Integrative analysis of metabolism subtypes and identification of prognostic metabolism-related genes for glioblastoma.

Increasing evidence has demonstrated that cancer cell metabolism is a critical factor in tumor development and progression; however, its role in glioblastoma (GBM) remains limited. In the present study, we classified GBM into three metabolism subtypes (MC1, MC2, and MC3) through cluster analysis of 153 GBM samples from the RNA-sequencing data of The Cancer Genome Atlas (TCGA) based on 2752 metabolism-related genes (MRGs). We further explored the prognostic value, metabolic signatures, immune infiltration, and immunotherapy sensitivity of the three metabolism subtypes. Moreover, the metabolism scoring model was established to quantify the different metabolic characteristics of the patients. Results showed that MC3, which is associated with a favorable survival outcome, had higher proportions of isocitrate dehydrogenase (IDH) mutations and lower tumor purity and proliferation. The MC1 subtype, which is associated with the worst prognosis, shows a higher number of segments and homologous recombination defects and significantly lower mRNA expression-based stemness index (mRNAsi) and epigenetic-regulation-based mRNAsi. The MC2 subtype has the highest T-cell exclusion score, indicating a high likelihood of immune escape. The results were validated using an independent dataset. Five MRGs (ACSL1, NDUFA2, CYP1B1, SLC11A1, and COX6B1) correlated with survival outcomes were identified based on metabolism-related co-expression module analysis. Laboratory-based validation tests further showed the expression of these MRGs in GBM tissues and how their expression influences cell function. The results provide a reference for developing clinical management approaches and treatments for GBM.

Antibacterial, anti-inflammatory, analgesic, and hemostatic activities of Acanthopanax trifoliatus (L.) merr.

Acanthopanax trifoliatus (L.) Merr (AT) is a medicinal and edible plant with high nutritional value. The biological activity of A. trifoliatus (L.) Merr and its basis for injury treatment are explored in this paper. AT was ethanol-extracted then refined separately with petroleum ether, chloroform, ethyl acetate, and n-butanol. Active ingredients were analyzed, and anti-bacterial, anti-inflammatory, analgesic, and hemostatic effects were explored. Petroleum ether layer (PEL) extract produced the strongest antibacterial effect. Ethyl acetate layer (EAL) extract had the highest active substance content, with strong hemostatic and analgesic activities. Chloroform layer (CL) extract had the strongest anti-inflammatory effect and significantly reduced IL-1ß protein expression. Active ingredients were analyzed using HPLC and UPLC-MS to determine saponin, polyphenol, flavonoid, and characteristic ingredient contents. EAL extract had the highest polyphenol and flavonoid levels, including rutin, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C, which may contribute to its nutritional activities. The study provides a reliable theoretical and practical basis for the applications of AT nutraceutical products.

A Prognostic Microenvironment-Related Immune Signature via ESTIMATE (PROMISE Model) Predicts Overall Survival of Patients With Glioma.

OBJECTIVE: In the development of immunotherapies in gliomas, the tumor microenvironment (TME) needs to be investigated. We aimed to construct a prognostic microenvironment-related immune signature via ESTIMATE (PROMISE model) for glioma. METHODS: Stromal score (SS) and immune score (IS) were calculated via ESTIMATE for each glioma sample in the cancer genome atlas (TCGA), and differentially expressed genes (DEGs) were identified between high-score and low-score groups. Prognostic DEGs were selected via univariate Cox regression analysis. Using the lower-grcade glioma (LGG) data set in TCGA, we performed LASSO regression based on the prognostic DEGs and constructed a PROMISE model for glioma. The model was validated with survival analysis and the receiver operating characteristic (ROC) in TCGA glioma data sets (LGG, glioblastoma multiforme [GBM] and LGG+GBM) and Chinese glioma genome atlas (CGGA). A nomogram was developed to predict individual survival chances. Further, we explored the underlying mechanisms using gene set enrichment analysis (GSEA) and Cibersort analysis of tumor-infiltrating immune cells between risk groups as defined by the PROMISE model. RESULTS: We obtained 220 upregulated DEGs and 42 downregulated DEGs in both high-IS and high-SS groups. The Cox regression highlighted 155 prognostic DEGs, out of which we selected 4 genes (CD86, ANXA1, C5AR1, and CD5) to construct a PROMISE model. The model stratifies glioma patients in TCGA as well as in CGGA with distinct survival outcome (P<0.05, Hazard ratio [HR]>1) and acceptable predictive accuracy (AUCs>0.6). With the nomogram, an individualized survival chance could be predicted intuitively with specific age, tumor grade, Isocitrate dehydrogenase (IDH) status, and the PROMISE risk score. ROC showed significant discrimination with the area under curves (AUCs) of 0.917 and 0.817 in TCGA and CGGA, respectively. GSEA between risk groups in both data sets were significantly enriched in multiple immune-related pathways. The Cibersort analysis highlighted four immune cells, i.e., CD 8 T cells, neutrophils, follicular helper T (Tfh) cells, and Natural killer (NK) cells. CONCLUSIONS: The PROMISE model can further stratify both LGG and GBM patients with distinct survival outcomes.These findings may help further our understanding of TME in gliomas and shed light on immunotherapies.

