This study investigates the role of TNF receptors-associated factors 6 (TRAF6) in 5-Fluorouracil (5-FU) resistant GC...Importantly, TRAF6, an E3 ubiquitin ligase, bound to the IRF3-Δ (SR + IAD) (1-190aa) domain, inducing Lys70 ubiquitination of IRF3 to regulate its protein stability, with ubiquitin K48 residue playing a crucial role in this process. In conclusion, our study reveals the mechanism by which the TRAF6/IRF3 axis decreases GC's cells sensitivity to 5-FU by promoting nuclear translocation of NF-κB-p65, offering valuable insights into overcoming chemoresistance in GC.

CRNDE alleviated IL-1β-induced injuries in OA chondrocytes by suppressing the miR-31-mediated NF-κB signaling pathway.

BAY11-7082, which is an inhibitor of the inhibitor of nuclear factor κB protein α(IκBα), was used to explore the effect of the expression of phosphorylated nuclear factor κB(p-NF-κB) in the nucleus after the Fur treatment on the NOX4 protein level...In the stably transfected cell strain with PRDX1 gene knockout, the apoptosis rate is considerably higher than that of the negative control group after Fur treatment. The above results indicate that Fur can induce the apoptosis of colorectal cancer cells by promoting the signal transduction of NF-κB in the nucleus and increasing the generation of mitochondrial ROS derived from NOX4 to inhibit the PRDX1 protein expression.

CEP70 promotes tumour angiogenesis and metastasis by upregulating VEGFA through NF-κB pathway activation.

Notably, CDDO-Me attenuates TNBC progression by accelerating EGFR degradation in cell-derived xenografts and patient-derived organoid models, highlighting its clinical application potential. Consequently, induction of EGFR degradation through MG degraders represents a viable therapeutic strategy for TNBC.

The network pharmacology data suggested that TP may inhibit glioma proliferation by regulating the signaling pathway of the nuclear factor kappa-B (NF-κB). The results showed that the underlying mechanism involved the regulation of the NF-κB signaling pathway to promote the generation of reactive oxygen species, thereby enhancing oxidative stress response and promoting cell apoptosis.

P1, N=9, Withdrawn, Flinders University | Recruiting --> Withdrawn

We previously identified SBI-756, a small molecule that interferes with the eIF4F assembly and overcomes melanoma resistance to BRAF inhibitors...Alone, M19-6 reduced melanoma growth and metastasis in a xenograft model. M19-6 offers a new therapeutic modality to overcome resistance and metastasis.

Further, Autophagy inhibits S. suis infection-induced NF-κB and MAPK signaling and subsequent inflammatory factors CCL2, CCL3, CCL5, and TNF-α. Collectively, these findings suggest that AMPK/mTOR-regulated autophagy has an inhibitory effect on pro-inflammatory cytokines and chemokines by regulating the NF-κB and MAPK pathways.

Our findings verify the therapeutic effects of targeting LIF in SFN-resistance, uncover the potential mechanism for the increased sensitivity to SFN and sought to elucidate how this intervention might contribute to overcoming SFN resistance. KLTI is a promising immunomodulatory drug by regulating LIF and macrophage-NK cell interaction, which could be a potential combination partner for HCC treatment.

Altogether, these data suggest that NF-κB may be a potential therapeutic target for pharmacological interventions for depression.

Using letrozole and a high-fat diet, a PCOS rat model was established, along with a Lipopolysaccharide (LPS) -treated KGN cell inflammation model was established. NF-κB and TERT inhibitors (BAY 11-7082 and BIBR1532) were then administered to LPS-induced KGN cells...LPS-treated KGN cells demonstrated increased expression of inflammatory and pro-apoptotic factors, later restored post-treatment with NF-κB and TERT inhibitors (P are all less than 0.05). In conclusion, TERT may induce granulosa cell apoptosis by participating in the regulation of the NF-κB signaling pathway, thereby mediating the chronic inflammatory response of PCOS through downstream inflammatory factors IL-6 and TNF-α.

