CUSABIO Quarterly Citation Review: 800 New Product Citations in the First Quarter, Total Citations Hit 26,000!

This study reveals how the gut microbiota influences the progression of multiple myeloma (MM) by regulating serum phosphatidylcholine (PC) levels. It was found that Lachnospiraceae abundance is reduced while PC levels are elevated in MM patients. Lachnospiraceae inhibits PC production from MM cells, thereby enhancing the function of cytotoxic CD8 T cells. Mechanistically, PC promotes SerpinB9 (Sb9) mRNA maturation in MM cells via LIN28A/B, increasing exosomal Sb9 production. Exosomal Sb9 reduces granzyme B (GZMB) expression in CD8 T cells by suppressing tumor protein p53 (TP53) UFMylation, thereby inhibiting the cytotoxic effects of CD8 T cells on MM cells. The study suggests that Lachnospiraceae and PC could serve as potential therapeutic targets for MM.

This study presents a berberine-inspired ionizable lipid nanoparticle (BE) for brain-targeted delivery of nucleic acid therapeutics. The nanoparticles enhance blood-brain barrier penetration via dopamine D3 receptor-mediated endocytosis, improve nucleic acid stability through self-assembly with poly(A) tails, and exhibit minimal immunogenicity with neuroprotective properties. In murine models, BE nanoparticles demonstrate therapeutic potential in Alzheimer’s disease, glioma, and cryptococcal meningitis. This delivery system offers a promising platform for brain-targeted therapeutics.

This study reveals that acteoside (ACT) ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injury (HIRI) by targeting poly(rC)-binding protein 2 (PCBP2). HIRI downregulates PCBP2, destabilizing system Xce and exacerbating ferroptosis. ACT upregulates PCBP2, enhancing its binding to system Xce, maintaining stability, and inhibiting the HIF1a/p300/HMGB1 signaling pathway, thereby reducing M1 macrophage recruitment and inflammation. The key role of PCBP2 in ACT's therapeutic effect on HIRI was confirmed by specifically silencing PCBP2 in hepatocytes. This study provides new targets and strategies for HIRI treatment.

This study reveals that G protein-coupled receptor kinase 2 (GRK2) promotes the hyperproliferation of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) by activating the TRAF2-NF-κB signaling pathway. It was found that GRK2 membrane activity is enhanced in FLSs of RA patients and collagen-induced arthritis (CIA) rats, correlating positively with RA serological markers. Through immunoprecipitation-mass spectrometry, TRAF2 was identified as a novel substrate of GRK2, with the C-terminus of GRK2 binding to the C-terminus of TRAF2 at the Gln340 residue. Experiments showed that increased GRK2 membrane expression and activity facilitate TRAF2 recruitment to the cell membrane, leading to TRAF2 Lys63 polyubiquitination mediated by the E3 ubiquitin ligase TRIM47, which activates NF-κB signaling, causing synovial hyperplasia and abnormal proliferation of FLSs. Both GRK2 inhibitor CP-25 and genetic knockdown improved synovial hyperplasia and FLS proliferation in CIA rats by reducing GRK2 membrane expression and activity. This study provides mechanistic and preclinical rationale for evaluating GRK2 as a therapeutic target for RA.

This article presents a "prof" cocktail CAR-γδ T cell therapy for heterogeneous glioblastoma (GBM). Researchers screened a set of antigens heterogeneously expressed in GBM to build a “target bank” and selected personalized antigen panels based on multiplex immunohistochemistry results of each patient’s tumor sample. Using Vδ1 T cells as CAR vehicles due to their high tissue infiltration and off-the-shelf properties, they developed CAR-Vδ1 T cells with high purity and cytotoxicity. The therapy was tested in patient-derived GBM organoids, showing significantly enhanced efficacy, offering a new strategy for treating heterogeneous solid tumors.

This study identifies apolipoprotein E (ApoE) as a pan-marker for resting zone chondrocytes in mouse and human growth plates through single-cell RNA sequencing and FISH validation. Using ApoE-mCherry knock-in mice, researchers found that these cells express ApoE after the formation of the secondary ossification center, exhibit stem cell properties, and have high proliferative potential and multipotency in vitro. This discovery provides new tools and insights for studying the biology of growth plate chondrocytes.

This study investigates the effects of polyhexamethylene guanidine (PHMG) disinfectant inhalation on pulmonary fibrosis and its underlying mechanisms. It was found that PHMG aerosol induces injury in alveolar type II epithelial cells (AT2) and blocks pulmonary surfactant biogenesis. Mechanistic studies revealed that PHMG disrupts autophagic flux, leading to intracellular accumulation and blocking pulmonary surfactant biogenesis in AT2 cells. Intervention studies using metformin confirmed that autophagy dysfunction mediates the blockage of pulmonary surfactant biogenesis, playing a key role in PHMG-induced pulmonary fibrosis. The findings provide new insights into the mechanisms underlying PHMG-induced fibrosis and offer potential therapeutic targets.

This study investigates the protective effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), against sepsis. It shows that fluoxetine pretreatment significantly reduces sepsis-induced hypertriglyceridemia and cardiac damage, including impaired glucose oxidation, ectopic lipid accumulation, and ventricular stretch, by increasing circulating IL-10 levels independently of peripheral serotonin. IL-10 is essential for this protection. Fluoxetine also promotes peripheral lipid uptake and sustains cardiac glycolysis, thereby protecting the heart from sepsis-induced injury. The study reveals the immunometabolic mechanisms underlying fluoxetine's protective effects and suggests its potential as a prophylactic for sepsis.

This study develops an exosome-based dual-targeting "eat me/don't eat me" strategy for acute liver injury treatment. Researchers engineered exosomes with RLTRKRGLK peptide for LSEC targeting and CD47 for evading macrophage clearance, enabling precise Wnt2 mRNA delivery. In murine models of drug-induced liver injury, this strategy significantly attenuated liver necrosis and enhanced regeneration, demonstrating therapeutic potential and biocompatibility.

This study investigates the reproductive toxicity of medium-chain chlorinated paraffins (MCCPs) in female rats. Both in vivo and in vitro experiments revealed that MCCP exposure induces chromatin condensation and mitochondrial vacuolization in ovarian granulosa cells, significantly alters levels of serum gonadotropins and sex hormones, and affects pathways related to the cell cycle, oocyte meiosis, and DNA damage repair. Transcriptomic and metabolomic analyses showed that MCCPs disrupt steroid hormone biosynthesis and amino acid metabolism. In vitro assays confirmed that MCCPs disturb intracellular calcium homeostasis and generate reactive oxygen species, leading to DNA damage. The findings provide insights into the molecular mechanisms underlying MCCP-induced reproductive toxicity and offer a basis for risk assessment.