Synergistic effects and mechanisms of impressic acid or acankoreanogein in combination with docetaxel on prostate cancer.

Prostate cancer (PCa) is a common cancer among males and a leading cause of cancer deaths. Docetaxel (DOC) was recommended in guidelines as the first first-line drug of PCa; however, treatment with high doses of DOC ultimately results in resistance. This study examined the proliferation, viability, and apoptosis of VCaP cells evaluated by the MTT assay, trypan blue exclusion assay, and morphological assessments to investigate the effects and mechanisms of action by impressic acid (E12-1) or acankoreanogein (E13-1), isolated from Acanthopanax trifoliatus (L.) Merr., in combination with DOC in VCaP PCa cells. The research, which also contained cell migration, was examined under a light microscope. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity was assessed by the luciferase reporter assay. Finally, the expression of B-cell lymphoma 2 (Bcl-2), NF-κB, phosphorylated Akt (p-Akt), phosphorylated signal transducer and activator of transcription 3 (p-Stat 3), phosphorylated c-Jun N-terminal kinase (p-JNK), and extracellular signal-related protein kinases 1 and 2 in VCaP cells was evaluated by western blotting. The result is combination of DOC with E12-1 or E13-1 which synergistically inhibited growth, induced apoptosis, and reduced migration of VCaP cells compared with treatment with DOC, E12-1, or E13-1 alone. The potential molecular mechanisms were related to significant decreases in the expression of NF-κB, Bcl-2, p-Stat 3, p-JNK, and p-Akt in VCaP cells. DOC combined with E12-1 or E13-1 may be an effective approach for inhibiting the growth and apoptosis of PCa cells, thus making it possible to reduce the dose of DOC in patients with PCa who experience systemic toxicity.

Biosynthesis, Antibacterial Activity and Anticancer Effects Against Prostate Cancer (PC-3) Cells of Silver Nanoparticles Using Dimocarpus Longan Lour. Peel Extract.

Metal nanoparticles, particularly silver nanoparticles (AgNPs), are developing more important roles as diagnostic and therapeutic agents for cancers with the improvement of eco-friendly synthesis methods. This study demonstrates the biosynthesis, antibacterial activity, and anticancer effects of silver nanoparticles using Dimocarpus Longan Lour. peel aqueous extract. The AgNPs were characterized by UV-vis absorption spectroscopy, X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscope (FTIR). The bactericidal properties of the synthesized AgNPs were observed via the agar dilution method and the growth inhibition test. The cytotoxicity effect was explored on human prostate cancer PC-3 cells in vitro by trypan blue assay. The expressions of phosphorylated stat 3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. The longan peel extract acted as a strong reducing and stabilizing agent during the synthesis. Water-soluble AgNPs of size 9-32 nm was gathered with a face-centered cubic structure. The AgNPs had potent bactericidal activities against gram-positive and gram-negative bacteria with a dose-related effect. AgNPs also showed dose-dependent cytotoxicity against PC-3 cells through a decrease of stat 3, bcl-2, and survivin, as well as an increase in caspase-3. These findings confirm the bactericidal properties and explored a potential anticancer application of AgNPs for prostate cancer therapy. Further research should be focused on the comprehensive study of molecular mechanism and in vivo effects on the prostate cancer.

Effects of green-synthesized silver nanoparticles on lung cancer cells in vitro and grown as xenograft tumors in vivo.

Silver nanoparticles (AgNPs) have now been recognized as promising therapeutic molecules and are extending their use in cancer diagnosis and therapy. This study demonstrates for the first time the antitumor activity of green-synthesized AgNPs against lung cancer in vitro and in vivo. Cytotoxicity effect was explored on human lung cancer H1299 cells in vitro by MTT and trypan blue assays. Apoptosis was measured by morphological assessment, and nuclear factor-κB (NF-κB) transcriptional activity was determined by a luciferase reporter gene assay. The expressions of phosphorylated stat3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. AgNPs showed dose-dependent cytotoxicity and stimulation of apoptosis in H1299 cells. The effects on H1299 cells correlated well with the inhibition of NF-κB activity, a decrease in bcl-2, and an increase in caspase-3 and survivin expression. AgNPs significantly suppressed the H1299 tumor growth in a xenograft severe combined immunodeficient (SCID) mouse model. The results demonstrate the anticancer activities of AgNPs, suggesting that they may act as potential beneficial molecules in lung cancer chemoprevention and chemotherapy, especially for early-stage intervention.