KEAP1 expression

ERCN treatment remarkably ameliorated the hepatic tissues owing to its antioxidant, anti-inflammatory, and anti-apoptotic potentials. These findings underscore the therapeutic potential of ERCN to counteract the adverse effects of environmental pollutants on hepatic tissues.

Mitochondrial dysfunction manifested with diminished activities of Krebs cycle and respiratory chain enzymes, and reduced mitochondrial membrane potential. Co-treatment with hyperin significantly attenuated these detrimental effects through its anti-apoptotic, antioxidant, and anti-inflammatory properties. Hyperin co-treatment significantly attenuated CdCl2-induced renal damage in mice, suggesting its potential as a protective agent against cadmium-induced kidney toxicity.

Background: KRAS G12C inhibitors (G12Ci) are revolutionizing the therapeutic landscape of advanced NSCLC, but mechanisms of limited clinical efficacy observed in some patients (pts) merit continued exploration. Co-mutations in KEAP1 and STK11 and NRF2 signaling define a subgroup of KG12C NSCLC pts with markedly distinct outcomes upon treatment with ada. The mTORi and ada combination shows high efficacy for targeting KG12C NSCLC harboring KEAP1 and STK11 co-mutations. The clinical safety and efficacy of mTORi nab-sirolimus and ada will be determined in the ongoing KRYSTAL-19 trial (NCT05840510).

In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.

The low-expressed LncRNA DANCR may regulate the Keap1-Nrf2/ARE pathway and suppress the inflammatory and oxidative responses in RA patients.

However, didymin supplementation ameliorated all the PS-NPs-induced damage in the liver of rats. Therefore, it was concluded that didymin can act as a remedy against PS-NPs-induced liver toxicity due to its anti-apoptotic, anti-oxidant, and anti-inflammatory activities.

The findings indicate that Rg1 significantly ameliorates chronic liver damage and fibrosis induced by LPS. The mechanism may be mediated through promoting the dissociation of Nrf2 from Keap1 and then activating Nrf2 signaling and further inhibiting NLRP3, NLRP1, and AIM2 inflammasomes in liver cells.

However, the co-administration of AMF significantly improved the abovementioned hepatic damages induced by PQ. The present study indicated that AMF may be an effective therapeutic candidate to mitigate PQ provoked hepatic impairments due to its anti-apoptotic, antioxidant & anti-inflammatory properties.

Further, molecular studies confirmed the changes in Nrf2 and Keap1 expression during SIRT6 inhibition. The overall study suggests that SIRT6 inhibition by imidazole derivative disrupts Nrf2/Keap1 signaling leading to oxidative stress and apoptosis induction.

After the optimal extraction of total flavonoids from the stems and leaves of Epimedium, the molecular docking technique combined with animal experiments suggested that the effective component of the total flavonoids of Epimedium might activate the Keap1-Nrf2 signaling pathway after treatment to reduce the inflammation and oxidative stress of kidney tissue, so as to reduce kidney damage and improve kidney function. Therefore, EBF may become a new natural protective agent for CTX chemotherapy in the future.

Notably, RES prevented UC-like pathology and depressive-like behavior and enhancement of autophagy, decreased rectal and hippocampal inflammatory cytokines and inflammasome, and induced the Nrf2-PGC1α-SOD1 pathway in the hippocampus, resulting in neurogenesis in the hippocampal dentate gyrus. Our findings suggest that brain-gut AMPK activation may be an important therapeutic strategy in patients with UC and depression.

In conclusion, our results suggest that palmatine may have a potential therapeutic effect on AD and could be further investigated as a promising therapeutic agent for AD. It provides a theoretical basis for the development of related drugs.

In addition, ICS II had a strong binding with Keap1 and Nrf2 inhibitor ML385 partially abolished the suppressive role of ICS II in MPP-triggered apoptosis, oxidative stress, and ferroptosis in SK-N-SH cells. To summarize, ICS II might inhibit apoptosis, oxidative stress, and ferroptosis in the MPP-stimulated PD cell model, which might be due to the activation of Keap1/Nrf2/GPX4 signaling.

