lungs. In the present study, a novel poisoning cabinet was designed and used to assess the acute toxicity of moxa smoke in rats. We evaluated pathological changes in rat lung tissue and analyzed differentially expressed genes (DEGs) using RNA-seq and transcriptomic analyses. Our results show that the maximum tolerable dose of moxa smoke was 290.036 g/m³ and LC50 was 537.65 g/m³. Compared with that of the control group, the degree of inflammatory cell infiltration in the lung tissues of group A rats (all dead group) was increased, while that in group E rats (all live group) remained unchanged. GO and KEGG enrichment analyses showed that the DEGs implicated in cell components, binding, and cancer were significantly enriched in the experimental groups compared with the profile of the control group. The expressions of MAFF, HSPA1B, HSPA1A, AOC1, and MX2 determined using quantitative real-time PCR were similar to those determined using RNA-seq, confirming the reliability of RNA-seq data. Overall, our results provide a basis for future evaluations of moxibustion safety and the development of moxibustion-based technology.

show abstract

“…The histopathological analyses were performed according to standard operating procedures as described in a previously published paper [ 29 ]. Briefly, the heart, lung, spleen, liver, and kidney were dehydrated and embedded using paraffin, sliced into approximately 5 μm sections and placed on glass slides.…”

Section: Methodsmentioning

confidence: 99%

Expression of TFRC helps to improve the antineoplastic effect of Ara-C on AML cells through a targeted delivery carrier

Jiao

Zhang

et al. 2023

J Nanobiotechnol

Self Cite

View full text Add to dashboard Cite

Background Currently, high doses of cytarabine arabinoside (Ara-C)-based combined chemotherapy are commonly used in acute myeloid leukemia (AML) therapy, but severe adverse effects and poor suppression effects in leukemia cells limit the clinical therapeutic efficiency of Ara-C-based chemotherapy due to a lack of targeting selectivity. To improve the therapeutic effect of Ara-C in AML, here, since we confirmed that transferrin receptor 1 (TFRC) expression in AML cells was constant, we generated Ara-C@HFn by encapsulating free Ara-C into self-assembled heavy ferritin chain (HFn, the ligand of TFRC) nanocages. Results The analysis of clinically relevant data suggested that the high expression levels of TFRC from AML cells would not decrease significantly after treatment with Ara-C. Ara-C@HFn can be efficiently internalized by leukemia cells, showing stronger cytotoxic effects in vitro and reducing the burden of leukemia in AML mice more effectively in vivo than free Ara-C. Ara-C@HFn treatment showed no acute toxicity in visceral organs of mice. Moreover, the analysis of clinically relevant data also suggested that there are several drugs (such as tamibarotene and ABT199) that would not cause significant expression down-regulation of TFRC in AML cells (after treatment). Conclusion The above results suggested that TFRC can be used as a constant and effective target for drug targeting delivery of AML cells. Thus Ara-C@HFn treatment can become a safe and efficient strategy for AML therapy by specifically delivering Ara-C to AML cells. Besides, the HFn nanocages are promising for improving antineoplastic effect of other AML-related therapy drugs that do not cause downregulated expression of TFRC in AML cells. Graphical Abstract

show abstract

Time-course transcriptome analysis of lungs from mice exposed to ricin by intratracheal inoculation

Cited by 8 publications

References 45 publications

Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice

Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice

Transcriptome Analysis of Rat Lungs Exposed to Moxa Smoke after Acute Toxicity Testing

Expression of TFRC helps to improve the antineoplastic effect of Ara-C on AML cells through a targeted delivery carrier

Contact Info

Product

Resources

About