ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1)

Our histological results showed that BSFL extract (360 mg/kg) could reduce steatosis, cellular swelling, and lobular inflammation induced after AF exposure. The results of this study indicate that BSFL extract, as a valuable bioactive substance with antioxidant properties, may attenuate biochemical indices, oxidative stress, and inflammation caused by AF-induced hepatotoxicity.

Notably, co-treatment with chloroquine, an autophagy inhibitor, partially rescued cell viability, underscoring that autophagy contributes to PBE-induced cell death. In addition, PBE modulated several critical signaling pathways by inhibiting EGFR, mTOR, and STAT3 while concurrently activating downstream ERK and the AMPK-ACC axis. Collectively, these results reveal that PBE triggers ER stress-mediated UPR and autophagy to promote autophagic cell death in CRC, supporting its potential development as a novel therapeutic agent for colorectal cancer.

Our findings highlight the beneficial role of TGP in preserving synaptic structural integrity and functionality and suggest a novel mechanism of synaptic dysfunction implicated in the pathophysiology of PSD. The results indicate that the regulation of the ERS signaling pathway by TGP presents therapeutic promise for the treatment of PSD.

Pharmacokinetic parameters indicate that α-mangostin is well tolerated and safe in both preclinical and human clinical trials. In summary, understanding the mechanism of action and identifying direct molecular target of α-mangostin is important for development of novel anti-cancer agents and further clinical studies are required to evaluate its efficacy in chemotherapy.

Inhibition of IRE1 with GSK2850163 suppressed these responses, whereas IRE1 activation with IXA4 reproduced the effects of BvrR. Findings indicate that BvrR from B. abortus activates IRE1, which subsequently stimulates ATF2 and NF-κB p65, leading to increased expression of IL-6 and TNF-α and the induction of inflammatory responses in HMC3 cells.

Crucially, s155 was required for DA-induced PD-L1 suppression in MDA-MB-231 cells. These findings demonstrate PD-L1 as a direct transcriptional target of FoxO3a and identify DA as a potential TNBC therapeutic targeting the IRE1/IKK/FoxO3a/PD-L1 axis.

Nuclear localization of Cyclin B1 increased significantly in TNFα treated hASM cells consistent with the formation of Cyclin B1/CDKs complexes, and increased cell proliferation. Inhibition of pIRE1αS724/XBP1s pathway mitigated TNFα induced Cyclin B1 and CDKs expression and hASM cell proliferation.

MAMs were isolated from NCI-H295S cells treated with mitotane, the ferroptosis inducer RSL3, or control. In conclusion, locally reduced Q10 in MAM may contribute to impaired respiratory chain activity and free radical excess induced by mitotane. Recruitment of GRIPAP1 protein to MAMs may transduce cell death.

Moreover, KIRA6 treatment diminished MDSC generation, restored T cell proportion in both local and systemic immune landscapes and eventually overcame resistance to anti-PD-1 therapy. Our work establishes the evidence for KIRA6 as an impressive agent for abrogating MDSC-mediated immune suppression, killing tumor, and overcoming ICB resistance.

Our findings demonstrate that TRAF6 exacerbates endoplasmic reticulum stress and dysregulates mitophagy, thereby driving pathological HPASMC proliferation and migration during HPH progression. TRAF6 inhibition presents a potential therapeutic intervention against the pathological vascular remodeling in HPH.

G6374 blocks growth of IRE1-dependent cancer cells irrespective of their dependency mode, while sparing IRE1-independent cells. We provide a proof-of-concept for VHL-based degradation of an ER-transmembrane protein, advancing strategies to fully disrupt IRE1.

Our findings highlight the critical role of macrophage PD-1 at the intersection of immune checkpoint blockade, energy expenditure, and metabolic dysfunction. The underscored moonlighting function of macrophage PD-1 may provide a new rationale for combating ICI therapy- and HFD-induced metabolic diseases.