Home Life Sciences RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
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RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway

  • Huilian Hua , Yao Quan , Zhiqin Li , Bo Pan , Fang Zhang , Jun Wang EMAIL logo , Jindong Li EMAIL logo and Su Jiang EMAIL logo
Published/Copyright: April 24, 2025
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Open Life Sciences
From the journal Open Life Sciences Volume 20 Issue 1

Abstract

RTA-408, also referred to as Omaveloxolone, is a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2) and has been demonstrated with protective effects against oxidative stress-induced injury. Oxidative stress is closely associated with the pathogenesis of hepatic ischemia reperfusion injury (HIRI). The aim of this study is to elucidate the impact and underlying mechanisms of RTA-408 in the process of HIRI. In the HIRI mice models, we found that RTA-408 improved liver function of HIRI mice and attenuated the HIRI-induced oxidative stress in vivo. Moreover, the neutrophil infiltration in liver tissues of HIRI mice was alleviated by the administration of RTA-408. RTA-408 treatment also rescued the elevated apoptosis in the liver tissues of HIRI mice. Furthermore, we demonstrated that RTA-408 treatment activated the Nrf2/HO-1 signaling pathway in liver tissues of HIRI mice. Furthermore, the HIRI mice models were developed using Nrf2-deficient mice to explore whether the protective effect of RTA-408 on HIRI was achieved through the activation of Nrf2. The results indicated that RTA-408 did not significantly alleviate the liver injury in Nrf2-deficient mice. Collectively, our results suggest that RTA-408 attenuates HIRI by improving liver function, and attenuating oxidative stress damage, apoptosis and inflammatory response possibly via the Nrf2/HO-1 pathway, which may provide a novel treatment strategy for HIRI patients.

Graphical abstract

Keywords: RTA-408; Nrf2; HO-1; oxidative stress; hepatic ischemia reperfusion injury

1 Introduction

Hepatic ischemia reperfusion injury (HIRI) is a severe and inevitable complication of some liver surgeries such as hepatectomy and liver transplantation due to the high dependence of liver on oxygen supply, which significantly affects the survival of patients [1,2]. HIRI is characterized by the initial blockade of blood flow to the liver, followed by the restoration of perfusion along with reoxygenation, which usually induces tissue damage and inflammatory responses and leads to liver dysfunction or failure [3]. The mechanisms involved in HIRI are complicated, including oxidative stress, cell death, inflammatory responses, and others [4].

For example, tumor necrosis factor (TNF) activates the extracellular signal-related kinase, c-Jun NH2-terminal kinase (JNK), and NF-B, which are potent inducers of inflammation. In addition to its proinflammatory role, TNF is an anti-tumor cytokine and was reported to activate NF-B formation [5]. Besides, there is a pathway, which can also lead to widespread protein destabilization and DNA damage through redox instability and shifts in energy homeostasis [6]. The status of liver function is often identified by assessing the alanine transaminase (ALT) and aspartate transaminase (AST) levels in blood serum. In instances where hepatocytes are subjected to damage, these enzymes leak into circulation and are consequently markers for liver damage [7].

Currently, it remains challenging to manage HIRI in clinical practice, and understanding its underlying mechanism is essential for the exploration of effective treatment methods.

Omaveloxolone (RTA-408) is a new synthetic oleanane triterpenoid compound, which is known as a powerful activator of Nrf2. Previous literature has revealed the anti-oxidant and anti-inflammatory properties of RTA-408 in clinical trials. For example, RTA-408 is demonstrated to be safe and effective on improving the neurological function in patients with Friedreich ataxia [5]. RTA-408 is also suggested to be safe and well tolerated in patients with advanced solid tumors and can activate the Nrf2 signaling in a dose-dependent way [8]. Moreover, multiple studies have demonstrated the cytoprotective effects of RTA-408 after injury. It is indicated that RTA-408 enhances microglial polarization by suppressing reactive oxygen species (ROS) production and activating Nrf2 in mice after intracerebral hemorrhage [9]. In addition, RTA-408 can attenuate the oxidative stress-induced damage in human retinal pigment epithelial cells via activating Nrf2 [10]. In our previous study, RTA-408 is found to improve the renal function, reduce ROS generation, and down-regulate the oxidative injury marker in mice with ischemia-reperfusion injury by activating Nrf2 and up-regulating the GSH biosynthetic enzyme [11]. Furthermore, RTA-408 is suggested with hepatoprotective functions in mice with nonalcoholic steatohepatitis, which are achieved by reducing inflammatory responses and fibrosis through Nrf2 [12]. However, the impact of RTA-408 on HIRI is rarely reported, which requires further investigations.

