The role and therapeutic potential of itaconate in lung disease DOI Creative Commons
Ruyuan He,

Yifan Zuo,

Ke Yi

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Oct. 1, 2024

Language: Английский

Itaconate in host inflammation and defense DOI
Dan Ye, Pu Wang, Leilei Chen

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(7), P. 586 - 606

Published: March 5, 2024

Language: Английский

Citations

18

Regulation of metabolic microenvironment with a nanocomposite hydrogel for improved bone fracture healing DOI Creative Commons
Kangkang Zha,

Meijun Tan,

Yiqiang Hu

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 37, P. 424 - 438

Published: April 24, 2024

Bone nonunion poses an urgent clinical challenge that needs to be addressed. Recent studies have revealed the metabolic microenvironment plays a vital role in fracture healing. Macrophages and bone marrow-derived mesenchymal stromal cells (BMSCs) are important targets for therapeutic interventions fractures. Itaconate is TCA cycle metabolite has emerged as potent macrophage immunomodulator limits inflammatory response. During osteogenic differentiation, BMSCs tend undergo aerobic glycolysis metabolize glucose lactate. Copper ion (Cu2+) essential trace element participates metabolism may stimulate promote osteogenesis. In this study, we develop 4-octyl itaconate (4-OI)@Cu@Gel nanocomposite hydrogel can effectively deliver release 4-OI Cu2+ modulate improve functions of involved healing process. The findings reveal burst reduces response, promotes M2 polarization, alleviates oxidative stress, while sustained stimulates BMSC differentiation enhances endothelial cell angiogenesis. Consequently, 4-OI@Cu@Gel system achieves rapid mice. Thus, study proposes promising regenerative strategy expedite through reprogramming macrophages BMSCs.

Language: Английский

Citations

9

Alirocumab boosts antioxidant status and halts inflammation in rat model of sepsis-induced nephrotoxicity via modulation of Nrf2/HO-1, PCSK9/HMGB1/NF-ᴋB/NLRP3 and Fractalkine/CX3CR1 hubs DOI Open Access

Noha F. Hassan,

Mona R. El‐Ansary,

Heba Mohammed Refat M. Selim

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116929 - 116929

Published: June 17, 2024

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, study aimed elucidate antibacterial effect alirocumab against E. coli vitro. Additionally, evaluation potential nephroprotective effects LPS-induced AKI rats, highlighting underlying mechanisms involved these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; normal control group, whereas sepsis-mediated induced II III through single-dose intraperitoneal injection LPS on day 16. In group III, animals given alirocumab. The results revealed mitigated alirocumab, evidenced amelioration renal function tests (creatinine, cystatin C, KIM-1, NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, MDA); apoptotic markers histopathological findings. Besides, pronouncedly hindered LPS-mediated response, confirmed diminishing HMGB1, TNF-α, IL-1β, caspase-1 contents; gene expression RAGE, NF-ᴋB Fractalkine/CX3CR1, along mRNA TLR4, MYD88, NLRP3. Regarding actions, showed displayed anti-bacterial activity pathogenic gram-negative coli. conclusion, elicited activities via modulation Nrf2/HO-1, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 axes.

Language: Английский

Citations

8

IRG1/itaconate alleviates acute liver injury in septic mice by suppressing NLRP3 expression and its mediated macrophage pyroptosis via regulation of the Nrf2 pathway DOI
Pei Zhou, Lei Yang, Ruidong Li

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 135, P. 112277 - 112277

Published: May 23, 2024

Language: Английский

Citations

7

Rhizoma Paridis saponins attenuate Gram‐negative bacteria‐induced inflammatory acne by binding to KEAP1 and modulating Nrf2 and MAPK pathways DOI Creative Commons
Yang Yang, Chaofan Wang, Juan Wang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(6)

Published: March 1, 2024

Abstract Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with altered skin microbiome. Recent studies have implicated profound role Gram‐negative bacteria in acne development, but there lack antiacne agents targeting these bacteria. Polyphyllins are major components Rhizoma Paridis great anti‐inflammatory potential. In this study, we aimed to evaluate effects and underlying mechanisms PPH PPH‐enriched extract (RPE) treating bacteria‐induced acne. RPE treatments significantly suppressed mRNA protein expressions interleukin (IL)‐1β IL‐6 lipopolysaccharide (LPS)‐induced RAW 264.7 HaCaT cells, along intracellular reactive oxygen species (ROS) generation. Furthermore, inhibited nuclear translocation factor kappa‐B (NF‐κB) P65 LPS‐induced cells. Based on molecular docking, could bind kelch‐like ECH‐associated 1 (KEAP1) protein. activate erythroid 2‐related 2 (NRF2) upregulate haem oxygenase‐1 (HO‐1). Moreover, mitogen‐activated kinase (MAPK) pathway. Therefore, showed antioxidative vitro, promising for alternative therapeutic.