In addition to activating NF-κB, the NF-κB inhibitor BAY 11-7082 reduced skatole-induced cell survival and the mRNA expression of IL-6 and TNF-α. NF-κB activation was attenuated by the extracellular signal-regulated kinase (ERK) pathway inhibitor U0126 and the p38 inhibitor SB203580, but not by the c-Jun N-terminal kinase (JNK) inhibitor SP600125...Moreover, the balance between NF-κB and AhR activation appears to govern the skatole-induced increases in IL-6 and TNF-α expression. Therefore, the present findings provide new insights into the mechanisms linking tryptophan-derived gut microbiota metabolites with colorectal disease.

These results, obtained in vitro, were corroborated on 3D systems made up of Poly-L-Lactic Acid (PLLA) scaffolds. In summary, SEMBL exerts interesting anti-tumor activities in preclinical breast cancer models and therefore it could be a promising new molecule to be studied also in other types of neoplastic disease.

These results suggest that OE and oleandrin are efficacious agents to treat canine atopic dermatitis. Future studies should evaluate the efficacy of these compounds in dogs affected by atopic dermatitis.

HSP70 promotes the EMT and enhances pancreatic cancer cell proliferation, migration, and invasion by activating the NF-κB pathway.

The transcriptomics sequencing and real-time qPCR indicated that Altechromone A inhibited the expression of pro-inflammatory genes including TNF-α, NF-κB, IL-1, IL-1β, IL-6, and NLRP3. Therefore, these data indicate that Altechromone A exhibits therapeutic effects in IBD by inhibiting the inflammatory response.

P1/2, N=52, Active, not recruiting, Golden Biotechnology Corporation | Trial completion date: Mar 2024 --> Dec 2024

In summary, our findings suggest that bufalin exerts anti-inflammatory and antioxidant actions in NaT-SAP rats by inhibiting NF-κB and activating the Keap1-Nrf2/HO-1 pathway. This study represents the inaugural application of bufalin in NaT-induced SAP rats, indicating its potential as an effective therapeutic agent for SAP patients.

Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells.

Lacidipine demonstrated a protective effect in UC, reducing inflammation and modulating key signaling pathways. These findings suggest that lacidipine could be a promising candidate for the treatment of UC.

Our findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.

Human neuroblastoma M1C cells harboring wild-type tau (4R0N) were used with the tetracycline off (TetOff) induction system. In this model of neuronal tauopathy, the effects of the Syk inhibitors-BAY 61-3606 and R406-on tau phosphorylation and oligomerization were explored using several phosphorylated tau-specific antibodies and an oligomeric tau antibody, and the effects of these Syk inhibitors on autophagy were examined using western blot analyses...In vivo, the Syk inhibitor R406 decreased phosphorylated tau levels in wild-type mice. These findings suggest that Syk inhibitors offer novel therapeutic strategies for tauopathies, including AD.

SMAD2 and NF-κB p65 were overexpressed and transfected into cells, and the inhibitors SB431542 and BAY 11-7082 were added to block the TGF-β1/Smad and NF-κB pathways, respectively...BBR can significantly inhibit TGF-β1-induced EMT in normal and cancerous colon epithelial cells through the inhibition of the TGF-β1/Smad and NF-κB p65 pathways. TGF-β1/Smads can promote the NF-κB p65 pathway, which is a common target of miR-1269a, and can partially regulate the expression of miR-1269a.

It concluded that mitochondria-derived ROS mediated differentiation of PECs into podocytes via Nrf2 and Brg1 signaling.

Our study uncovered a novel pathway in platelet activation involving the cPLA2-NF-κB axis, which plays a key role in the antiplatelet effects of eugenol. These findings suggest that eugenol could serve as a valuable and potent prophylactic or therapeutic option for arterial thrombosis.

In vitro, baicalin demonstrates anti-OS effects and facilitates osteogenic differentiation, potentially by inhibiting NF-κB pathway activity.