Nrf2 encodes a transcription factor that belongs to the basic leucine zipper (bZIP) family of proteins and regulates genes containing the antioxidant response element and encoding proteins implicated in the response to injury and inflammation [11]. Accumulating evidence has defined the cytoprotective role of Nrf2 in ischemic-reperfusion injuries, including HIRI, by reducing the oxidant stress damage and inflammatory responses [13,14,15]. Moreover, Nrf2-deficient mice are reported with enhanced inflammatory responses, higher ROS levels and severe injury in the HIRI mice models [16,17,18], suggesting the hepatoprotective functions of Nrf2 in liver injury.

The aim of the present study was to elucidate the impact and underlying mechanisms of RTA-408 in HIRI. We hypothesized that RTA-408 activated Nrf2 signaling to alleviate oxidative stress, mitigate inflammation, and improve liver function in HIRI mice. The findings of our work may provide theoretical basis for the application of RTA-408 in treating HIRI.

2 Materials and methods

2.1 Animal experiment

Male wild-type C57BL/6J mice (8 weeks, 20–25 g) and Nrf2-deficient mice (Nrf2−/−mice; 8 weeks, 20–23 g) were obtained from Jiangsu Huachuang Xinnuo pharmaceutical Technology Company. Mice were housed at 24 ± 2°C in a 12/12 h light/dark cycle with free access to food and water. Wild-type mice were randomized into the sham, HIRI, and HIRI + RTA-408 groups (n = 6 per group). Nrf2−/− mice were also allocated into the HIRI and HIRI + RTA-408 groups (n = 3 per group). HIRI mice models were generated as previously described [19,20]. One day before the hepatic ischemia, mice in the HIRI + RTA-408 group were intraperitoneally injected with 100 μg/kg RTA-408 (MedChemExpress, USA). Mice were anesthetized by intraperitoneal injection of Tribromoethanol (0.2 mL/10 g), followed by laparotomy. The arterial/portal vessels to the cephalad lobes were clamped for 60 min. Then, the clamps were removed for reperfusion for 24 h. Mice in the sham group received the same operation with no occlusion of vessels. Next mice were euthanized and the liver and blood samples were obtained.

  1. Ethical approval: The research related to animal use has been complied with all the relevant national regulations and institutional policies for the care and use of animals, and has been approved by the Ethics Committee of Jiangsu Huachuang Xinnuo Pharmaceutical Technology Company.

2.2 ALT and AST measurement

Mice blood samples were collected from the eye socket and centrifuged for 20 min at 1,000 × g. Serum ALT and AST levels were determined using an ALT kit (ml076532, Shanghai Enzyme-linked Biotechnology Co., Ltd) and AST kit (ml077324, Shanghai Enzyme-linked Biotechnology Co., Ltd) in accordance with the manufacturer’s instructions.

2.3 Hematoxylin and eosin (H&E) staining

The collected mice liver samples were processed with 4% formaldehyde for 24 h, dehydrated, paraffin-embedded, and sliced into sections (4 μm in thickness). Next samples were subject to H&E staining (C0105, Beyotime, Shanghai, China). The histological changes were observed using an OLYMPUS microscope (CKX53). Hepatic injury score was evaluated using the Suzuki’s method [13].

2.4 Immunohistochemistry (IHC)

Primary MPO antibody (ab208670, 1:1,000, abcam) was cultured with mice liver sections overnight at 4°C. Subsequently, the sections were cocultured with the corresponding secondary antibody (ab205718, 1:2,000, abcam) for 60 min at ambient temperature. After washing with tris-buffered saline with Tween-20 (TBST) thrice, a DAB kit (ZLI-9018, Zsbio, China) was used for color development. Finally, the percentage of MPO-positive was analyzed by Image J.

2.5 TdT-mediated dUTP nick-end labeling (TUNEL)

Cell apoptosis in mice liver samples was assessed using an in situ cell death detection kit (HY-K1091, MCE) in accordance with the manufacturer’s protocol. The tissues were dehydrated, incubated with proteinase K, and cultured with TUNEL solution, followed by counterstaining hematoxylin. An OLYMPUS microscope was applied to capture the images in each group. The percentage of TUNEL-positive was analyzed by Image J.

