Despite several clinicopathological factors being integrated as prognostic biomarkers, the individual variants and risk stratification have not been fully elucidated in lower grade glioma (LGG). With ...the prevalence of gene expression profiling in LGG, and based on the critical role of the immune microenvironment, the aim of our study was to develop an immune-related signature for risk stratification and prognosis prediction in LGG.
RNA-sequencing data from The Cancer Genome Atlas (TCGA), Genome Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) were used. Immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort). Univariate, multivariate cox regression, and Lasso regression were employed to identify differentially expressed immune-related genes (DEGs) and establish the signature. A nomogram was constructed, and its performance was evaluated by Harrell's concordance index (C-index), receiver operating characteristic (ROC), and calibration curves. Relationships between the risk score and tumor-infiltrating immune cell abundances were evaluated using CIBERSORTx and TIMER.
Noted, 277 immune-related DEGs were identified. Consecutively, 6 immune genes (
,
,
,
,
, and
) were identified as risk signature and Kaplan-Meier curve, ROC curve, and risk plot verified its performance in TCGA and CGGA datasets. Univariate and multivariate Cox regression indicated that the risk group was an independent predictor in primary LGG. The prognostic signature showed fair accuracy for 3- and 5-year overall survival in both internal (TCGA) and external (CGGA) validation cohorts. However, predictive performance was poor in the recurrent LGG cohort. The CIBERSORTx algorithm revealed that naïve CD4
T cells were significant higher in low-risk group. Conversely, the infiltration levels of M1-type macrophages, M2-type macrophages, and CD8
T cells were significant higher in high-risk group in both TCGA and CGGA cohorts.
The present study constructed a robust six immune-related gene signature and established a prognostic nomogram effective in risk stratification and prediction of overall survival in primary LGG.
The hippocampus, a brain region critical for learning, memory and emotional processing, maintains its capacity to undergo structural plasticity throughout life. Hippocampal structural plasticity can ...be modulated by a number of intrinsic and extrinsic factors. This study investigated the effects of adiponectin, an adipocyte-derived hormone, on dendritic growth, arborization, and spinogenesis in mature granule neurons of the hippocampal dentate gyrus generated during embryonic (early-born) or early postnatal (late-born) stages. We found that adiponectin deficiency reduced dendritic length, branching and spine density of granule neurons. The reduction was more evident in early-born granule neurons than in late-born granule neurons. Intracerebroventricular infusion of adiponectin for 1 week increased of dendritic spines and arbor complexity in late-born granule neurons. Moreover, adiponectin deficiency decreased the production of adult-born new granule neurons through suppressing neural progenitor cell proliferation and differentiation, whereas intracerebroventricular adiponectin infusion increased the proliferation of neural progenitor cells in adult dentate gyrus. These results suggest that adiponectin plays an important role in dendritic spine remodeling and neurogenesis in the dentate gyrus.
Ellagic acid (EA) is a kind of polyphenol compound extracted from a variety of herbs, such as paeoniae paeoniae, raspberry, Chebule, walnut kernel, myrrh, loquat leaf, pomegranate bark, quisquite, ...and fairy herb. It has anti-tumor, anti-oxidation, anti-inflammatory, anti-mutation, anti-bacterial, anti-allergic and multiple pharmacological properties. Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors, mainly through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, inhibiting tumor cell metastasis and invasion, inducing autophagy, affecting tumor metabolic reprogramming and other forms of anti-tumor efficacy. Its molecular mechanism is mainly reflected in inhibiting the proliferation of tumor cells through VEGFR-2 signaling pathway, Notch signaling pathway, PKC signaling pathway and COX-2 signaling pathway. PI3K/Akt signaling pathway, JNK (cJun) signaling pathway, mitochondrial pathway, Bcl-2 / Bax signaling pathway, TGF-β/Smad3 signaling pathway induced apoptosis of tumor cells and blocked EMT process and MMP SDF1α/CXCR4 signaling pathway inhibits the metastasis and invasion of tumor cells, induces autophagy and affects tumor metabolic reprogramming to produce anti-tumor effects. At present, the analysis of the anti-tumor mechanism of ellagic acid is slightly lacking, so this study comprehensively searched the literature on the anti-tumor mechanism of ellagic acid in various databases, reviewed the research progress of the anti-tumor effect and mechanism of ellagic acid, in order to provide reference and theoretical basis for the further development and application of ellagic acid.
Tumor-associated neutrophils (TANs) in the tumor microenvironment are prognostic biomarkers in many malignancies. However, it is unclear whether TANs can serve as a prognostic marker for clinical ...outcomes in patients with glioblastoma (GBM), as classified according to World Health Organization Classification of Tumors of the Central Nervous System, fifth edition (CNS5). In the present study, we analyzed correlations of TANs and peripheral blood neutrophils prior to radiotherapy with overall survival (OS) in GBM (CNS5).
