ATF6 (Activating Transcription Factor 6)

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.

In addition, we highlight stress granules (SGs) and the prevalence of protein-protein interactions mediated by intrinsically low-complexity domains (LCDs) in the UPR as potential new avenues for immune modulation. Finally, we discuss future directions for leveraging UPR modulation in immunotherapy, infectious disease, and chronic inflammatory disorders.

Thus, prolonged ATF6α activation drives ER stress, leading to glycolysis-dependent immunosuppression in liver cancer and sensitizing to ICB. Our findings suggest that persistently activated ATF6α is a tumour driver, a potential stratification marker for ICB response and a therapeutic target for HCC.

In conclusion, our findings indicate that CDA induces sustained ER stress, thereby activating the PERK/ATF4/CHOP pathway to trigger apoptosis in HeLa cells. Together, these findings define CDA as a novel marine-derived depsidone scaffold that induces apoptosis via sustained ER stress signaling and provides a basis for future structure optimization.

Transcriptomic analysis and quantitative reverse transcription PCR (qRT-PCR) revealed that necrotic cell-induced XBP1u was associated with altered expression of XBP1-related genes, while XBP1 knockdown produced similar transcriptional changes and enhanced the effects of necrotic cell treatment. These findings suggest that necrotic cells impair canonical IRE1α-XBP1 signaling and induce transcriptional reprogramming in glioblastoma cells, which may contribute to tumor progression.

Moreover, Buyang Huanwu Decoction and Didang Decoction decreased the expression of CD68~+α-SMA~+ and CD68~+α-SMA~+COL-Ⅰ~+ in renal tissue and down-regulated the expression level of α-SMA mRNA and the mRNA and protein levels of ATF6, TXNDC5, and TGF-β1 in renal tissue. In conclusion, Buyang Huanwu Decoction and Didang Decoction can regulate ATF6/TXNDC5 signaling pathway, down-regulate TGF-β1 expression, reduce the occurrence of MMT in chronic kidney disease, reduce renal fibrosis, and improve renal injury, so as to play a protective role in kidney.

Formononetin could alleviate pathological changes after chronic SCI in rats, improve behavioral scores, and promote the recovery of spinal cord nerve function. The specific mechanism may be related to the inhibition of necrotic apoptosis mediated by endoplasmic reticulum stress signaling pathway.

Future directions include optimizing combination regimens, identifying predictive biomarkers, and advancing personalized approaches. Translating these insights into clinical trials is critical to validate ER stress modulation as a viable strategy for improving NSCLC outcomes, offering a promising avenue to address unmet needs in this aggressive malignancy.

Importantly, CD11b knockdown not only markedly decreased SINV replication but also significantly reduced the ATF6, CHOP, and IL-11 expression, coupled with impairment of the FAK, TSC2, AKT, and ERK signaling pathways. These early cellular events induced by SINV via CD11b are implicated in SINV replication and pathogenicity, suggesting CD11b may be a potential target for combating SINV infection, pending in vivo validation.

Ca2+ signaling is not required for phenazine mitochondrial toxicity. The greater sensitivity of cancer cells to phenazine cytotoxicity necessitates use of primary cells when studying host responses to bacterial phenazines. Enhanced ROS production and ciliotoxicity in CF-CRS may contribute to susceptibility to P. aeruginosa infection.

We discuss the potential of integrating UPR targeting with other therapies, such as immune checkpoint inhibition, highlighting emerging strategies to improve therapeutic efficacy and overcome resistance. These recent insights underscore the importance of UPR as a novel therapeutic target for cancer treatment.

In T24 BLCA cells, ASP inhibits ATF6, which prevents apoptosis resistance and migration and alters the expression of inflammatory genes and EMT markers. According to these findings, ASP is a promising natural substance that targets the endoplasmic reticulum (ER) stress-ATF6 axis in BLCA. It has a unique multi-target capability that allows it to simultaneously control inflammation, tumour proliferation and metastasis, providing a therapeutic advantage over conventional single-target agents.