2.6 Western blot

Cytoplasmic and nuclear protein were extracted with a cytoplasmic/nuclear protein enrichment kit (P0027, Biyun Tian, China) following the manufacturer’s protocol. Mice liver samples in each group were treated with lysate buffer (P0013C, Biyun Tian). Then, the protein samples were separated by gel electrophoresis, followed by electro-transfer to the nitrocellulose membranes (Sigma-Aldrich) blocked by 5% nonfat milk, followed by coincubation with anti-Bax (ab182733, 1:2,000, abcam), anti-Bcl-2 (ab182858, 1:2,000, abcam), anti-cleaved caspase-3 (ab214430, 1:5,000, abcam), anti-Nrf2 (A21176,1:1,000, Abclone), anti-Histone H3 (HY-P80166, 1:1,000, MCE), and anti-HO-1 (ab52947, 1:2,000, abcam) overnight at 4°C, with β-actin as the internal control. After rinsing with TBST thrice, the membranes were cultured with the secondary antibodies at ambient temperature for 60 min. Finally, the protein bands were visualized with an enhanced chemiluminescence kit and ImageJ software was applied for protein quantification.

2.7 Malondialdehyde (MDA) and total superoxide dismutase (SOD) measurement

The MDA content and SOD activities were determined using a lipid peroxidation. MDA and SOD levels were measured using the respective assay kits (MDA: A003-1-2, SOD: A003-3-2, Nanjing Jiancheng, China) according to the manufacturer’s protocols.

2.8 Statistical analysis

GraphPad Prism 8.0 software was applied for data analysis. Data are exhibited as mean value ± standard deviation. The statistical significance of multiple-group difference was assessed by one-way analysis of variance. P < 0.05 indicated statistical significance.

3 Results

3.1 RTA-408 attenuates liver injury in HIRI mice

HIRI mice models were generated to elucidate the effects of RTA-408 in vivo. We found that the serum ALT and AST levels increased in the HIRI group were significantly reduced by the administration of RTA-408 (Figure 1a and b). The results of H&E staining showed that mice liver tissues in the HIRI group exhibited significant damage, lobular structure collapses, necrosis, and inflammatory cell infiltration, and the treatment of RTA-408 was revealed to attenuate the liver injury in HIRI close to normal morphology, with the significantly reduced Suzuki’s score in comparison with the HIRI group (Figure 1c and d). Overall, these results indicated that RTA-408 alleviated the liver injury and improved the liver function of HIRI mice.

Figure 1 RTA-408 alleviates liver injury and improves liver function in HIRI mice. Serum (a) and (b) ALT and AST levels in each group, n = 6. (c) and (d) H&E staining and Suzuki’s score for the morphology examination of mice liver samples, n = 3, (×200). ## P < 0.01 vs Sham group, **P < 0.01 vs HIRI group.
Figure 1

RTA-408 alleviates liver injury and improves liver function in HIRI mice. Serum (a) and (b) ALT and AST levels in each group, n = 6. (c) and (d) H&E staining and Suzuki’s score for the morphology examination of mice liver samples, n = 3, (×200). ## P < 0.01 vs Sham group, **P < 0.01 vs HIRI group.

3.2 RTA-408 mitigated the inflammatory response in HIRI mice

The impact of RTA-408 on HIRI-induced inflammatory response was explored by detecting the level of proinflammatory factors in mice liver tissues. The neutrophil infiltration in mice hepatic tissues was then evaluated. The results of IHC reveled that elevation in the number of MPO-positive cells in HIRI group was counteracted by RTA-408 administration (Figure 2a and b).