RNA-seq expression profiles of patients with newly diagnosed GBM (CNS5) were extracted from The Cancer Genome Atlas (TCGA), and The Chinese Glioma Genome Atlas (CGGA). TAN infiltration was inferred using CIBERSORTx algorithm. Neutrophil counts prior to radiotherapy in newly diagnosed GBM (CNS5) were obtained from the First Affiliated Hospital of Fujian Medical University. The prognostic value of TANs and peripheral blood neutrophils before radiotherapy was investigated using Kaplan-Meier analysis and Cox proportional hazards models. The robustness of these findings was evaluated by sensitivity analysis, and E values were calculated.
A total of 146 and 173 individuals with GBM (CNS5) were identified from the TCGA and CGGA cohorts, respectively. High infiltration of TANs was of prognostic of poor OS in TCGA (HR = 1.621, 95% CI: 1.004-2.619) and CGGA (HR = 1.546, 95% CI: 1.029-2.323). Levels of peripheral blood neutrophils before radiotherapy (HR = 2.073, 95% CI: 1.077-3.990) were independently associated with poor prognosis. Sensitivity analysis determined that the E-value of high TANs infiltration was 2.140 and 2.465 in the TCGA and CGGA cohorts.
TANs and peripheral blood neutrophil levels before radiotherapy are prognostic of poor outcomes in GBM (CNS5).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The CrN-Ag composite coatings with various silver contents were prepared on 316L stainless steel by magnetron sputtering. The corrosion performance and antifouling properties (including anti-algae ...and antibacterial behaviors) of coatings in the artificial seawater were evaluated to give insight to potential marine applications. Results revealed that Ag-doped coatings exhibited worse corrosion resistance with increased silver, which indicated silver accelerated the reaction of the primary battery and promoted the occurrence of corrosion. However, opposite tendency was presented on anti-algae behavior. The coatings containing silver content of 13.18 at.% showed excellent anti-algae properties, and better antibacterial properties against Bacillus subtilis than Escherichia coli. The attachment of Chlorella, N. closterium and P. tricornutum on the surface of coating reduces by about 45%, 72% and 64%, respectively. The agglomerate of silver in the coatings with 18.37 at.% constrains its release and diffuse, which slowed down the corrosion reaction, embodying positive influence on corrosion resistance and negative effect on anti-algae behavior.
•Microstructure and mechanical properties of CrN-Ag coatings in different silver contents were investigated.•Anti-fouling tests of CrN-Ag coatings with different silver contents were investigated.•Silver contents and surface roughness of CrN-Ag coatings play roles in anti-fouling activities.
Pain is a distressing experience associated with tissue damage or potential tissue damage, and its occurrence is related to sensory, emotional, cognitive and social factors. Inflammatory pain is one ...of the chronic pains where pain hypersensitivity are functional features of inflammation used to protect tissues from further damage. Pain has a serious impact on people's lives and has become a social problem that cannot be ignored. MiRNAs are small non-coding RNA molecules that exert directing effects on RNA silencing by complementary binding to the 3′UTR of target mRNA. MiRNAs can target a number of protein-coding genes and participate in almost all developmental and pathological processes in animals. Growing studies have suggested that miRNAs have significant implications for inflammatory pain via participating in multiple processes during the occurrence and development, such as affecting the activation of glial cells, regulating pro-inflammatory cytokines and inhibiting central and peripheral sensitization. In this review, the advances in the role of miRNAs in inflammatory pain were discussed. miRNAs as a class of micro-mediators are potential biomarkers and therapeutic targets for inflammatory pain, which provides a better diagnostic and treatment approach for inflammatory pain.
Curcumin is a polyphenolic substance extracted from plants such as Curcuma longa, Curcuma zedoaria, and radix curcumae, and it has attracted much attention because of the anti-inflammatory, ...antioxidant, anti-tumor, antibacterial and other multiple pharmacological effects. Cervical cancer is one of the most common malignant tumors in women. With the application of HPV (human papillomavirus) vaccine, the incidence of cervical cancer is expected to be reduced, but it remains difficult to promote the vaccine among low-income population. As a commonly used food additive, curcumin has recently been found to have a significant therapeutic effect in the treatment of cervical cancer. In recent years, numerous in vitro and in vivo studies have found that curcumin can have significant efficacy in anti-cervical cancer treatment by promoting apoptosis, inhibiting tumour cell proliferation, metastasis and invasion, inhibiting HPV and inducing autophagy in tumour cells. However, due to poor water solubility, rapid catabolism, and low bioavailability of curcumin, studies on curcumin derivatives and novel formulations are increasing. Curcumin has a wide range of mechanisms of action against cervical cancer and may become a novel antitumor drug in the future, opening up new ideas for the research of curcumin in the field of antitumor. There is a lack of systematic reviews on the mechanism of action of curcumin against cervical cancer. Therefore, this study is a review of the literature based on the mechanism of action of curcumin against cervical cancer, with a view to providing reference information for scientific and clinical practitioners.
