Background: Pancreatic cancer is a deadly cancer with a poor prognosis. In light of mounting evidence that basement membrane genes (BMGs) play a role in the development of cancer, we sought to examine the prognostic importance and role of BMGs in pancreatic ductal adenocarcinoma (PDAC) patients. Methods: BMGs were obtained from previous top research studies. The clinical and messenger ribonucleic acid expression data were retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets, respectively. Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used for the PDAC risk modeling and gene identification. The Kaplan-Meier method was used to compare outcomes between the low- and high-risk groups. Finally, we analyzed small-molecule drugs that could be used to target BMGs for treatment using the Enrichr data set and validated the function of the tubulointerstitial nephritis antigen (TINAG) in pancreatic cancer. Results: We successfully constructed and validated a 7 BMG-based model to predict PDAC patient outcomes. Additionally, we discovered that 7 BMG-based model was an independent predictive factor for PDAC. According to our functional analysis, the majority of the signaling pathways enriched in BMGs were those connected to malignancy. Immune cell infiltration and immunological checkpoints were also linked to the BMG-based model. Further, we identified 5 small-molecule drugs that may be useful in treating PDAC patients. We also found that TINAG promoted cell proliferation in pancreatic cancer. Conclusions: Our study extended understandings of how BMGs work in PDAC. We identified a credible predictive biomarker for PDAC patients’ survival.

Acute kidney injury (AKI) is a global public health hazard with high morbidity and mortality. Sepsis accounts for nearly half of all causes of AKI. Scientists have made a great effort to explore effective therapeutic agents with limited side effects in the treatment of AKI, but have had little success. With the development of gut flora study, Akkermansia muciniphila (A. muciniphila) has been proven to prevent different organs by regulating the inflammatory response. However, the reno-protective function is still unknown. Here, the AKI model was induced using lipopolysaccharide (LPS) in mice with or without pretreatment of A. muciniphila. Renal function and histological change were measured. Inflammatory factors were detected by ELISA and rt-PCR. TLR4/NF-κB signaling factors and NLRP3 inflammasome were tested by western blot and immunohistochemistry. Pretreatment of A. muciniphila markedly inhibited inflammatory response and ameliorated kidney histopathological changes. Furthermore, the TLR4, p-NF-κB p65, and downstream IκBα were notably activated in the model group and inhibited by A. muciniphila. A similar effect was found in the regulation of NLRP3 inflammasome. In conclusion, pretreatment with A. muciniphila could protect against LPS-induced AKI by inhibition of the TLR4/NF-κB pathway and NLRP3 inflammasome activation. It may be a new therapeutic strategy for AKI prevention and treatment in the future.

With the abuse of antibiotics, bacterial antibiotic resistance is becoming a major public healthcare issue. Natural plants, especially traditional Chinese herbal medicines, which have antibacterial activity, are important sources for discovering potential bacteriostatic agents. This study aimed to develop a fast and reliable method for screening out antimicrobial compounds targeting the MRSA membrane from Psoralea corylifolia Linn. seed. A UPLC-MS/MS method was applied to identify the prenylated flavonoids in major fractions from the extracts of Psoralea corylifolia Linn. seed. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of different fractions and compounds. The morphological and ultrastructural changes of MRSA were determined by scanning electron microscopy (SEM). The membrane-targeting mechanism of the active ingredients was explored by membrane integrity assays, membrane fluidity assays, membrane potential assays, ATP, and ROS determination. We identified eight prenylated flavonoids in Psoralea corylifolia Linn. seed. The antibacterial activity and mechanism studies showed that this type of compound has a unique destructive effect on MRSA cell membranes and does not result in drug resistance. The results revealed that prenylated flavonoids in Psoralea corylifolia Linn. seeds are promising candidates for the development of novel antibiotic agents to combat MRSA-associated infections.

Peritoneal fibrosis (PF), a major complication of long-term peritoneal dialysis (PD), is characterized by excessive extracellular matrix (ECM) deposition mediated by activated myofibroblasts (MyoFs). While mesenchymal transition of mesothelial cells has been widely studied, the cellular origins of MyoFs remain incompletely defined. Recent evidence suggests pericytes-mural cells surrounding microvessels-may contribute to fibrosis in other organs, but their role in PF pathogenesis is undefined. This study aimed to clarify pericyte-myofibroblast transition (PMT) as a key mechanism of PF, investigate the role of platelet-derived growth factor receptor-β (PDGFRβ) signaling in orchestrating PMT, and evaluate the therapeutic potential of natural triterpenoid asiaticoside (ASI) against PDGFRβ-driven fibrosis. Through single-cell RNA sequencing of chlorhexidine gluconate (CG)-induced PF mice, we identified two MyoFs subpopulations (Fibro5 and Fibro7) exhibiting pericyte lineage signatures, with trajectory inference confirming their differentiation from pericytes during fibrosis. Pharmacological and genetic approaches demonstrated that PDGFRβ signaling orchestrates PMT, as evidenced by upregulated α-smooth muscle actin (α-SMA), PDGFRβ, and ECM markers (Collagen I, fibronectin) in PF mice and TGF-β1/PDGF-BB-stimulated mouse peritoneal microvascular pericytes. Remarkably, ASI attenuated PF by suppressing PDGFRβ expression by 50 % and disrupting pericyte-endothelial interactions, which led to a marked reduction in peritoneal thickness (by ∼ 69 %) and collagen deposition (by ∼ 78 %). Proteomics analysis provided a perspective for analyzing the downstream mechanisms. Mechanistically, ASI mimicked PDGFRβ knockout effects, reducing MyoFs accumulation and abrogating PDGFRβ-induced Erk and Pi3k/Akt activation. Our findings repositioned pericytes as pivotal contributors to PF and proposed ASI as a therapeutic agent against PDGFRβ-driven PMT, which provided a new perspective for antifibrotic strategies.

Myasthenia gravis (MG) is an autoimmune di sease characterized by muscle weakness. Experimental autoimmune myasthenia gravis (EAMG) serves as an animal model for MG research. Despite advancements in EAMG modeling, limited drug absorption and variability in disease manifestation among animals resulted in a low success rate of model induction. This study aimed to optimize and standardize the modeling process by exploring different induction conditions to improve success rates. We employed female Lewis rats and C57BL/6 mice to compare their sensitivity to model induction and applied a controlled variable approach to acetylcholine receptor (AChR) and H37Ra dosage, mixing time, and injection sites. Results showed that Lewis rats were more suitable than C57BL/6 mice, and 75 µg AChR peptides were more effective than 50 µg. The immune-boosting effect of 1 mg H37Ra Mycobacterium tuberculosis was weaker than 2 mg. While drug mixing time had little impact, increasing injection sites on backs and including foot pads injection, significantly improved drug absorption.