Higher expression of MnSOD in patients with endometrial cancer and T2DM is associated with better overall survival if the patient is consuming metformin.

Nevertheless, KFD supplementation significantly (P < 0.05) abrogated all the damages induced by PE-MPs. The findings of our study demonstrated that KFD could significantly attenuate PE-MPs-instigated OS and testicular toxicity, due to its anti-oxidant, anti-inflammatory, androgenic and anti-apoptotic potential.

However, TMT treatment substantially (p < .05) recovered all the PS-MPs-induced damages and histopathological changes. Taken together, it can be deduced that TMT might be used as a pharmacological agent to ameliorate hepatic damage.

The protective effect of DN on neurocytes have been demonstrated in both in vitro and in vivo circumstances. It deserves to be developed as a potential neuroprotective agent through regulating the Nrf2/HO-1 signaling pathway to ameliorate neurocytes impairment caused by OS.

High NRF2 and low KEAP1 expressions independently predicted poor survival in patients with operable TNBC. Further investigations are warranted to examine the possible therapeutic benefits of targeting the KEAP1-NRF2 pathway for TNBC treatment.

Nuclear translocation of NRF2 was correlated with the magnitude of liver inflammation and fibrosis in chronic liver disease. These results suggest that NRF2 plays a protective role in the development of chronic liver diseases such as NASH and CHc.

Taken together, our study recognizes that NRF2-dependent redox control is regulated by the SUMOylation of KEAP1. These findings identify a potential new therapeutic option to counteract oxidative stress.

H460 KEAP1/STK11 mutant cell line derived xenograft model was used to demonstrate the anti-tumor activity of LP-184. LP-184 displayed strong nanomolar potency in 7 day ex vivo treatment in a panel of patient derived lung cancer models carrying ATM, BRCA1 or CHEK1 mutations with IC50s in the range of 30 - 200 nM, which turned out to be 12-350 times superior to that of Olaparib across the same models. LP-184 is highly effective in selected molecular subsets of lung cancer in proof-of-concept ex vivo and in vivo studies, supporting its clinical development in small cell and non-small cell lung cancers. IND-enabling repeat dose GLP toxicology studies of LP-184 show it to be well tolerated in rats and dogs. A first-in-human dose escalation Phase 1A trial with LP-184 is expected to enroll all advanced solid tumors including lung cancers.

This study suggests that Nrf2 overexpression reduces the efficacy of adjuvant chemotherapy in distal cholangiocarcinoma.

CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance. The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

Collectively, miR-141-3p contributes to tumor progression, migration, and M2 polarization of OC by activating the Keap1-Nrf2 pathway. Inhibition of miR-141-3p attenuates the malignant biological behavior of ovarian cells by inactivating the Keap1-Nrf2 pathway.

Finally, NRF2 overexpression in KEAP1 mutant human NSCLC cell lines was detrimental to cell proliferation, viability, and anchorage-independent colony formation. Collectively, these results establish the context-dependence and activity threshold for NRF2 during the lung tumorigenic process.

A virtual screen showed that etoposide and eltrombopag could bind to KEAP1 and potentially interact with ATO. KEAP1 is the most critical gene regulating ATO drug sensitivity, which is related to AML prognosis and may bind to some clinical drugs leading to an interaction with ATO. These integrated results provided new insights into the pharmacological mechanism of ATO and potentiate for further applications in cancer treatments.

Moreover, CPW pretreatment significantly regulated the expression of Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-associated genes (Keap1, Nrf2, NADPH quinone oxidoreductase I (NQO1), and heme oxygenase-1 (HO-1)) and its downstream antioxidant genes (SOD, CAT, GSH, and the glutamate-cysteine ligase catalytic (GCLC) subunit) in HepG2 cells. These data demonstrated that CPW prevented HO-induced oxidative stress by regulating the Keap1/Nrf2 signaling pathway.