Itampolin A, a natural brominated tyrosine alkaloid isolated from the sponge Iotrochota purpurea, has been shown to have good inhibitory effects in lung cancer cells as a p38α inhibitor. A simple, ...sensitive, and reliable ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method has been established, validated, and applied to the study of the pharmacokinetics and tissue distribution of itampolin A following intragastric and intravenous administration. Itampolin A and theophylline (internal standard, IS) were extracted by the simple protein precipitation technique using methanol as the precipitating solvent. Chromatographic separation was achieved by using the optimized mobile phase of a 0.1% formic acid aqueous solution and acetonitrile in the gradient elution mode. Itampolin A and IS were detected and quantified using positive electrospray ionization in the multiple reaction monitoring mode with transitions of m/z 863.9 → 569.1 for itampolin A and m/z 181.1 → 124.1 for IS, respectively. The assay exhibited a linear dynamic range of 1–1600 ng/mL for itampolin A in biological samples and the low limit of quantification was 1 ng/mL. Non-compartmental pharmacokinetic parameters indicated that itampolin A was well-absorbed into the systemic circulation and rapidly eliminated after administration. The apparent distribution volume of itampolin A was much higher after intragastric administration than that after intravenous administration. A tissue distribution study showed that itampolin A could be detected in different tissues and maintained a high concentration in the lung, which provided a material basis for its effective application in lung cancer. The pharmacokinetic process and tissue distribution characteristics of imtapolin A were expounded in this study, which can provide beneficial information for the further research and clinical application of itampolin A.
As a prevalent and infiltrative cancer type of the central nervous system, the prognosis of lower-grade glioma (LGG) in adults is highly heterogeneous. Recent evidence has demonstrated the prognostic ...value of the mRNA expression-based stemness index (mRNAsi) in LGG. Our aim was to develop a stemness index-based signature (SI-signature) for risk stratification and survival prediction.
Differentially expressed genes (DEGs) between LGG in the Cancer Genome Atlas (TCGA) and normal brain tissue samples from the Genotype-Tissue Expression (GTEx) project were screened out, and the weighted gene correlation network analysis (WGCNA) was employed to identify the mRNAsi-related gene sets. Meanwhile, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the functional annotation of the key genes. ESTIMATE was used to calculate tumor purity for acquiring the correct mRNAsi. Differences in overall survival (OS) between the high and low mRNAsi (corrected mRNAsi) groups were compared using the Kaplan Meier analysis. By combining the Lasso regression with univariate and multivariate Cox regression, the SI-signature was constructed and validated using the Chinese Glioma Genome Atlas (CGGA).
There was a significant difference in OS between the high and low mRNAsi groups, which was also observed in the two corrected mRNAsi groups. Based on threshold limits, 86 DEGs were most significantly associated with mRNAsi via WGCNA. Seven genes (
,
,
,
,
,
, and
) were selected to establish a risk signature for primary LGG. The ROC curves showed a fair performance in survival prediction in both the TCGA and the CGGA validation cohorts. Univariate and multivariate Cox regression revealed that the risk group was an independent prognostic factor in primary LGG. The nomogram was developed based on clinical parameters integrated with the risk signature, and its accuracy for predicting 3- and 5-years survival was assessed by the concordance index, the area under the curve of the time-dependent receiver operating characteristics curve, and calibration curves.
The SI-signature with seven genes could serve as an independent predictor, and suggests the importance of stemness features in risk stratification and survival prediction in primary LGG.
Stigmasterol is a phytosterol derived from multiple herbaceous plants such as herbs, soybean and tobacco, and it has received much attention for its various pharmacological effects including ...anti-inflammation, anti-diabetes, anti-oxidization, and lowering blood cholesterol. Multiple studies have revealed that stigmasterol holds promise as a potentially beneficial therapeutic agent for malignant tumors because of its significant anti-tumor bioactivity. It is reported that stigmasterol has anti-tumor effect in a variety of malignancies (e.g., breast, lung, liver and ovarian cancers) by promoting apoptosis, inhibiting proliferation, metastasis and invasion, and inducing autophagy in tumor cells. Mechanistic study shows that stigmasterol triggers apoptosis in tumor cells by regulating the PI3K/Akt signaling pathway and the generation of mitochondrial reactive oxygen species, while its anti-proliferative activity is mainly dependent on its modulatory effect on cyclin proteins and cyclin-dependent kinase (CDK). There have been multiple mechanisms underlying the anti-tumor effect of stigmasterol, which make stigmasterol promising as a new anti-tumor agent and provide insights into research on its anti-tumor role. Presently, stigmasterol has been poorly understood, and there is a paucity of systemic review on the mechanism underlying its anti-tumor effect. The current study attempts to conduct a literature review on stigmasterol for its anti-tumor effect to provide reference for researchers and clinical workers.
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