Figure 2 RTA-408 reduces the HIRI-induced inflammatory reaction, cell apoptosis, and oxidative stress in mice. (a) and (b) The ratio of MPO-positive in mice hepatic tissues were evaluated by IHC, (×200). (c) and (d) MDA content and SOD activities in mice hepatic tissues. (e) and (f) TUNEL staining was conducted to assess the hepatic apoptosis of mice in indicated groups, n = 3, (×200). ## P < 0.01and # P < 0.05 vs Sham group, **P < 0.01 vs HIRI group.
Figure 2

RTA-408 reduces the HIRI-induced inflammatory reaction, cell apoptosis, and oxidative stress in mice. (a) and (b) The ratio of MPO-positive in mice hepatic tissues were evaluated by IHC, (×200). (c) and (d) MDA content and SOD activities in mice hepatic tissues. (e) and (f) TUNEL staining was conducted to assess the hepatic apoptosis of mice in indicated groups, n = 3, (×200). ## P < 0.01and # P < 0.05 vs Sham group, **P < 0.01 vs HIRI group.

3.3 RTA-408 repressed the oxidative stress induced by HIRI in vivo

The effects of RTA-408 on oxidative stress in HIRI mice models were investigated. The MDA content in mice hepatic tissues showed significant elevation while the SOD activities exhibited significant reduction in HIRI mice. The administration of RTA-408 was demonstrated to reverse the HIRI induced changes in oxidative stress markers in the HIRI + RTA-408 group (Figure 2c and d). Collectively, RTA-408 alleviated the HIRI-induced oxidative stress in vivo.

3.4 RTA-408 reduced the liver cell apoptosis in HIRI mice

Whether RTA-408 affected HIRI-induced cell death in mice hepatic tissues was further investigated. As revealed by TUNEL staining, the percentage of TUNEL-positive cells showed an increase in the HIRI group, which was significantly reversed by the administration of RTA-408, suggesting that RTA-408 protected liver cells from apoptosis following HIRI in vivo (Figure 2e and f). Then, we evaluated the protein expression of apoptosis-related proteins in mice liver tissues using western blot. Protein levels of Bax and cleaved caspase-3 increased in the mice hepatic tissues of the HIRI group and Bcl-2 reduced in the HIRI group were rescued by the treatment of RTA-408 (Figure 3a and b). Overall, RTA-408 suppresses the HIRI-induced cell death in mice liver tissues.

Figure 3 RTA-408 reduces the HIRI-induced cell apoptosis in mice liver tissues. (a) and (b) Bax, Bcl-2, and cleaved caspase-3 protein levels in mice liver samples were examined using western blot. RTA-408 activated the Nrf2/HO-1 pathway in vivo. (c) and (d) The protein levels of Nrf2 and HO-1 in mice hepatic tissues were assessed by western blot, n = 3. ## P < 0.01 vs Sham group, **P < 0.01 and *P < 0.05 vs HIRI group.
Figure 3

RTA-408 reduces the HIRI-induced cell apoptosis in mice liver tissues. (a) and (b) Bax, Bcl-2, and cleaved caspase-3 protein levels in mice liver samples were examined using western blot. RTA-408 activated the Nrf2/HO-1 pathway in vivo. (c) and (d) The protein levels of Nrf2 and HO-1 in mice hepatic tissues were assessed by western blot, n = 3. ## P < 0.01 vs Sham group, **P < 0.01 and *P < 0.05 vs HIRI group.

3.5 RTA-408 activated the Nrf2/HO-1 pathway in HIRI mice

We then delved into the potential mechanism of RTA-408 in the process of HIRI, and its effects on the Nrf2/HO-1 pathway was investigated. The administration of RTA-408 was demonstrated to increase the Nrf2 and HO-1 levels in mice liver tissues (Figure 3c and d).

3.6 Effects of RTA-408 on HIRI in Nrf2−/− mice

Whether RTA-408 protected ischemia-reperfusion injury by activating the Nrf2 signaling was further explored. Nrf2 knockout (Nrf2−/−) mice were used to establish HIRI mice models. The administration of RTA-408 showed no significant effects on ALT and AST levels in mice serum relative to the HIRI group (Figure 4a and b). Moreover, H&E staining indicated that the HIRI-induced liver tissue injury was not changed by the RTA-408 treatment in comparison with the HIRI group, and histological score in the two groups showed no significant difference (Figure 4c and d). Overall, RTA-408 protected mice from liver ischemia-reperfusion injury via Nrf2 activation.

Figure 4 The effects of RTA-408 on HIRI in Nrf2−/− mice. Serum (a) ALT and (b) AST levels in Nrf2−/− mice subjected to indicated treatment. (c) and (d) H&E staining and Suzuki’s score for the morphology examination of mice liver samples, n = 3, (×200).
Figure 4

The effects of RTA-408 on HIRI in Nrf2−/− mice. Serum (a) ALT and (b) AST levels in Nrf2−/− mice subjected to indicated treatment. (c) and (d) H&E staining and Suzuki’s score for the morphology examination of mice liver samples, n = 3, (×200).

