IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

Zhu, Shi-Yong; Li, Chenxi; Tong, Yu-Xuan; Xu, Yaru; Wang, Zhaoyi; Li, Jinlong

doi:10.1039/d2fo01497a

Cited by 19 publications

(10 citation statements)

References 52 publications

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“…FOXO1 activation has been reported to be associated with a loss of CLDN5-dependent BBB integrity . It has already been demonstrated that atrazine (ATZ) exposure significantly raised the expression of FOXO1 in the thymus . Western blot analysis revealed that SFN therapy reduced FOXO1 expression, consistent with earlier research (Figure ).…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane Ameliorate Cadmium-Induced Blood–Thymus Barrier Disruption by Targeting the PI3K/AKT/FOXO1 Axis

Tong,

Zhu,

Wang

et al. 2024

J. Agric. Food Chem.

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Cadmium (Cd) is a transition metal ion that is extremely harmful to human and animal biological systems. Cd is a toxic substance that can accumulate in the food chain and cause various health issues. Sulforaphane (SFN) is a natural bioactive compound with potent antioxidant properties. In our study, 80 1 day-old chicks were fed with Cd (140 mg/kg BW/day) and/or SFN (50 mg/kg BW/day) for 90 days. The blood−thymus barrier (BTB) is a selective barrier separating T-lymphocytes from blood and cortical capillaries in the thymus cortex. Our research revealed that Cd could destroy the BTB by downregulating Wnt/β-catenin signaling and induce immunodeficiency, leading to irreversible injury to the immune system. The study emphasizes the health benefits of SFN in the thymus. SFN could ameliorate Cd-triggered BTB dysfunction and pyroptosis in the thymus tissues. SFN modulated the PI3K/AKT/FOXO1 axis, improving the level of claudin-5 (CLDN5) in the thymus to alleviate BTB breakdown. Our findings indicated the toxic impact of Cd on thymus, and BTB could be the specific target of Cd toxicity. The finding also provides evidence for the role of SFN in maintaining thymic homeostasis for Cd-related health issues.

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Section: Discussionmentioning

confidence: 99%

Sulforaphane Ameliorate Cadmium-Induced Blood–Thymus Barrier Disruption by Targeting the PI3K/AKT/FOXO1 Axis

Tong,

Zhu,

Wang

et al. 2024

J. Agric. Food Chem.

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“… 48 Furthermore, several studies have demonstrated the impact of STAT3 on pyroptosis through its influence on other targets, including AIM2 and GSDME. 49 , 50 Consequently, the modulation of STAT3 presents a promising therapeutic approach for mitigating sepsis-induced ARDS by suppressing macrophage pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

Mitigation of Sepsis-Induced Acute Lung Injury by BMSC-Derived Exosomal miR-125b-5p Through STAT3-Mediated Suppression of Macrophage Pyroptosis

