CAPN1 (Calpain 1)

Additionally, ROC curve analysis demonstrated the potential of LENG8-AS1 as a valuable biomarker for CRC. Overall, these findings suggest that LENG8-AS1 may serve as a biomarker for CRC, with its increased expression being associated with tumor progression and poor patient prognosis.

Rather, its overexpression in spinal CaMKII neurons directly promotes nociceptive signaling, most likely through disruption of plasma membrane calcium dynamics. Collectively, the results identify CAPN1 as a candidate therapeutic target for the clinical treatment and prevention of PINP.

Paeoniflorin induces melanoma cell senescence through the ER stress/calpain1/ERK5/p27 signaling axis, suggesting its potential as a novel therapeutic strategy against SKCM.

Our findings suggest that elevated levels of C2orf49-DT, CAPN10-DT, and LOC105371795 may be associated with increased mortality rates in CRC patients. These non-coding RNAs are associated with pathways that promote cell proliferation and are proposed as potential biomarkers for diagnosing and predicting CRC.

Therefore, this article discusses the expression and function of calpain-1 and calpain-2 (ubiquitous calpains) in various innate (epithelial, endothelial, dendritic, mast, and NK cells, as well as macrophages) and adaptive (T and B cells) immune cells, affecting inflammation and immune regulation. As inflammatory diseases are on the rise due to several factors, such as environment, lifestyle, and an aging population, we must not just investigate but strive for a deeper understanding of the inflammation and immunoregulation under the calpain system (calpain-1 and calpain-2 and their endogenous negative regulator calpastatin) lens, which is ubiquitous and senses cytosolic Ca2+ changes to impact immune response.

These persistent molecular differences suggest spontaneous weaning as the optimal model for healthy mammary gland regression, whereas forced weaning sustains alterations in calpain-2 and regulatory miRs that may increase post-partum breast cancer risk. The potential long-term influence of lactation duration on breast cancer development warrants further consideration in both clinical and public health contexts.

These findings indicate that CAPN-1 and CAPN-2 may exert antagonistic roles in breast cancer, but importantly, this effect was restricted to HCC1937 cells, representing a basal A TNBC subtype. Validation in additional basal A models and patient-derived samples will be essential to confirm these results. Our study, therefore, provides preliminary, model-specific insights into calpain regulation in TNBC and suggests that future therapeutic strategies should carefully account for subtype heterogeneity.

However, this peptide inhibitor was not effective in vivo at reducing metastasis under the conditions used (vehicle vs. CAST, 1.12 ± 1.35 lung metastases per mm2 vs. 0.34 ± 0.20 metastases per mm2), likely due to rapid clearance, as indicated by the short serum half-life. This work demonstrates that calpain-1/2 disruption effectively abrogates metastasis and provides rationale for development of effective calpain inhibitors.

Future research should aim to validate these findings using larger, balanced cohorts and include longitudinal CSF and serum analysis. Experimental in vitro or in vivo studies investigating CAPN1 inhibition and its impact on HMGB1-related signalling are necessary to explore therapeutic implications.

RT-qPCR analysis further confirmed significant upregulation of mRNA expression levels of randomly selected BAG3, EIF2AK2, KIF5B, and RAB24 in HCC cell lines, consistent with the bioinformatics analysis findings. This study showed that the 41 obtained ARGs, such as ATG16L1, ATG4B, BAG3, KIF5B, MAPK1, RAB24, and SOGA1, these findings suggest that ARGs may serve as prognostic biomarkers for HCC, warranting further validation in clinical cohorts and functional studies.

Although the precise CAPN2 targets during adipocyte differentiation remain unknown, CAPN1 was identified as the main isoform responsible for chromatin remodelling by histone H3 cleavage at MCE-to-ED transition. These findings underscore the critical role of phase-specific calpains in the adipogenic program, revealing them as potential therapeutic targets for obesity and metabolic disorders.

Kaempferol acts as a multi-target therapeutic agent in CCA by inducing ER stress, autophagy, and triggering necroptosis when combined with zVAD-FMK and LCL-161, while enhancing immunogenic cell death. These findings support its potential as a novel immunogenic cell death-based treatment strategy for CCA.