4 Discussion

HIRI is a common complication and major mechanism of injury following liver transplantation and hepatectomy, which has significantly affected the prognosis of patients [20–22]. The activation of Nrf2 is reported to act as a protective endogenous gene in ischemic injury, with protective effects against oxidative stress damage and HIRI [23,24]. In this study, the impact of RTA-408, a potent Nrf2 activator, on HIRI was explored using the HIRI mice models. As discovered, the administration of RTA-408 significantly improved the liver function and alleviated HIRI, oxidative stress response, inflammation as well as cell apoptosis in mice liver tissues via activating Nrf2.

Oxidative stress is essentially implicated in the regulation of HIRI [3,25]. It can induce apoptotic and necrotic cell death and promote the secretion of proinflammatory factors [23]. Substantial evidence has revealed that Nrf2 activation attenuates oxidative stress in various ischemia-reperfusion injuries [14,26,27]. Therefore, it may be useful for the targeted therapy of ischemia-reperfusion injury [28]. According to our previous study, RTA-408 alleviates oxidative stress and improves kidney function in mice with renal ischemia-reperfusion injury [11]. Liu et al. reported that RTA-408 alleviated oxidative stress damage in retinal pigment epithelial cells by activating the Nrf2 signaling [10]. In our present work, the oxidative stress markers showed significant difference between the HIRI and sham groups. Besides, the HIRI-induced increase in MDA content and reduction in SOD activity were reversed by the administration of RTA-408. Consistently, the elevated expression of inflammatory factors induced by HIRI was restored after RTA-408 treatment. Also, the HIRI-induced apoptosis was reduced by exposure to RTA-408.

Nrf2 is a transcriptional regulator of intracellular antioxidant proteins and is crucially implicated in the redox homeostasis [29]. It can bind to Keap1 in the cytoplasm under the inactivated condition and translocate to the nucleus in response to pathological stimuli such as oxidative stress [30]. HO-1, a phase II detoxifying enzyme, is up-regulated by Nrf2 [31]. It is also highly inducible by various discriminating stimuli that cause hepatic oxidative stress [11]. Both of them serve as the powerful free radical scavengers in the body [32]. In our study, RTA-408 could activate the Nrf2/HO-1 signaling in response to oxidative stress induced by HIRI in mice. Furthermore, we found that RTA-408 did not significantly influence the liver function or levels of oxidative biomarkers in the Nrf2−/− mice, demonstrating that RTA-408 protected from HIRI by activating the Nrf2/HO-1 signaling.

In conclusion, RTA-408 alleviates HIRI by reducing oxidative stress damage and inflammatory responses, and improving liver function in the HIRI mice models. The results of this study can provide evidence for the application of RTA-408 in the treatment of HIRI.

# These authors contributed equally to this work.

Acknowledgments

All authors thank Jiangsu Huachuang Xinuo Medical Technology Co., Ltd. and Xiao Wang for their technical guidance.

  1. Funding information: This study was supported by the Fengcheng Talent Plan Youth Science and Technology Talent Recruitment Project of Taizhou (Grant 202210); the Research Foundation of Taizhou People’s Hospital (Grant ZL202210); Jiangsu Research Hospital Association for Precision Medication (JY202229); and Taizhou Science and Technology Support Plan (Social Development) Project (Project number: TS202414).

  2. Author contributions: JW, JDL, and SJ designed the research; YQ, ZQL, and BP performed the experiments; HLH and JW the analyzed data; HLH and JDL wrote the manuscript; ZQL, BP, and SJ provided valuable comments and helped to revise the manuscript. All authors reviewed the final version and agreed to its submission. All authors have read and agreed to the published version of the manuscript.

