MAPK8 (Mitogen-activated protein kinase 8)

DSS confers cardioprotection against DOX-induced injury by disrupting the vicious circle formed by ROS and JNK, which mediated impairment of mitochondrial quality control, attenuating oxidative stress, and reducing apoptosis. These findings highlight DSS as a promising therapeutic candidate for mitigating chemotherapy-associated cardiotoxicity.

The combination of SNB and FEN represents a promising multi-targeted therapeutic approach against GB. SNB and FEN combination capable of modulating and reprogramming key molecular pathways involved in GB progression and MDR.

Taken together, these results indicate that enhanced tubular epithelial cell death, perturbed cell-cell contacts and barrier function defects are associated with a novel ANLN variant discovered in individuals with non-diabetic proteinuric kidney disease. Enhanced tubular epithelial cell death and perturbed cell-cell junction integrity and barrier function are associated with a novel Anillin coding variant discovered in a cohort of individuals with proteinuric kidney disease.

We also showed that a 16-residue-long arrestin-3-derived peptide binds ZAK and fulfills the scaffolding function of full-length arrestin-3, sensitizing cells to death induced by chemotherapy drugs. These findings demonstrate that arrestin-3 is a versatile facilitator of stress signaling and suggest that functional peptide mimics can be used therapeutically to facilitate drug-induced death of cancer cells.

Furthermore, HY12 effectively inhibited TGF-β1-induced EMT. This work establishes a novel HyT-mediated JNK1 degradation platform and provides a promising therapeutic strategy for EMT-associated disorders.

Collectively, these findings demonstrate that pectolinarigenin derived from T. triandra exerts potent anti-cancer activity in MDA-MB-231 TNBC cells through coordinated modulation of cell cycle progression, apoptotic signaling, and MAPK pathway activity. Further studies are warranted to validate these effects in additional TNBC models.

Competitive inhibition experiments using excess MA or lenalidomide, along with MLN4924 treatment, validated the requirement for ternary complex formation and cullin-RING E3 ligase pathway dependence. P4 effectively downregulates the IL-6/JAK2/STAT3 signaling axis and simultaneously activates dual apoptotic pathways: intrinsic mitochondrial apoptosis (decreased Bcl-2, XIAP, survivin; increased Bax, cytochrome c, cleaved caspases) and ER stress-mediated apoptosis (elevated IRE1, BIP, ATF4, CHOP, p-JNK1, cleaved caspase-12). This work establishes P4 as a promising JAK2-targeting degrader whose anticancer efficacy derives from coordinated target elimination, oncogenic pathway suppression, and dual apoptotic pathway activation, validating natural product PROTACylation as a viable strategy for developing multifunctional anticancer therapeutics.

These effects were mediated through downregulation of the c-Jun N-terminal kinase/p65/c-Jun signaling pathway. In conclusion, these findings demonstrate that xaliproden confers reno-protective effects by mitigating renal tubular epithelial cell damage and improving renal function in DKD, suggesting its potential as a therapeutic option for DKD.

Although most of the current evidence is derived from preclinical studies and substantial challenges remain with respect to dosing accuracy and delivery specificity, the unique multitarget properties of exogenous NO highlight its considerable promise as an adjunctive strategy in dental medicine. This review seeks to provide a comprehensive overview that not only advances fundamental understanding of exogenous NO but also promotes its clinical translation for improved management of dental and oral diseases.

extract (ESH) on lipopolysaccharide (LPS)- and thapsigargin (Tg)-induced inflammatory and ER stress responses, respectively, in ARPE-19 cells...Strong positive correlations were observed between intracellular calcium and VEGF secretion (r = 0.888), and between VEGF mRNA and protein levels (r = 0.843), supporting a potential mechanistic link. Collectively, these findings demonstrate that ESH modulates inflammatory, ER stress, apoptotic, and angiogenic pathways, suggesting its potential as a functional dietary supplement to mitigate RPE dysfunction in AMD and DR.

Mechanistically, AE-EA and OLRF significantly suppressed mitogen-activated protein kinase (MAPK) signaling through inhibition of ERK1/2, JNK1/2, and p38 phosphorylation in both NSCLC cells (p < 0.05). Collectively, these findings demonstrate that AE-EA and OLRF exert pronounced anti-cancer effects in both NSCLC cells through coordinated inhibition of MAPK signaling, induction of cell-cycle arrest, and activation of intrinsic apoptosis, supporting their potential for further development as plant-derived anti-cancer agents.

The Cell Counting Kit‑8 assay was used to investigate the effect of SIVA‑1 silencing on drug sensitivity in AGS/DDP cells by measuring the IC50 of Adriamycin, DDP and vincristine. In conclusion, silencing SIVA‑1 has been shown to modify sensitivity to DDP and biological function in drug‑resistant gastric cancer cells, either directly or indirectly. This phenomenon may be associated with the Bcl‑2/BAX‑mediated, mitochondria‑dependent apoptosis pathway.