PSMB8 (Proteasome 20S Subunit Beta 8)

Together, these findings suggest that EcPSMB8 may contribute to grouper antiviral defence through coordinated modulation of immune signalling and autophagy. Importantly, a specific polyclonal antibody against EcPSMB8 was generated, providing a useful tool for protein-level analyses and supporting future studies on antiviral immune mechanisms in teleost fish.

Co-culture showed effective spheroid infiltration, cytotoxicity, and structural disruption, with infiltrating CAR T cells displaying higher CD4+ fraction, activation, exhaustion, effector/terminal differentiation, and IFN-γ/TNF-α production. This 3D platform recapitulates critical TME constraints and provides a cost-effective, feasible preclinical tool to assess CAR T therapies beyond conventional 2D assays.

Carfilzomib synergized with BCL2 family protein inhibitors (navitoclax or AZD5991), suggesting that drug combinations could be used to reduce the dose of each drug to minimize toxicity. Notably, thymic carcinomas differed from squamous cell carcinomas in other organs by higher levels of β5i (PSMB8) and constitutive proteasome β5 (PSMB5). We hypothesize that TC (and probably many TH) are uniquely suited for treatment with proteasome inhibitors alone or in combination with selective BH3 mimetics.

In this study, we used ONX 0914, an LMP7/LMP2-selective inhibitor of the IP, to study the effect of IP inhibition on B cells and antibody production...Furthermore, IP inhibition neither impaired vaccine-induced antibody responses, nor affected different B cell populations in two different vaccination models. These findings suggest that IP inhibition does not compromise vaccination efficacy and anti-viral humoral immunity, supporting the potential of IP-targeted therapies for autoimmune diseases.

We tested carfilzomib's efficacy against gastric cancer by subcutaneously implanting nude mice with human gastric epithelial-derived tumors and treating them with carfilzomib, either alone or in combination with 5-fluorouracil (5-FU), a standard-of-care drug. These results strongly suggest that PSMB8 is a suitable candidate for targeted therapy. Moreover, with carfilzomib having robust anti-tumor activity, it has potential as a treatment option for cancers where high levels of PSMB8 are associated with poor overall survival.

Genetic polymorphisms and immune dysregulation contribute to FM-DED pathophysiology, supporting the need for differentiated diagnosis and targeted therapies.

Our findings not only elucidate a novel SFN-mediated tumor-suppressive mechanism via the STAT3/CKMT2-AS1 regulatory axis, but also validate CKMT2-AS1 as a promising therapeutic target for GC intervention.

This study establishes a visceral pain model centered on pancreatic parenchymal nociception rather than secondary neural effects, and for the first time proposes an interconnected regulatory network linking epigenetic modifications, immune reprogramming, and neural plasticity, revealing dual pain pathogenesis mechanisms: (1) immune microenvironment reshaping that potentiates neuroinflammation, and (2) direct ion channel regulation enhancing neuronal excitability. These findings provide a mechanistic foundation for developing methylation-based prognostic biomarkers and multimodal analgesic therapeutic strategies targeting the immuno-neural nexus.

The findings underscore the adaptability of the ubiquitin-proteasome system in maintaining cellular proteostasis by compensatory mechanisms that counteract the lack of Lmp2. The Psmb9KO line can serve as a valuable model for examining the function of immunoproteasomes in proteostasis regulation during early mammalian embryogenesis differentiation.

These results suggest that SFN inhibits gastric cancer growth through the YY1/PSMB8-AS1/miR-888-5p/SLC4A7 axis. Therefore, SFN might be a promising therapeutical agent for GC prevention and therapy.

The effects of this NLRC5 variant on class I MHC regulators suggest a mechanistic connection between the variant and development of ICI-DM. Further work is warranted to determine whether class I MHC molecules can be modulated in patients with the NLRC5Pro191Leu variant requiring ICIs.

A risk model and nomogram based on these genes were developed to assess BRCA prognosis effectively. These tools can improve the prognostic assessment of BRCA patients.