Our observations suggest that SOX9 expression may serve as a putative indicator of TO formation, indicating a critical role of Sertoli cells in promoting organoid formation, seminiferous tubule integrity, and testicular function in pre- and peri-pubertal testicular tissue.

P2, N=132, Active, not recruiting, GeneOne Life Science, Inc. | Trial completion date: Dec 2023 --> Dec 2024

The inflammatory responses were reversed by NLRP3 inhibitor MCC950 and NF-κB inhibitor Bay11-7082. Additionally, N-acetylcysteine (NAC) blocked the upregulation of the NF-κB/NLRP3 signaling pathway and remarkably alleviated the inflammatory response. These results demonstrated that AMA could induce inflammation through activating the NLRP3 inflammasome triggered by ROS/NF-κB signaling pathway. Our research provides new insights into the molecular mechanism of AMA-induced inflammation damage and may contribute to establish new prevention strategies for AMA hepatotoxicity.

The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.

Induction of hepatic Nrf1 activity with hNRF1 enhanced the effect of bardoxolone on steatosis and may have stimulated liver progenitor cells. Physiologic Nrf1 delays MASLD progression, Nrf2 induction alleviates MASH, and combined enhancement synergistically protects against steatosis and may facilitate liver repair.

Taken together, our data indicate that GP-2250 exerts profound effects on tumor metabolism and, in combination with PARP inhibitors or bevacizumab, showed promising anti-tumor efficacy. These findings could have implications for the clinical development of GP-2250.

These findings suggest that Nes-1 might be used as a promising agent for the prevention of CA.

P3/4, N=120, Completed, Menzies School of Health Research | Recruiting --> Completed

Our results indicate that in this study NE3107 was associated with what appear to be positive neurophysiological and neuropsychological findings, as well as evidence of improvement in biomarkers associated with neuroinflammation and AD in patients diagnosed with dementia. Our findings are consistent with previous preclinical and clinical observations and highlight a central role of neuroinflammation in AD pathogenesis.

Further investigations revealed that the KATP channel inhibitor 5-HD upregulated p-NF-κB p65, NF-κB p65, and p-IκBα expression, promoting microglial cell activation, pyroptosis, and inflammatory factor secretion, attenuating Nicorandil's neuroprotective effect in vivo. Overall, our results suggest that opening KATP channels can improve post-ischemic neurological function by inhibiting AIM2 inflammasome-induced microglial pyroptosis and NF-κB/IκBα signaling activation.

These analyses define a core NRF2 gene signature that is robust, versatile, and useful for evaluating NRF2 activity and for predicting drug resistance and cancer prognosis. Using this gene signature, we uncover novel selective drug resistance and cancer prognosis associated with NRF2 activation.

P2, N=5, Recruiting, Neurological Associates of West Los Angeles | Not yet recruiting --> Recruiting | Phase classification: P2a --> P2 | Trial completion date: Jul 2024 --> Jul 2025 | Initiation date: Aug 2023 --> Dec 2023 | Trial primary completion date: Jun 2024 --> Dec 2024

Ki67, CCND1, and E2F1 expression decreased with Bay treatment. This preclinical study suggests NF-kB inhibition as an effective fibroid treatment, suppressing genes involved in proliferation, inflammation, and ECM remodeling.

Our study identifies BAY 11-7082 to be an efficacious inhibitor for treating RAS oncogene (HRAS, KRAS, and NRAS) mutant cancer cells. This finding provides new therapeutic opportunity for effective treatment of RAS-mutant cancers.

Pharmacological inhibition of Hippo/MST1/2 blocked NF-κB transcriptional program and suppressed ccRCC cancer cell growth, which can be rescued by ZHX2/p65 overexpression. Our study uncovers a novel crosstalk between the Hippo and NF-κB pathways and its involvement in ccRCC growth inhibition, suggesting that targeting the Hippo pathway may provide a therapeutical opportunity for ccRCC treatment.