KEAP1 expression

The ABC subtype was also associated with lower white blood cell counts and more frequent chemotherapy courses than the GCB subtype. These findings suggest that nuclear Nrf2 could be a biomarker for DLBCL clinical diagnosis.

To sum up, the present research indicated that DBH can ameliorate D-gal-induced oxidative stress and apoptosis by regulating the Nrf2/HO-1 signalling pathway and the Bcl-2/Bax/caspase-3 apoptosis pathway, which can be used for further development as a nutraceutical product to improve premature ovarian failure.

Furthermore, the growth rate of CRC tumors was associated with alterations in the levels of oxidative stress enzymes and Keap1 expression in animals with a high metabolic rate. Our results indicate that a faster growth and development of CRC line DLD-1 is associated with enzymatic redox imbalance in animals with a high BMR.

Inhibition of miR-141-3p promoted Keap1 expression, inhibited Nrf2 and its downstream SLC7A11-GSH-GPX4 signaling pathway, as well as promoted ferroptosis in cancer cells, and inhibited paclitaxel and RSL3 resistance. In vivo, miR-141-3p mimics promoted paclitaxel resistance, whereas miR-141-3p inhibitors inhibited paclitaxel resistance in breast cancer cells. This work revealed that modulation of the Keap1-Nrf2 signaling pathway by miR-141-3p promoted paclitaxel resistance via regulating ferroptosis in breast cancer cells.

These result suggest that maternal TFA exposure during gestation can result in oxidative stress and inflammation to brain of offspring in a way. SDG can protect brain of mice of offspring from TFA-induced oxidative injury by up-regulating the expression of mRNA and protein of Nrf2, down-regulating the expression of Keap1, accelerating expression of protein of NQO1 and HO-1 which are antioxidant protein lying downstream of pathway of Nrf2/Keap1.

Besides, PQ exposure prompted various histopathological damages in renal tissues. Nonetheless, SCN substantially restored aforementioned alterations in renal tissues owing to its anti-oxidative, anti-inflammatory and anti-apoptotic potential.

These findings demonstrate the inhibitory effects and associated mechanisms of AAVC-I on the HSC-3 OSCC cell line. This insight could be valuable for investigating AAVC-I as a potential therapeutic option for patients with OSCC.

Taken together, GF2 ameliorated MI by preventing cardiocyte apoptosis, oxidative stress, and mitochondrial dysfunction via modulating the Nrf2/HO-1 and PI3K/Akt signaling pathways, showing potential as a treatment strategy for treating MI.

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.