Language: Английский

Citations

5

Nanoparticles transfected with plasmid-encoded lncRNA-OIP5-AS1 inhibit renal ischemia-reperfusion injury in mice via the miR-410-3p/Nrf2 axis DOI Creative Commons
Rongjie Zhang, Xin Zhang, Xuhui Zhu

et al.

Renal Failure, Journal Year: 2024, Volume and Issue: 46(1)

Published: Feb. 29, 2024

Nanostructures composed of liposomes and polydopamine (PDA) have demonstrated efficacy as carriers for delivering plasmids, effectively alleviating renal cell carcinoma. However, their role in acute kidney injury (AKI) remains unclear. This study aimed to investigate the effects plasmid-encoded lncRNA-OIP5-AS1@PDA nanoparticles (POP-NPs) on ischemia/reperfusion (RI/R) explore underlying mechanisms. RI/R or OGD/R models were established mice HK-2 cells, respectively. In vivo, vector POP-NPs administered (10 nmol, IV) 48 h after treatment. mouse model, OIP5-AS1 Nrf2/HO-1 expressions down-regulated, while miR-410-3p expression was upregulated. treatment reversed RI/R-induced tissue injury, restoring altered levels blood urea nitrogen, creatinine, malondialdehyde, inflammatory factors (IL-8, IL-6, TNF-α), ROS, apoptosis, miR-410-3p, well suppressed SOD model mice. Similar results obtained treated with POP-NPs. Additionally, mimics could reverse cellular models, partially counteracted by Nrf2 agonists. The binding relationship between alongside Nrf2, has been substantiated dual-luciferase reporter RNA pull-down assays. revealed that can attenuate through miR-410-3p/Nrf2 axis. These findings lay groundwork future targeted therapeutic approaches utilizing AKI.

Language: Английский

Citations

4

Manganese-Based Nanozyme Alleviates Acute Kidney Injury via Nrf2/HO-1 and PI3K/Akt/NF-κB Signaling Pathways DOI
Yang Zhang, Han Wang, K Liu

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Acute renal injury (AKI) has a high incidence rate and mortality, but current treatment methods are limited. As kind of nanomaterial with enzyme-like activity, nanozyme shown outstanding advantages in treating AKI according to recent reports. Herein, we assess the potential manganese-based nanozymes (MnO2-BSA NPs) excellent biosafety effectively alleviating AKI. Our findings vitro vivo reveal that MnO2-BSA NPs exert regulatory effects on oxidative stress, inflammation, apoptosis. These mediated through activation Nrf2/HO-1 PI3K/Akt/NF-κB pathways. Notably, it was observed cytoprotective effect is abrogated upon inhibition Nrf2 expression, highlighting important role this transcription factor cellular protection. In summary, study demonstrates protective provides molecular mechanisms involved, which can contribute advancement therapeutic interventions for nanozyme-based treatments.

Language: Английский

Citations

0

Patenting perspective on Keap1 inhibitors (2019-2024) DOI
Yue Luo, Wenlong Yang, Yuan Zhang

et al.

Expert Opinion on Therapeutic Patents, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Introduction Kelch-like ECH-associated protein 1 (Keap1), an E3 ligase negatively regulating the nuclear factor erythroid 2-related 2 (Nrf2), has emerged as auspicious drug target for treating ailments associated with oxidative stress and inflammation. Discovery of Keap1 inhibitors have attracted significant interest.

Language: Английский

Citations

0

Itaconate facilitates methane-induced Nrf2 pathway activation for mitigating liver ischemia and reperfusion injury DOI Creative Commons
Tianyi Zhang,

Dan-Feng Fan,

Kewei Qin

et al.

iLiver, Journal Year: 2025, Volume and Issue: unknown, P. 100144 - 100144

Published: Feb. 1, 2025

Language: Английский

Citations

0

Targeted inhibition of NEK7 preventing sepsis-induced cardiomyopathy by inhibiting NLRP3 inflammasome DOI

Lianghe Wen,

Zhen Quan,

Chunming Guan

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114245 - 114245

Published: Feb. 26, 2025

Language: Английский

Citations

0