  3. Conflict of interest: Jiangsu Huachuang Xinnuo Pharmaceutical Technology Company provided facilities for animal testing, which has been performed by the Authors of this study. The company was not involved in manuscript writing and has not influenced the obtained results. Authors state no conflict of interest between The Affiliated Taizhou People s Hospital of Nanjing Medical University and Jiangsu Huachuang Xinnuo Pharmaceutical Technology Company.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2024-10-10
Revised: 2025-02-27
Accepted: 2025-03-10
Published Online: 2025-04-24

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Biomedical Sciences
  2. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  3. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  4. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  5. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  6. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  7. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
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  9. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
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  12. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  13. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  14. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  15. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  16. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  17. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  18. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  19. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  20. Changes in blood glucose and metabolism in hyperuricemia mice
  21. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  22. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  23. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  24. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  25. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  26. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
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  28. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
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  35. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  36. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  37. Low-pressure exposure influences the development of HAPE
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  39. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
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  199. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
  200. Retraction
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https://doi.org/10.1515/biol-2025-1093
Keywords for this article
RTA-408; Nrf2; HO-1; oxidative stress; hepatic ischemia reperfusion injury
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  3. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  4. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  5. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  6. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  7. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  8. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
  9. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
  10. Battling COVID-19 leveraging nanobiotechnology: Gold and silver nanoparticle–B-escin conjugates as SARS-CoV-2 inhibitors
  11. Neurodegenerative diseases and neuroinflammation-induced apoptosis
  12. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  13. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  14. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  15. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  16. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  17. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  18. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  19. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  20. Changes in blood glucose and metabolism in hyperuricemia mice
  21. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  22. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  23. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  24. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  25. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  26. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  27. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  28. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  29. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  30. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  31. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  32. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  33. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  34. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  35. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  36. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  37. Low-pressure exposure influences the development of HAPE
  38. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  39. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  40. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  41. A case of bloodstream infection caused by Neisseria gonorrhoeae
  42. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  43. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  44. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  45. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  46. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  47. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  48. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  49. Sodium butyrate aids brain injury repair in neonatal rats
  50. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  51. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  52. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  53. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  54. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  55. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  56. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  57. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  58. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  59. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  60. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  61. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  62. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  63. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  64. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  65. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  66. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  67. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  68. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  69. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  70. Oncolytic bacteria: A revolutionary approach to cancer therapy
  71. A de novo meningioma with rapid growth: A possible malignancy imposter?
  72. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  73. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  74. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  75. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  76. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  77. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  78. Evaluation and application analysis of animal models of PIPNP based on data mining
  79. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  80. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  81. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  82. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  83. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  84. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  85. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  86. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  87. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  88. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  89. RNF144A and RNF144B: Important molecules for health
  90. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  91. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  92. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  93. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  94. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  95. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  96. Understanding risk factors and prognosis in diabetic foot ulcers
