Elevated LILRB1 expression predicts poor prognosis and is associated with tumor immune infiltration in patients with glioma.

BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) is regarded as an inhibitory molecule. However, the importance of LILRB1 expression in glioma has not yet been determined. This investigation examined the immunological signature, clinicopathological importance and prognostic value of LILRB1 expression in glioma. METHODS: We used data from the UCSC XENA database, the Cancer Genome Atlas (TCGA) database, the Chinese Glioma Genome Atlas (CGGA) database, the STRING database, the MEXPRESS database and our clinical glioma samples to perform bioinformatic analysis and used vitro experiments to examine the predictive value and potential biological roles of LILRB1 in glioma. RESULTS: Higher LILRB1 expression was considerably present in the higher WHO grade glioma group and was linked to a poorer prognosis in patients with glioma. Gene set enrichment analysis (GSEA) revealed that LILRB1 was positively correlated with the JAK/STAT signaling pathway. LILRB1 combined with tumor mutational burden (TMB) and microsatellite instability (MSI) may be a promising indicator for the effectiveness of immunotherapy in patients with glioma. Increased LILRB1 expression was positively linked with the hypomethylation, M2 macrophage infiltration, immune checkpoints (ICPs) and M2 macrophage makers. Univariate and multivariate Cox regression analyses determined that increased LILRB1 expression was a standalone causal factor for glioma. Vitro experiments determined that LILRB1 positively enhanced the proliferation, migration and invasion in glioma cells. MRI images demonstrated that higher LILRB1 expression was related with larger tumor volume in patients with glioma. CONCLUSION: Dysregulation of LILRB1 in glioma is correlated with immune infiltration and is a standalone causal factor for glioma.

Association between 23 drugs and Parkinson's disease: A two-sample Mendelian randomization study.

BACKGROUND: Parkinson's disease (PD) is a common degenerative nervous system disease. At present, there are certain limitations in various treatment options aimed at preventing or delaying the progression of PD. Therefore, the exploration of new drugs for PD is beneficial. Mendelian randomization (MR) analysis can be used to explore the association between drugs and diseases. In this study, MR analysis was adopted to investigate the causal relationship between 23 drugs and PD. These drugs have been approved for the treatment of different diseases, such as salicylic acid and derivatives (collectively called salicylates, e.g., aspirin, used for fever and pain relief), antithrombotic agents (e.g., warfarin, aspirin, used for preventing thrombotic events). METHODS: The GWAS data for the 23 drugs were obtained from the UK Biobank (UKB) project, while the GWAS data for PD were sourced from FinnGen. Single-Nucleotide Polymorphisms (SNPs) were selected as instrumental variables (IVs). We first performed a series of quality control steps (including MR-PRESSO) to select the appropriate SNPs. Two-sample MR analysis was performed using five different methods, including inverse variance weighting (IVW) with random-effects model, weighted median, MR-Egger, simple model, and weighted model. At the same time, sensitivity analysis was carried out using the MR-Egger and Cochran's Q test to ensure the authenticity and reliability of the results. RESULTS: In MR-PRESSO, salicylates and antithrombotic agents showed statistically significant associations with PD, respectively. In the main MR analysis (IVW), there was a negative causal relationship between salicylates and PD (OR = 0.73, 95% CI = 0.54-0.98, p = .039). Similarly, there was a negative causal relationship between antithrombotic agents and PD (OR = 0.70, 95%CI = 0.52-0.96, p = .027). No statistically significant association was found between the remaining 21 drugs and PD. CONCLUSION: This MR study demonstrated that salicylates and antithrombotic agents can reduce the risk of PD, thus providing a novel avenue for future drug exploration in PD.

GPR37 expression as a prognostic marker in gliomas: a bioinformatics-based analysis.