Tao,

Xu,

Yang

et al. 2023

IJN

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Introduction Sepsis is a syndrome characterized by high morbidity and mortality rates. One of its most severe complications is acute lung injury, which exhibits a multitude of clinical and biological features, including macrophage pyroptosis. This study investigates the regulatory effects of exosomes derived from Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) on sepsis-associated acute lung injury (ALI) and explores the potential mechanisms mediated by exosomal miRNAs. Methods Exosomes were isolated from primary BMSCs of adult C57BL/6J mice using differential centrifugation. Their uptake and distribution in both in vitro and in vivo contexts were validated. Key sepsis-associated hub gene signal transducer and activator of transcription 3 (STAT3) and its upstream non-coding miR-125b-5p were elucidated through a combination of bioinformatics, machine learning, and miRNA sequencing. Subsequently, the therapeutic potential of BMSC-derived exosomes in alleviating sepsis-induced acute lung injury was substantiated. Moreover, the functionalities of miR-125b-5p and STAT3 were corroborated through miR-125b-5p inhibitor and STAT3 agonist interventions, employing gain and loss-of-function strategies both in vitro and in vivo. Finally, a dual-luciferase reporter assay reaffirmed the interaction between miR-125b-5p and STAT3. Results We isolated exosomes from primary BMSCs and confirmed their accumulation in the mouse lung as well as their uptake by macrophages in vitro. This study identified the pivotal sepsis-associated hub gene STAT3 and demonstrated that exosomes derived from BMSCs can target STAT3, thereby inhibiting macrophage pyroptosis. MiR-125b-5p inhibition experiments showed that exosomes mitigate macrophage pyroptosis and lung injury by delivering miR-125b-5p. STAT3 overexpression experiments validated that miR-125b-5p reduces macrophage pyroptosis and lung injury by suppressing STAT3. Furthermore, a dual-luciferase reporter assay confirmed the binding interaction between miR-125b-5p and STAT3. Conclusion Exosomes derived from BMSCs, serving as carriers for delivering miR-125b-5p, can downregulate STAT3, thereby inhibiting macrophage pyroptosis and alleviating sepsis-associated ALI. These significant findings provide valuable insights into the potential development of ALI therapies centred around exosomes derived from BMSC.

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“…The thymus and spleen are critical immune organs of the body. Changes in thymus and spleen indicators can visually reflect the body's immune function, and a decline in immune function is usually accompanied by atrophy of the immune organs 51,52 . RS and US could alleviate the suppression of the immune function of mice with CTX, and the lymphocytes of mice in the US feeding group increased more than those in the CTX + RS group.…”

Section: Discussionmentioning

confidence: 99%

Unrinsed Nemipterus virgatus surimi provides more nutrients than rinsed surimi and helps recover immunosuppressed mice treated with cyclophosphamide

et al. 2023

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BACKGROUND The rinsing process in the production of surimi can cause the loss of some important nutrients. To investigate the differences in nutritional properties between rinsed surimi (RS) and unrinsed surimi (US), this study compared the elemental composition, amino acid composition, fatty acid composition, proteomics, and an immunosuppression mouse model of surimi before and after rinsing, and analyzed the nutritional and immunological properties of RS and US. RESULTS The results showed that the protein, fat, and ash contents of RS were decreased compared with those of US; specifically, the contents of essential amino acids, semi‐essential amino acids, non‐essential amino acids, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids were decreased. In the non‐labeled quantitative proteomics analysis, three high‐abundance quantifiable protein contents and 68 low‐abundance quantifiable protein contents were found in RS (P‐values < 0.05, ratio > 2). Immune function experiments in mice revealed that both RS and US contributed to the recovery of immunity in immunocompromised mice. The effect of US was better than that of RS. CONCLUSION The rinsing process in surimi processing leads to the loss of nutrients in surimi. US promotes the recovery of immunity in immunocompromised mice more effectively than RS. © 2023 Society of Chemical Industry.

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IL-6/STAT3/Foxo1 axis as a target of lycopene ameliorates the atrazine-induced thymic mitophagy and pyroptosis cross-talk

Abstract: The thymus is central architecture for lymphoid cells. Atrazine exposure induces thymic mitophagy and pyroptosis cross-talk. Lycopene has the potential role in prevention the atrazine's toxic effect by targeting the IL-6/STAT3/Foxo1 axis.

Cited by 19 publications

References 52 publications

Sulforaphane Ameliorate Cadmium-Induced Blood–Thymus Barrier Disruption by Targeting the PI3K/AKT/FOXO1 Axis

Sulforaphane Ameliorate Cadmium-Induced Blood–Thymus Barrier Disruption by Targeting the PI3K/AKT/FOXO1 Axis

Mitigation of Sepsis-Induced Acute Lung Injury by BMSC-Derived Exosomal miR-125b-5p Through STAT3-Mediated Suppression of Macrophage Pyroptosis

Unrinsed Nemipterus virgatus surimi provides more nutrients than rinsed surimi and helps recover immunosuppressed mice treated with cyclophosphamide

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