1.Mechanism of isorhamnetin in alleviating acute lung injury by regulating pyroptosis medicated by NLRP3/ASC/caspase-1 axis.
Ya-Lei SUN ; Yu GUO ; Xin-Yu WANG ; Ya-Su ZHANG ; Xue CHENG ; Ke ZHU ; Li-Dian CHEN ; Xiao-Dong FENG
China Journal of Chinese Materia Medica 2025;50(15):4120-4128
This study aims to explore the intervention effects of isorhamnetin(Isor) on acute lung injury(ALI) and its regulatory effects on pyroptosis mediated by the NOD-like receptor family pyrin domain containing 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteine aspartate-specific protease-1(caspase-1) axis. In the in vivo experiments, 60 BALB/c mice were divided into five groups. Except for the control group, the other groups were administered Isor by gavage 1 hour before intratracheal instillation of LPS to induce ALI, and tissues were collected after 12 hours. In the in vitro experiments, RAW264.7 cells were divided into five groups. Except for the control group, the other groups were pretreated with Isor for 2 hours before LPS stimulation and subsequent assessments. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung tissue, while lung swelling, protein levels in bronchoalveolar lavage fluid(BALF), and myeloperoxidase(MPO) levels in lung tissue were measured. Cell proliferation toxicity and viability were assessed using the cell counting kit-8(CCK-8) method. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin-1β(IL-1β), IL-6, IL-18, and tumor necrosis factor-α(TNF-α). Protein levels of NLRP3, ASC, cleaved caspase-1, and the N-terminal fragment of gasdermin D(GSDMD-N) were evaluated using immunohistochemistry, immunofluorescence, and Western blot. The results showed that in the in vivo experiments, Isor significantly improved pathological damage in lung tissue, reduced lung swelling, protein levels in BALF, MPO levels in lung tissue, and levels of inflammatory cytokines such as IL-1β, IL-6, IL-18, and TNF-α, and inhibited the high expression of the NLRP3/ASC/caspase-1 axis and the pyroptosis core gene GSDMD-N. In the in vitro experiments, the safe dose of Isor was determined through cell proliferation toxicity assays. Isor reduced cell death and inhibited the expression levels of the NLRP3/ASC/caspase-1 axis, GSDMD-N, and inflammatory cytokines. In conclusion, Isor may alleviate ALI by modulating pyroptosis mediated by the NLRP3/ASC/caspase-1 axis.
Animals
;
Pyroptosis/drug effects*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Acute Lung Injury/physiopathology*
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Mice
;
Mice, Inbred BALB C
;
Quercetin/pharmacology*
;
Caspase 1/genetics*
;
CARD Signaling Adaptor Proteins/genetics*
;
Male
;
RAW 264.7 Cells
;
Humans
;
Lung/metabolism*
2.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
3.Parkinsonism in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Clinical Features and Biomarkers
Chih-Hao CHEN ; Te-Wei WANG ; Yu-Wen CHENG ; Yung-Tsai CHU ; Mei-Fang CHENG ; Ya-Fang CHEN ; Chin-Hsien LIN ; Sung-Chun TANG
Journal of Stroke 2025;27(1):122-127
4.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
5.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
6.Parkinsonism in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Clinical Features and Biomarkers
Chih-Hao CHEN ; Te-Wei WANG ; Yu-Wen CHENG ; Yung-Tsai CHU ; Mei-Fang CHENG ; Ya-Fang CHEN ; Chin-Hsien LIN ; Sung-Chun TANG
Journal of Stroke 2025;27(1):122-127
7.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
8.Parkinsonism in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Clinical Features and Biomarkers
Chih-Hao CHEN ; Te-Wei WANG ; Yu-Wen CHENG ; Yung-Tsai CHU ; Mei-Fang CHENG ; Ya-Fang CHEN ; Chin-Hsien LIN ; Sung-Chun TANG
Journal of Stroke 2025;27(1):122-127
9.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
10.Carbon-friendly ecological cultivation mode of Dendrobium huoshanense based on greenhouse gas emission measurement.
Di TIAN ; Jun-Wei YANG ; Bing-Rui CHEN ; Xiu-Lian CHI ; Yan-Yan HU ; Sheng-Nan TANG ; Guang YANG ; Meng CHENG ; Ya-Feng DAI ; Shi-Wen WANG
China Journal of Chinese Materia Medica 2025;50(1):93-101
Ecological cultivation is an important way for the sustainable production of traditional Chinese medicine in the context of the carbon peaking and carbon neutrality goals. Facility cultivation and simulative habitat cultivation modes have been developed and applied to develop the endangered Dendrobium huoshanense on the basis of protection. However, the differences in the greenhouse gas emissions and global warming potential of these cultivation modes remain unexplored, which limits the accurate assessment of carbon-friendly ecological cultivation modes of D. huoshanense. Greenhouse gas emission flux monitoring based on the static chamber method provides an effective way to solve this problem. Therefore, this study conducted a field experiment in the facility cultivation and simulative habitat cultivation modes at a D. huoshanense cultivation base in Dabie Mountains, Anhui Province. From April 2023 to March 2024, samples of greenhouse gases were collected every month, and the concentrations of CO_2, CH_4, and N_2O of the samples were then detected by gas chromatography. The greenhouse gas emission fluxes, cumulative emissions, and global warming potential were further calculated, and the following results were obtained.(1)The two cultivation modes of D. huoshanense showed significant differences in greenhouse gas emission fluxes, especially the CO_2 emission flux, with a pattern of facility cultivation>simulative habitat cultivation [(35.60±11.70)mg·m~(-2)·h~(-1) vs(2.10±4.59)mg·m~(-2)·h~(-1)].(2) The annual cumulative CO_2 emission flux in the case of facility cultivation was significantly higher than that of simulative habitat cultivation[(3 077.00±842.00)kg·hm~(-2) vs(221.00±332.00)kg·hm~(-2)], while no significant difference was found in annual cumulative CH_4 and N_2O emission fluxes.(3) The facility cultivation mode had a significantly higher global warming potential than the simulative habitat cultivation mode [(3 053.00±847.00)kg·hm~(-2) vs(196.00±362.00)kg·hm~(-2)]. Overall, the simulative habitat cultivation of D. huoshanense has obvious carbon-friendly characteristics compared with facility cultivation, which is in line with the concept of ecological cultivation of medicinal plants. This study is of great reference significance for the implementation and promotion of the ecological cultivation mode of D. huoshanense under carbon peaking and carbon neutrality goals.
Dendrobium/chemistry*
;
Greenhouse Gases/metabolism*
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Carbon/analysis*
;
Ecosystem
;
Carbon Dioxide/metabolism*
;
China
;
Global Warming

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