BACKGROUND: Gliomas are the most frequently diagnosed primary brain tumors, and are associated with multiple molecular aberrations during their development and progression. GPR37 is an orphan G protein-coupled receptor (GPCR) that is implicated in different physiological pathways in the brain, and has been linked to various malignancies. The aim of this study was to explore the relationship between GPR37 gene expression and the clinicopathological factors, patient prognosis, tumor-infiltrating immune cell signature GSEA and methylation levels in glioma. METHODS: We explored the diagnostic value, clinical relevance, and molecular function of GPR37 in glioma using TCGA, STRING, cBioPortal, Tumor Immunity Estimation Resource (TIMER) database and MethSurv databases. Besides, the "ssGSEA" algorithm was conducted to estimate immune cells infiltration abundance, with 'ggplot2' package visualizing the results. Immunohistochemical staining of clinical samples were used to verify the speculations of bioinformatics analysis. RESULTS: GPR37 expression was significantly higher in the glioma tissues compared to the normal brain tissues, and was linked to poor prognosis. Functional annotation of GPR37 showed enrichment of ether lipid metabolism, fat digestion and absorption, and histidine metabolism. In addition, GSEA showed that GPR37 was positively correlated to the positive regulation of macrophage derived foam cell differentiation, negative regulation of T cell receptor signaling pathway, neuroactive ligand receptor interaction, calcium signaling pathway, and negatively associated with immunoglobulin complex, immunoglobulin complex circulating, ribosome and spliceosome mediated by circulating immunoglobulin etc. TIMER2.0 and ssGSEA showed that GPR37 expression was significantly associated with the infiltration of T cells, CD8 T cell, eosinophils, macrophages, neutrophils, NK CD56dim cells, NK cells, plasmacytoid DCs (pDCs), T helper cells and T effector memory (Tem) cells. In addition, high GPR37 expression was positively correlated with increased infiltration of M2 macrophages, which in turn was associated with poor prognosis. Furthermore, GPR37 was positively correlated with various immune checkpoints (ICPs). Finally, hypomethylation of the GPR37 promoter was associated with its high expression levels and poor prognosis in glioma. CONCLUSION: GPR37 had diagnostic and prognostic value in glioma. The possible biological mechanisms of GPR37 provide novel insights into the clinical diagnosis and treatment of glioma.

[Nutrient resorption patterns of Phragmites australis leaves and its response to soil moisture in Yangguan wetland, Dunhuang, Northwest China]. / æ•¦ç Œé˜³å ³æ¹¿åœ°èŠ¦è‹‡å¶ç‰‡å »åˆ†é‡å¸æ”¶æ¨¡å¼åŠå ¶å¯¹åœŸå£¤æ°´åˆ†çš„å“åº”.

Nutrient resorption of leaves is an important nutrient conservation mechanism for plants in nutrient-poor habitats. Understanding the responses of leaf nutrient resorption to soil moisture is helpful to reveal the adaptation strategies of plants to the environment. In this study, the dominant plant in the Yangguang wetland of Dunhuang Phragmites australis was used as research material, to explore nitrogen and phosphorus resorption patterns of P. australis leaves and their responses to soil moisture under different moisture regimes, i.e. high (33.5%±1.9%), medium (26.4%±1.3%) and low (11.3%±1.5%). The results showed that: 1) With the decreases of soil moisture, soil N concentration decreased significantly, and N concentrations in mature and senescent leaves increased significantly, the P concentration in mature and senescent leaves as well as in soil did not change. 2) N resorption efficiency of leaves under high moisture condition was 76.1%, which was significantly higher than the medium (65.5%) and low (62.5%) moisture conditions. P resorption efficiency varied among different moisture conditions. 3) The N concentrations of mature and senescent leaves were negatively correlated with N resorption efficiency. There was no significant correlation between P concentration and P resorption efficiency in mature leaves, but the P concentration of senescent leaves was negatively correlated with P resorption efficiency of leaves. As a result, water scarcity is not conducive to leaf N resorption.