Inhibiting miR-129-5p alleviates inflammation and modulates autophagy by targeting ATG14 in fungal keratitis

Lin, Jingqiong; Lin, Yi; Huang, Yurong; Hu, Jianzhang

doi:10.1016/j.exer.2021.108731

Cited by 7 publications

(8 citation statements)

References 33 publications

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“…Currently, miRNAs are recognized to regulate a variety of important physiological and pathological processes, including growth, cell death and tumor formation, and to play important roles in regulating host immune responses against infections. Recently, miR129 has also been identified as a novel regulator of inflammation in different disease conditions and can be regulated through HMGB1/TLR4/NF-κB signaling, which inhibits apoptosis and inflammation [ 32 ], thereby attenuating spinal cord injury in mice. The increase in miR129 expression protected against blood reperfusion by reducing inflammation induced neuronal and blood spinal cord barrier injury via suppression of HMGB1 and TLR3-related cytokines.…”

Section: Resultsmentioning

confidence: 99%

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Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury

Zhou

Du²,

Luo³

et al. 2022

J Nanobiotechnol

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Radiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.

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Section: Resultsmentioning

confidence: 99%

“…Lin [ 32 ] has indicated that the dual luciferase reporter assay indicates that Atg14 is a direct target of miR129. This illustrates that miR129 is a novel small molecule that regulates autophagy by targeting Atg14, suggesting that it might be a proinflammatory and therapeutic target for fungal keratitis.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury

Zhou

Du²,

Luo³

et al. 2022

J Nanobiotechnol

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“…19 However, combined treatment has been recommended in clinical practice since natamycin has a poor effect on some patients with severe fungal infections. 20 In our study, on the basis of natamycin treatment, voriconazole was added to treat patients with FK. According to the results of our study, the combined use of natamycin and voriconazole in the treatment of FK patients can effectively remove ocular fungi, promote the improvement of ocular symptoms and visual acuity, and has good safety without influence in increasing the adverse reactions.…”

Section: Discussionmentioning

confidence: 99%

Natamycin versus natamycin combined with voriconazole in the treatment of fungal keratitis

Cai¹,

Yang²,

Wei

et al. 2023

Pak J Med Sci

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Objective: To observe the therapeutic effect of natamycin combined with voriconazole in the treatment of fungal keratitis (FK). Methods: This is a retrospective study. The subjects of this study were 64 patients with FK who were admitted to Baoding No.1 Central Hospital from February 2019 to July 2022. The enrolled patients were divided into control group (n= 32) and study group (n= 32) by the random number table method. The control group was treated with natamycin alone, and the study group was treated with natamycin combined with voriconazole. The total efficacy, time of disappearance of ocular symptoms, visual acuity level, keratitis severity score, corneal ulcer area, tear fungus index and incidence of adverse reactions were compared between the two groups. Results: The total efficacy,of the study group was significantly higher than that of the control group. The disappearance time of corneal ulcer, photophobia, foreign body sensation and hypopyon in the study group was shorter than those in the control group. Keratitis severity score and (1,3)-β-D-glucan level in the study group were lower than those in the control group. The corneal ulcer area was narrowed in the study group than that of the control group, and the visual acuity level in the former group was higher than that of the latter group. Besides, there was no significant difference in the frequency of adverse reactions between the two groups. Conclusion: Natamycin combined with voriconazole is safe and effective in the treatment of FK. doi: https://doi.org/10.12669/pjms.39.3.6908 How to cite this: Cai J, Yang C, Wei Q, Lian H, An L, Zhang R. Natamycin versus natamycin combined with voriconazole in the treatment of fungal keratitis. Pak J Med Sci. 2023;39(3):775-779. doi: https://doi.org/10.12669/pjms.39.3.6908 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“… 38 Recent studies have illustrated that autophagy also plays a key role in the pathologic progress of FK. 39 Autophagy can reduce the severity of A. fumigatus keratitis by regulating the recruitment of neutrophils and balancing the production of proinflammatory and anti-inflammatory cytokines. 21 Likewise, our study also found that autophagic flux was restrained in the cornea of a FK model.…”

Section: Discussionmentioning

confidence: 99%

MiR-223-3p Regulates Autophagy and Inflammation by Targeting ATG16L1 in Fusarium solani–Induced Keratitis

Tang

Lin

Huang

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Increasing evidence suggested that microRNAs (miRs) are implicated in the regulation of the inflammatory response and autophagy in multiple diseases. The present study aimed to explore the effect of miR-223-3p on inflammation and autophagy in fungal keratitis (FK). Methods An FK mouse model was established, and primary corneal stromal cells were isolated by inoculation with Fusarium solani . The expression of miR-223-3p was determined by quantitative RT-PCR. Subsequently, the target gene of miR-223-3p was identified by a dual-luciferase reporter assay. The levels of miR-223-3p were altered by transfecting miR agomir/antagomir to evaluate its effects. Slit-lamp biomicroscopy and hematoxylin and eosin staining were employed to detect corneal damage. The levels of autophagy were assessed by immunofluorescence, Western blotting, mRFP-GFP-LC3 fluorescence microscopy, and electron microscopy. In addition, inflammation was demonstrated by determining the proinflammatory mediators IL-1β and TNF-ɑ. Results Our data suggested that miR-223-3p was increased and that autophagic flux was impaired in mouse FK. Then, we confirmed that autophagy-related gene 16L1 (ATG16L1) was a potential target of miR-223-3p and that this miR negatively regulated the expression of ATG16L1. The inhibition of miR-223-3p attenuated inflammation in FK, reduced P62 expression, and increased the ratio of LC3-II/LC3-I, whereas the overexpression of miR-223-3p displayed the opposite results. Conclusions Taken together, miR-223-3p might regulate autophagy via targeting ATG16L1 in experimental F. solani keratitis and is associated with the inflammatory response. MiR-223-3p might be a potential therapeutic target for FK.

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Inhibiting miR-129-5p alleviates inflammation and modulates autophagy by targeting ATG14 in fungal keratitis

Cited by 7 publications

References 33 publications

Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury

Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury

Natamycin versus natamycin combined with voriconazole in the treatment of fungal keratitis

MiR-223-3p Regulates Autophagy and Inflammation by Targeting ATG16L1 in Fusarium solani–Induced Keratitis

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