Selenium Status in Patients with Chronic Liver Disease: A Systematic Review and Meta-Analysis

Background: The potential role of selenium in preventing chronic liver diseases remains controversial. This meta-analysis aimed to summarize the available evidence from observational studies and intervention trials that had evaluated the associations between body selenium status and chronic liver diseases. Methods: We comprehensively searched MEDLINE, Embase, Web of Science, and Cochrane Library from inception to April 2021. The study protocol was registered at PROSPERO (CRD42020210144). Relative risks (RR) for the highest versus the lowest level of selenium and standard mean differences (SMD) with 95% confidence intervals (CI) were pooled using random-effects models. Heterogeneity and publication bias were evaluated using the I2 statistic and Egger’s regression test, respectively. Results: There were 50 studies with 9875 cases and 12975 population controls in the final analysis. Patients with hepatitis (SMD = −1.78, 95% CI: −2.22 to −1.34), liver cirrhosis (SMD = −2.06, 95% CI: −2.48 to −1.63), and liver cancer (SMD = −2.71, 95% CI: −3.31 to −2.11) had significantly lower selenium levels than controls, whereas there was no significant difference in patients with fatty liver diseases (SMD = 1.06, 95% CI: −1.78 to 3.89). Moreover, the meta-analysis showed that a higher selenium level was significantly associated with a 41% decrease in the incidence of significant advanced chronic liver diseases (RR = 0.59, 95% CI: 0.49 to 0.72). Conclusion: Our meta-analysis suggested that both body selenium status and selenium intake were negatively associated with hepatitis, cirrhosis, and liver cancer. However, the associations for fatty liver diseases were conflicting and need to be established in prospective trials

Overview of the Large-Scale Biosphere–Atmosphere Experiment in Amazonia Data Model Intercomparison Project (LBA-DMIP)

A fundamental question connecting terrestrial ecology and global climate change is the sensitivity of key terrestrial biomes to climatic variability and change. The Amazon region is such a key biome: it contains unparalleled biological diversity, a globally significant store of organic carbon, and it is a potent engine driving global cycles of water and energy. The importance of understanding how land surface dynamics of the Amazon region respond to climatic variability and change is widely appreciated, but despite significant recent advances, large gaps in our understanding remain. Understanding of energy and carbon exchange between terrestrial ecosystems and the atmosphere can be improved through direct observations and experiments, as well as through modeling activities. Land surface/ecosystem models have become important tools for extrapolating local observations and understanding to much larger terrestrial regions. They are also valuable tools to test hypothesis on ecosystem functioning. Funded by NASA under the auspices of the LBA (the Large-Scale Biosphere–Atmosphere Experiment in Amazonia), the LBA Data Model Intercomparison Project (LBA-DMIP) uses a comprehensive data set from an observational network of flux towers across the Amazon, and an ecosystem modeling community engaged in ongoing studies using a suite of different land surface and terrestrial ecosystem models to understand Amazon forest function. Here an overview of this project is presented accompanied by a description of the measurement sites, data, models and protocol

Regulation of early diagnosis and prognostic markers of lung adenocarcinoma in immunity and hypoxia

Abstract Lung adenocarcinoma is still cancer with the highest mortality. Hypoxia and immunity play an essential role in the occurrence and development of tumors. Therefore, this study is mainly to find new early diagnosis and prognosis markers and explore the relationship among the markers and immunity and hypoxia, to improve the prognosis of patients. Firstly, based on the clinical database in TCGA, we determined the most critical clinicopathological parameters affecting the prognosis of patients through a variety of analysis methods. According to pathological parameters, logistic most minor absolute contraction selection operator (lasso), univariate and multivariate regression analysis, the risk genes related to early prognosis were screened, and the risk model was established. Then, in different risk groups, GSEA and CIBERSORT algorithms were used to analyze the distribution and enrichment of the immune cells and hypoxia, to study the effects of early prognostic indicators on hypoxia and immunity. At the same time, we analyzed the different levels of risk genes in normal cells (BSEA-2B) and tumor cells (H1299, A549, PC9, and H1975). Finally, A549 and PC9 cells were induced by CoCl2 to establish a hypoxic environment, and the correlation between risk genes and HIF1A was analyzed. The risk model based on risk genes (CYP4B1, KRT6A, and FAM83A) was accurate and stable for the prognosis of patients. It is closely related to immunity and hypoxia. In BSEA-2B cells, the mRNA and protein expression of CYP4B1 was higher, while the expression of KRT6A and FAM83A was lower. Finally, we found that FAM83A and HIF1A showed a significant positive correlation when A549 and PC9 cells were exposed to hypoxia. The discovery of early diagnostic markers related to immunity, hypoxia, and prognosis, provides a new idea for early screening and prognostic treatment of lung adenocarcinoma

Predicting lung adenocarcinoma prognosis, immune escape, and pharmacomic profile from arginine and proline-related genes

