GFAP Recombinant Rabbit Monoclonal Antibody

Patients with advanced-stage cancers often suffer from severe pain caused by bone metastasis and destruction, for which effective treatment options are limited. Liu-Shen-Wan (LSW) is a widely recognized herbal formula utilized for pain relief. This study aims to elucidate the effects of LSW on bone cancer pain (BCP). In this study, the pharmacology of LSW on BCP was screened by network pharmacology. A BCP model was conducted using Walker 256 cells. Paw withdrawal threshold and paw withdrawal latency were employed as measures to assess the pain threshold in rats. The pathways and cell types of LSW against BCP were explored. Next, the impact of LSW on Walker 256 cells was evaluated, and UPLC-MS was utilized to identify the active ingredients of LSW. Furthermore, the effects of the key active ingredient, Bufalin, on the BCP rats were evaluated. There were 275 shared targets between LSW and BCP, which were enriched in neural tissue ligand-receptor interaction pathway. LSW increased pain threshold and decreased inflammatory cytokines levels in BCP rats by inhibiting PI3K/Akt and transient receptor potential vanilloid 1 (TRPV1) signaling through astrocytes and microglia. LY294002 further alleviated BCP in rats, while the effects were reversed after treatment with insulin-like growth factor 1 (IGF-1). Both LSW and its active ingredient Bufalin were shown to inhibit the viability and migration of Walker 256 cells and induce apoptosis. Bufalin appears to be the key active ingredient of LSW and exerts its pain-relieving effects by suppressing PI3K/Akt and TRPV1 signaling in BCP.

Post-operative progression and chemotherapy resistance are the main causes of treatment failure in glioma patients. There is a lack of ideal prediction models for post-operative glioma patient progression and drug sensitivity. We aimed to develop a prognostic model of parthanatos mRNA biomarkers for glioma outcomes. A total of 11 parthanatos genes were obtained from ParthanatosCluster database. ConsensusClusterPlus and R “Limma” package were used to cluster The Cancer Genome Atlas (TCGA)-glioma cohort and analyze the differential mRNAs. Univariate Cox regression analysis, random survival forest model, and least absolute shrinkage and selection operator (LASSO) regression analysis were used to determine the nine ParthanatosScore prognostic genes combination. ParthanatosScore was verified by 656 patients and 979 patients in TCGA and CGCA-LGG/GBM datasets. Differences in genomic mutations, tumor microenvironments, and functional pathways were assessed. Drug response prediction was performed using pRRophetic. Kaplan–Meier survival analysis was analyzed. Finally, COL8A1 was selected to evaluate its potential biological function and drug sensitivity of temozolomide and AZD3759 in glioma cells. ParthanatosScore obtained a combination of nine glioma prognostic genes, including CD58, H19, TNFAIP6, FTLP3, TNFRSF11B, SFRP2, LOXL1, COL8A1, and FABP5P7. In the TCGA-LGG/GBM dataset, glioma prognosis was poor in high ParthanatosScore. Low-score glioma patients were sensitive to AZD3759_1915, AZD5582_1617, AZD8186_1918, Dasatinib_1079, and Temozolomide_1375, while high-score patients were less sensitive to these drugs. Compared with HA cells, COL8A1 was significantly over-expressed in LN229 and U251 cells. Silencing COL8A1 inhibited the malignant characterization of LN229 and U251 cells. Temozolomide and AZD3759 also promoted parthanatos gene expression in glioma cells. Temozolomide and AZD3759 inhibited COL8A1 expression and cell viability and promoted apoptosis in glioma cells and PGM cells. ParthanatosScore can accurately predict clinical prognosis and drug sensitivity after glioma surgery. Silencing COL8A1 inhibited the malignant characterization. Temozolomide and AZD3759 inhibited COL8A1 expression and cell viability and promoted apoptosis and parthanatos gene expression, which is a target to improve glioma.

Glioblastoma stem cells (GSCs) have been implicated in the self-renewal and treatment resistance of glioblastoma (GBM). Our previous study found that 4,5-dimethoxycanthin-6-one has the potential to inhibit GBM cell proliferation. This current study aims to elucidate the molecular mechanism underlying the effects of 4,5-dimethoxycanthin-6-one in GBM development. The effect of 4,5-dimethoxycanthin-6-one on GSC formation and differentiation was explored in human GBM cell lines U251 and U87. Subsequently, 4,5-dimethoxycanthin-6-one binding to tetraspanin 1 (TSPAN1) / transmembrane 4 L six family member 1 (TM4SF1) was analyzed by molecular simulation docking. Co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were used to assess the interactions between TSPAN1 and TM4SF1 in GSCs. Cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assay. To evaluate cell migration, invasion and apoptosis, we employed wound healing assay, transwell and flow cytometry, respectively. Furthermore, subcutaneous xenograft tumor models in nude mice were constructed to evaluate the impact of 4,5-dimethoxycanthin-6-one on GSCs in vivo by examining tumor growth and histological characteristics. 4,5-Dimethoxycanthin-6-one inhibited GSC formation and promoted stem cell differentiation in a concentration-dependent manner. Molecular docking models of 4,5-dimethoxycanthin-6-one with TM4SF1 and TSPAN1 were constructed. Then, the interaction between TSPAN1 and TM4SF1 in GSC was clarified. Moreover, 4,5-dimethoxycanthin-6-one significantly inhibited the expressions of TM4SF1 and TSPAN1 in vitro and in vivo. Overexpression of TSPAN1 partially reversed the inhibitory effects of 4,5-dimethoxycanthin-6-one on GSC formation, proliferation, migration and invasion. 4,5-Dimethoxycanthin-6-one inhibited GBM progression by inhibiting TSPAN1/TM4SF1 axis. 4,5-Dimethoxycanthin-6-one might be a novel and effective drug for the treatment of GBM.

Background: Postoperative cognitive dysfunction (POCD) is a common and serious complication in older adult patients. While the tyrosine kinase ABL1 has been implicated in neurodegenerative diseases, its specific role in POCD remains unexplored. This study aims to investigate whether ABL1 influences POCD in aged mice by regulating microglial autophagy and neuroinflammation via the mTOR/ULK1 pathway. Methods: An aged mouse model of POCD was established, and ABL1 silencing and 3-Methyladenine (3-MA) were used to intervene in mice. The Novel Object Recognition Test (NORT) assessment and water maze experiment were conducted. qRT-PCR quantified the mRNA levels of inflammatory cytokines, hippocampal damage was assessed by immunofluorescence, and western blot analyzed the protein expression of autophagy-related genes and the mTOR/ULK1 pathway. Co-Immunoprecipitation (CO-IP) was used to detect the binding of ABL1 to mTOR. In vitro experiments used microglial cells, where ABL1 silencing and rapamycin (Rapa) were used to construct a cellular model and conduct relevant cell experiments. Results: ABL1 silencing or 3-MA rescued cognitive deficits in aged POCD mice, concurrently mitigating neuroinflammation, microglial activation, and aberrant autophagy in the hippocampus. We established ABL1 as a direct binding partner of mTOR. Silencing ABL1 activated the mTOR pathway, leading to ULK1 inhibition and suppression of autophagic activity. Consistent with these in vivo results, ABL1 knockdown in microglia attenuated pro-inflammatory responses, inhibited autophagy, and conferred protection against neuronal damage. Conclusions: ABL1 exacerbates POCD in aged mice by promoting microglial autophagy and neuroinflammation through the mTOR/ULK1 signaling pathway. Targeted inhibition of ABL1 may represent a novel therapeutic strategy for preventing or treating POCD.