Our results suggest that BRU could be a potential pharmacological agent for the therapeutic approach of CLL, in monotherapy and as an adjuvant to treatment with IBR. Chronic lymphocytic leukemia, Apoptosis, ibrutinib, Transcription factor

Kynu overexpression, coordinate with Nrf2 pathway activation, is a novel mechanism leading to tumor immunomodulation with a T-cell suppressive phenotype including Treg infiltration and expression of immune checkpoints. This immune signature may indicate that these tumors could show a brisk response to immune checkpoint inhibition.

Our results suggest that GSTM4 may play a role in ameliorating the progression of endometriosis. NBDHEX may have therapeutic potential in the treatment of endometriosis.

In conclusion, our data indicate that blood-borne exosomal hsa-piR-1089 is a diagnostic marker for NB and assessing metastasis. Our study provides a quick, simple, and noninvasive diagnostic method for NB and contributes to developing new treatment strategies.

These results collectively establish UBR7 as a critical negative regulator of aerobic glycolysis and HCC tumorigenesis through regulation of the Keap1/Nrf2/Bach1/HK2 axis, providing a potential clinical and therapeutic target for the HCC treatment.

Ectopic expression of Keap1 increased the volume of delaminated follicle cells that showed enhanced invasive behavior with significant changes to the cytoskeleton. Overall, our findings describe the comprehensive transcriptome of cells within the follicle-cell tumor model at the single-cell resolution and identify a previously unappreciated link between Keap1-Nrf2 signaling and cell plasticity at early tumorigenesis.

We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

Such functions were further determined by multiple experiments in vivo (i.e., subcutaneous tumour formation in nude mice) and in vitro (e.g., cell cloning, infection, migration, wound healing, cell cycle, apoptosis, CAT enzymatic activity, and intracellular GSH levels). Of note, the results obtained from tumourigenesis experiments in xenograft model mice were verified based on the prominent changes in the PTEN signaling to the PI3K-AKT-mTOR pathways, in addition to substantially aberrant expression patterns of those typical genes involved in the EMT (epithelial-mesenchymal transition), cell cycle, and apoptosis.

The antitumor effect of CORM-3 was used to xenograft tumor in nude mice for further investigation in vivo, and the result showed that CORM-3 significantly suppressed tumor growth in xenograft nude mice. These data suggest that CORM-3 acts as a tumor suppressor by regulating the Keap1/Nrf2/HO-1 signaling pathway in TSCC, which provides a potential chemotherapeutic strategy for TSCC.

Constitutive NRF2 activation promotes the selective elimination of epithelial cells via cell competition, but this competition induces DNA damage in neighboring KEAP1-normal cells, which predisposes them to chemical-induced ESCC.

Nevertheless, insignificant difference was observed when clinicopathological characteristics were compared with cAMP response element-binding protein-2 expression. These findings suggest that ALD, Keap-1, and FoxO4 reinvolved in CRC development, and thus may be considered as potential monitoring protein for CRC.

B regulates KEAP1/NRF2 signaling, drives metabolic rewiring, CpG methylomic, and transcriptomic reprogramming contributing to the overall cancer-prevention/anticancer effect in the CRC cell model.

Consequently, Withaferin A may attenuate the metastatic potential and sorafenib resistance by regulating Keap1/Nrf2-associated EMT and ferroptosis. Thus, Withaferin A may serve as a promising agent for HCC therapy, especially for advanced HCC.

We showed that miR-200a exerts its effects through its interaction with Keap1, thus altering the Keap1/Nrf2 signaling pathway. Our results suggest that exosome-shuttled miR-200a might be useful as a biomarker for prognosis in patients with ESCC.

Alloimperatorin significantly inhibited the invasion of breast cancer cells, while Keap1 siRNA or GPX4 overexpression vectors significantly enhanced cell invasion and effectively reversed the anti-invasive effect of alloimperatorin. Therefore, alloimperatorin induces breast cancer cell apoptosis, ferroptosis and oxeiptosis, thereby inhibiting cell growth and invasion.