Abstract Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that ranks first in morbidity and mortality. Abnormal arginine metabolism is associated with inflammatory lung disease and may influence alterations in the tumor immune microenvironment. However, the potential role of arginine and proline metabolic patterns and immune molecular markers in LUAD is unclear. Gene expression, somatic mutations, and clinicopathological information of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was performed to identify metabolic genes associated with overall survival (OS). Unsupervised clustering divided the sample into two subtypes with different metabolic and immunological profiles. Gene set enrichment analysis (GESA) and gene set variation analysis (GSVA) were used to analyze the underlying biological processes of the two subtypes. Drug sensitivity between subtypes was also predicted; then prognostic features were developed by multivariate Cox regression analysis. In addition, validation was obtained in the GSE68465, and GSE50081 dataset. Then, gene expression, and clinical characterization of hub genes CPS1 and SMS were performed; finally, in vitro validation experiments for knockdown of SMS were performed in LUAD cell lines. In this study, we first identified 12 arginine and proline-related genes (APRGs) significantly associated with OS and characterized the clinicopathological features and tumor microenvironmental landscape of two different subtypes. Then, we established an arginine and proline metabolism-related scoring system and identified two hub genes highly associated with prognosis, namely CPS1, and SMS. In addition, we performed CCK8, transwell, and other functional experiments on SMS to obtain consistent results. Our comprehensive analysis revealed the potential molecular features and clinical applications of APRGs in LUAD. A model based on 2 APRGs can accurately predict survival outcomes in LUAD, improve our understanding of APRGs in LUAD, and pave a new pathway to guide risk stratification and treatment strategy development for LUAD patients

PBK correlates with prognosis, immune escape and drug response in LUAD

Abstract PBK (PDZ-binding kinase) is a protein-coding gene that encodes a serine/threonine protein kinase associated with the dual-specific mitogen-activated protein kinase (MAPKK) family. Overexpression of this gene is closely linked to tumor development. In this study, we aimed to investigate the role of PBK in lung adenocarcinoma (LUAD) progression, prognosis, and immune evasion. We conducted a pan-cancer analysis of PBK to examine its expression and prognostic value. In the LUAD cohort, we analyzed PBK expression, prognosis, mutational features, and immune infiltration in groups with different PBK expression levels. We constructed a PBK-associated genomic model, integrated it into a nomogram, and compared high and low-risk subgroups. In our pan-cancer analysis, PBK was significantly upregulated, particularly in LUAD patients, and displayed poor prognosis. The high PBK expression group had many deletion mutations but still showed gene upregulation. Immune infiltration analysis indicated that PBK-triggered immune escape in the high expression group might relate to antigen presentation, dendritic cell, and CD8+ T cell infiltration. We constructed a 5-gene prognostic model and a nomogram to quantify individual survival probabilities. The PBK-associated gene prognostic model reliably predicted patient prognosis and drug response. Our findings offer new insights into PBK-induced immune escape and targeted therapy during LUAD development, providing valuable suggestions for clinical treatment approaches

Leptin Stimulates Prolactin mRNA Expression in the Goldfish Pituitary through a Combination of the PI3K/Akt/mTOR, MKK3/6/p38MAPK and MEK1/2/ERK1/2 Signalling Pathways

Leptin actions at the pituitary level have been extensively investigated in mammalian species, but remain insufficiently characterized in lower vertebrates, especially in teleost fish. Prolactin (PRL) is a pituitary hormone of central importance to osmoregulation in fish. Using goldfish as a model, we examined the global and brain-pituitary distribution of a leptin receptor (lepR) and examined the relationship between expression of lepR and major pituitary hormones in different pituitary regions. The effects of recombinant goldfish leptin-AI and leptin-AII on PRL mRNA expression in the pituitary were further analysed, and the mechanisms underlying signal transduction for leptin-induced PRL expression were determined by pharmacological approaches. Our results showed that goldfish lepR is abundantly expressed in the brain-pituitary regions, with highly overlapping PRL transcripts within the pituitary. Recombinant goldfish leptin-AI and leptin-AII proteins could stimulate PRL mRNA expression in dose- and time-dependent manners in the goldfish pituitary, by both intraperitoneal injection and primary cell incubation approaches. Moreover, the PI3K/Akt/mTOR, MKK3/6/p38MAPK, and MEK1/2/ERK1/2—but not JAK2/STAT 1, 3 and 5 cascades—were involved in leptin-induced PRL mRNA expression in the goldfish pituitary

Prrx1 promotes stemness and angiogenesis via activating TGF-β/smad pathway and upregulating proangiogenic factors in glioma

Abstract Glioma is one of the most lethal cancers with highly vascularized networks and growing evidences have identified glioma stem cells (GSCs) to account for excessive angiogenesis in glioma. Aberrant expression of paired-related homeobox1 (Prrx1) has been functionally associated with cancer stem cells including GSCs. In this study, Prrx1 was found to be markedly upregulated in glioma specimens and elevated Prrx1 expression was inversely correlated with prognosis of glioma patients. Prrx1 potentiated stemness acquisition in non-stem tumor cells (NSTCs) and stemness maintenance in GSCs, accompanied with increased expression of stemness markers such as SOX2. Prrx1 also promoted glioma angiogenesis by upregulating proangiogenic factors such as VEGF. Consistently, silencing Prrx1 markedly inhibited glioma proliferation, stemness, and angiogenesis in vivo. Using a combination of subcellular proteomics and in vitro analyses, we revealed that Prrx1 directly bound to the promoter regions of TGF-β1 gene, upregulated TGF-β1 expression, and ultimately activated the TGF-β/smad pathway. Silencing TGF-β1 mitigated the malignant behaviors induced by Prrx1. Activation of this pathway cooperates with Prrx1 to upregulate the expression of stemness-related genes and proangiogenic factors. In summary, our findings revealed that Prrx1/TGF-β/smad signal axis exerted a critical role in glioma stemness and angiogeneis. Disrupting the function of this signal axis might represent a new therapeutic strategy in glioma patients