Bioscience Reports最新文献

Polysaccharides have gained considerable attention recently because of their anti-tumor and immunoregulatory properties. Its activity depends on the type of fungus that produces it, the extraction method, and the molecular weight.

Materials and methods: This study evaluated the anti-tumor and immunoregulatory properties of Ganoderma parvulum (GP)-derived polysaccharides.

Results: GP crude polysaccharides inhibited mice's lymphoma without cytotoxicity. In vitro studies showed that exopolysaccharides (GEPS) and intrapolysaccharides (GIPS) of G. parvulum inhibited the proliferation of tumor cells, but no cell death was observed. Significantly, GEPS and GIPS increased the production of nitric oxide, TNF-α, MCP-1, and an increase in IL-1β, IL-18, and Caspase-1, while NLRP3 was down-regulated. Also, it decreases the production of IL-10 and IL-6.

Conclusion: These observations suggest that GP-derived polysaccharides may exert anti-tumor activity primarily by activating the host's immune system via macrophage stimulation.

FGR proto-oncogene (Fgr), a member of the Src family kinases, has garnered attention for its potential involvement in apoptotic signaling, yet its role in cardiovascular diseases, particularly acute myocardial infarction (AMI), remains unexplored. This study sought to investigate whether elevated left ventricular Fgr expression alleviates myocardial injury in the infarcted area and whether this protective mechanism is mediated by modulating phosphoinositide 3-kinase (PI3K)/Akt phosphorylation. The transcriptome-wide association study was initially utilized to screen for susceptibility genes in the left ventricle, with findings validated using bulk-RNA sequencing data from a rat model of left anterior descending coronary artery (LAD) ligation; subsequently, human spatial transcriptomics combined with single-nucleus RNA sequencing data confirmed differential expression of Fgr and PI3K/Akt in the infarcted region. Fgr knockdown via siRNA in H9C2 cells and pharmacological inhibition with TL02-59 in rats were conducted to assess cellular survival and cardiac function, respectively. Fgr emerged as a common candidate gene identified through multi-omics data analysis, with its up-regulation confirmed both in vivo and in vitro. Fgr silencing in an in vitro oxygenglucose deprivation model significantly reduced cell survival and suppressed PI3K/Akt phosphorylation, whereas TL02-59 administration in rats subjected to LAD ligation impaired post-infarction cardiac function while concurrently inhibiting PI3K/Akt phosphorylation levels. This study demonstrates that Fgr is markedly up-regulated in AMI and exerts cardioprotective effects, possibly through modulation of PI3K/Akt signaling phosphorylation, thereby underscoring its potential as a therapeutic target.

Proteome, the molecular product of regulatory diktat of the cellular machinery, predicts the behaviour and progression of cancers. Designing effective molecular therapies based on proteins with comprehensive patient stratification remains the mainstay of every translational research. Research on the proteome involves a) identification of biomarkers that, with utmost sensitivity and specificity, reveal significant insights into the disease state and b) understanding the mechanistic underpinnings and rewiring of cellular signaling pathways that drive a particular cancerous pathology. In this review, we give a comprehensive description of the evolution of mass spectrometer-based methods, including labeling strategies available to study the proteome and post-translational modifications in response to various perturbations. We summarize their utility in understanding complex processes of cancers, advance research on cancer therapy by decoding novel biomarkers, identify therapy resistance drivers, and enhance spatial attributes of tumor microenvironment by single-cell proteomics. Finally, some of the challenges in the currently used methods have been discussed.