CUSABIO Monthly Citation Review: 260 New Product Citations in April, Total Citations Hit 26,500!

This article investigates the role of nociceptor neurons in the progression of pancreatic ductal adenocarcinoma (PDAC) and cancer pain. The study reveals that nociceptor neurons interact with cancer-associated fibroblasts (CAFs) and suppress natural killer (NK) cells, thereby promoting PDAC progression and cancer pain. In PDAC patients, tumor innervation by nociceptor neurons is negatively correlated with NK cell infiltration but positively correlated with pain intensity. The research also suggests that targeting nociceptor neurons or CGRP signaling may be a promising therapeutic strategy for PDAC and cancer pain. The study highlights the immune regulatory role of nociceptor neurons in the PDAC microenvironment and provides new targets for cancer therapy.

This article investigates the role of CMPK2 in hepatocytes in the development of metabolic dysfunction-associated steatohepatitis (MASH). CMPK2 is significantly upregulated in the livers of obese individuals and MASH mice, correlating with inflammation and fibrosis. CMPK2 expression increases predominantly in hepatocytes during the MASH stage. Genetic knockout or pharmacological inhibition of CMPK2 alleviates liver injury, inflammation, and fibrosis in mice. The study also reveals that CMPK2 promotes NLRP3 inflammasome activation and pyroptosis by increasing oxidized mitochondrial DNA (ox-mtDNA). The CMPK2 inhibitor NDGA mitigates diet-induced metabolic disorders, inflammation, and fibrosis, identifying CMPK2 as a promising therapeutic target for MASH.

This article reveals the molecular changes across tissues during mammalian aging through integrated proteomic, metabolomic, and metagenomic analyses. The study finds that aging induces widespread reprogramming of chronic inflammation, characterized by activation of the complement system in plasma and accumulation of immunoglobulins in multiple solid tissues. Aging also significantly disrupts inter-tissue metabolic coupling, activities of polyunsaturated fatty acid metabolism, and gut microbiota homeostasis. Aged mice exhibit a marked decrease in Escherichia and an increase in Helicobacter, strongly correlating with alterations in omega-3 and omega-6 fatty acid abundances. Through multi-omics integration, key molecular hubs driving organismal responses to aging are identified. These findings provide deeper insights into the development of healthy aging from a cross-tissue perspective.

This article investigates the impact of butyrate on food allergy and its underlying mechanisms. The study finds that children with food allergy have significantly lower levels of short-chain fatty acids (SCFAs) in their feces compared to healthy controls. In an ovalbumin (OVA)-sensitized mouse model, butyrate significantly alleviates allergic reactions, outperforming other SCFAs. Butyrate enhances intestinal barrier function by inhibiting oxidative stress-mediated Notch signaling, reducing food antigen absorption and immune responses. It also modulates gut microbiota structure and increases anti-inflammatory and antioxidant metabolites. These findings provide a theoretical basis for using butyrate as a preventive and therapeutic strategy for food allergy.

This study reveals that chemotherapy-induced senescence in glioblastoma cells promotes the recruitment and M2-like polarization of tumor-associated macrophages (TAMs) via DDX58-mediated STAT1 signaling, creating a pro-cancer immune microenvironment. Using in vitro cell models, in vivo mouse models, and CRISPR-Cas9 screening, the research identifies the critical role of the DDX58-STAT1-CSF1 axis in glioblastoma cell senescence. It also shows that combining a STAT1 inhibitor with temozolomide effectively suppresses tumor growth and extends mouse survival, offering new insights for improving traditional treatment strategies.

This study addresses intervertebral disc degeneration (IDD) by identifying the loss of MFG-E8 protein and the degradation of glycosaminoglycans (GAGs) in the nucleus pulposus as key factors for IDD progression. The researchers synthesized a glucomannan octanoate (GMOC) that is highly resistant to enzymatic degradation and forms complexes with MFG-E8 to maintain a healthy nucleus pulposus cell phenotype. In rat and rabbit models, GMOC injection enriched MFG-E8 in situ, promoted nucleus pulposus tissue regeneration, and significantly alleviated IDD symptoms, offering a novel therapeutic strategy for IDD.

This study reveals that p38-mediated ACSL4 phosphorylation drives the growth of esophageal squamous cell carcinoma (ESCC) by promoting Src myristoylation and activating the ERK1/2 signaling pathway. The research shows a positive correlation between p38 and ERK1/2 activation. p38 phosphorylates ACSL4 at T679, enhancing its enzymatic activity and increasing the production of myristoyl-CoA (C14:0 CoA), which subsequently promotes Src myristoylation. In vitro and in vivo models demonstrate that ACSL4 knockdown inhibits ESCC cell proliferation and tumor growth, while ACSL4 overexpression has the opposite effect. Moreover, ACSL4 is upregulated in ESCC tissues and is associated with poor prognosis. This study provides potential new targets for the prevention and treatment of ESCC.

This study reveals that gut microbiota dysbiosis plays a significant role in the pathogenesis of systemic lupus erythematosus (SLE). Fecal microbiota transplantation (FMT) from healthy mice to lupus mice significantly ameliorated lupus-like symptoms, reduced autoantibody levels, and decreased renal B cell infiltration. Microbiota profiling showed an enrichment of Lactobacillus johnsonii post-FMT, which correlated with purine metabolites. The inosine produced by L. johnsonii effectively alleviated lupus pathogenesis by inhibiting B cell differentiation and migration. Mechanistically, inosine reprograms B cells through the ERK-HIF-1α signaling pathway. This study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome-based therapeutic approaches.

This study develops an "off-the-shelf" artificial proregenerative macrophage (artM) for treating pressure ulcers. The artM is composed of PLGA microspheres loaded with proteins derived from M2 macrophages and coated with a macrophage cell membrane. It maintains bioactivity after long-term cryostorage and mimics the anti-inflammatory and proregenerative functions of endogenous macrophages, such as promoting M2 macrophage polarization, releasing anti-inflammatory cytokines and growth factors, neutralizing endotoxins and proinflammatory cytokines, and enhancing TH2 immune response. In a mouse model of deep tissue pressure injury, artM induces tissue regeneration by modulating the inflammatory microenvironment, promoting angiogenesis, reducing scar deposition, and accelerating skin appendage renewal. Even in macrophage-depleted mice, artM effectively exerts immunomodulatory and proangiogenic functions comparable to autologous macrophages. This research offers a cell-free, off-the-shelf, and proreparative alternative to immune cell therapy for chronic wound management and holds potential for repairing other tissue injuries.

This study used single-cell transcriptomics to identify a unique subpopulation of malignant hepatoblast-like cells in hepatoblastoma that are closely associated with poor prognosis in patients. These cells maintain their stem-like features by producing insulin-like growth factor 2 (IGF2), which promotes abnormal cholesterol accumulation via SREBF2. Additionally, IGF2 stimulates fibroblast 2 to secrete collagen 1, enhancing tumor malignancy through the collagen 1/integrin α1 signaling pathway. The study also found that serum IGF2 levels in hepatoblastoma patients may serve as a diagnostic biomarker for advanced hepatoblastoma. These findings provide new targets and insights for the diagnosis and treatment of hepatoblastoma.