  97. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  98. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  99. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  100. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  101. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  102. Pulmonary cryptococcosis with headache as the first presentation: A case report
  103. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  104. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  105. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  106. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  107. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  108. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  109. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  110. Wound healing and signaling pathways
  111. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  112. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  113. Research progress on the impact of curcumin on immune responses in breast cancer
  114. Biogenic Cu/Ni nanotherapeutics from Descurainia sophia (L.) Webb ex Prantl seeds for the treatment of lung cancer
  115. Dapagliflozin attenuates atrial fibrosis via the HMGB1/RAGE pathway in atrial fibrillation rats
  116. Glycitein alleviates inflammation and apoptosis in keratinocytes via ROS-associated PI3K–Akt signalling pathway
  117. ADH5 inhibits proliferation but promotes EMT in non-small cell lung cancer cell through activating Smad2/Smad3
  118. Apoptotic efficacies of AgNPs formulated by Syzygium aromaticum leaf extract on 32D-FLT3-ITD human leukemia cell line with PI3K/AKT/mTOR signaling pathway
  119. Novel cuproptosis-related genes C1QBP and PFKP identified as prognostic and therapeutic targets in lung adenocarcinoma
  120. Bee venom promotes exosome secretion and alters miRNA cargo in T cells
  121. Treatment of pure red cell aplasia in a chronic kidney disease patient with roxadustat: A case report
  122. Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status
  123. Kynurenine facilitates renal cell carcinoma progression by suppressing M2 macrophage pyroptosis through inhibition of CASP1 cleavage
  124. RFX5 promotes the growth, motility, and inhibits apoptosis of gastric adenocarcinoma cells through the SIRT1/AMPK axis
  125. ALKBH5 exacerbates early cardiac damage after radiotherapy for breast cancer via m6A demethylation of TLR4
  126. Phytochemicals of Roman chamomile: Antioxidant, anti-aging, and whitening activities of distillation residues
  127. Circadian gene Cry1 inhibits the tumorigenicity of hepatocellular carcinoma by the BAX/BCL2-mediated apoptosis pathway
  128. The TNFR-RIPK1/RIPK3 signalling pathway mediates the effect of lanthanum on necroptosis of nerve cells
  129. Longitudinal monitoring of autoantibody dynamics in patients with early-stage non-small-cell lung cancer undergoing surgery
  130. The potential role of rutin, a flavonoid, in the management of cancer through modulation of cell signaling pathways
  131. Construction of pectinase gene engineering microbe and its application in tobacco sheets
  132. Construction of a microbial abundance prognostic scoring model based on intratumoral microbial data for predicting the prognosis of lung squamous cell carcinoma
  133. Sepsis complicated by haemophagocytic lymphohistiocytosis triggered by methicillin-resistant Staphylococcus aureus and human herpesvirus 8 in an immunocompromised elderly patient: A case report
  134. Sarcopenia in liver transplantation: A comprehensive bibliometric study of current research trends and future directions
  135. Advances in cancer immunotherapy and future directions in personalized medicine
  136. Can coronavirus disease 2019 affect male fertility or cause spontaneous abortion? A two-sample Mendelian randomization analysis
  137. Heat stroke associated with novel leukaemia inhibitory factor receptor gene variant in a Chinese infant
  138. PSME2 exacerbates ulcerative colitis by disrupting intestinal barrier function and promoting autophagy-dependent inflammation
  139. Hyperosmolar hyperglycemic state with severe hypernatremia coexisting with central diabetes insipidus: A case report and literature review
  140. Efficacy and mechanism of escin in improving the tissue microenvironment of blood vessel walls via anti-inflammatory and anticoagulant effects: Implications for clinical practice
  141. Merkel cell carcinoma: Clinicopathological analysis of three patients and literature review
  142. Genetic variants in VWF exon 26 and their implications for type 1 Von Willebrand disease in a Saudi Arabian population
  143. Lipoxin A4 improves myocardial ischemia/reperfusion injury through the Notch1-Nrf2 signaling pathway
  144. High levels of EPHB2 expression predict a poor prognosis and promote tumor progression in endometrial cancer
  145. Knockdown of SHP-2 delays renal tubular epithelial cell injury in diabetic nephropathy by inhibiting NLRP3 inflammasome-mediated pyroptosis
  146. Exploring the toxicity mechanisms and detoxification methods of Rhizoma Paridis
  147. Concomitant gastric carcinoma and primary hepatic angiosarcoma in a patient: A case report
  148. Ecology and Environmental Science
  149. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  150. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  151. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  152. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  153. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  154. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  155. Global assessment of the fate of nitrogen deposition in forest ecosystems: Insights from 15N tracer studies
  156. Fungal and bacterial pathogenic co-infections mainly lead to the assembly of microbial community in tobacco stems
  157. Influencing of coal industry related airborne particulate matter on ocular surface tear film injury and inflammatory factor expression in Sprague-Dawley rats
  158. Temperature-dependent development, predation, and life table of Sphaerophoria macrogaster (Thomson) (Diptera: Syrphidae) feeding on Myzus persicae (Sulzer) (Homoptera: Aphididae)
  159. Eleonora’s falcon trophic interactions with insects within its breeding range: A systematic review
  160. Agriculture
  161. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  162. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  163. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  164. Molecular mechanism of follicular development in laying hens based on the regulation of water metabolism
  165. Animal Science
  166. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  167. Plant Sciences
  168. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  169. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  170. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  171. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  172. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  173. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  174. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  175. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  176. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  177. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  178. Using plant electrical signals of water hyacinth (Eichhornia crassipes) for water pollution monitoring
  179. Food Science
  180. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  181. Review on role of honey in disease prevention and treatment through modulation of biological activities
  182. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  183. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  184. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  185. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  186. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  187. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  188. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  189. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  190. The dilemma of food genetics and improvement
  191. Bioengineering and Biotechnology
  192. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  193. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  194. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  195. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  196. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  197. Corrigendum
  198. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  199. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
  200. Retraction
  201. Retraction of “Down-regulation of miR-539 indicates poor prognosis in patients with pancreatic cancer”
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