In silico analysis reveals PRR11 as a prognostic and oncogenic marker in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common lung cancer. Although there are various treatments for LUAD, its prognosis remains poor. Therefore, it is imperative to identify new targets and develop novel therapeutic strategies. In this study, we analyze the expression of proline rich 11 (PRR11) in pan cancer based on The Cancer Genome Atlas (TCGA) database, and explore the prognostic value of PRR11 in LUAD by GEPIA2 (Gene Expression Profiling Interactive Analysis, version 2) database. In addition, the relationship between PRR11 and the clinicopathological features of LUAD was analyzed using UALCAN database. The association between PRR11 expression and immune infiltration was accessed. The PRR11 related genes were screened using LinkOmics and GEPIA2. Gene Ontology Term Enrichment (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed by David database. The results suggested that the expression of PRR11 in most tumor tissues was significantly higher than that in normal tissues. In LUAD patients, high expression of PRR11 was associated with shortened first progression survival (FPS), overall survival (OS) and post progression survival (PPS), and correlated with individual cancer stage, race, gender, smoking habit, and tissue subtype. Besides, the high expression of PRR11 was accompanied by a relatively higher infiltration level of cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cell (MDSC), and decreased infiltration level of CD8+ T cells in the tumor microenvironment. GO analyses showed that PRR11 participated in biological processes such as cell division and cell cycle, and was involved in protein binding and microtubule binding functions. KEGG analyses revealed that PRR11 was implicated in p53 signaling pathway. All the results indicated that PRR11 might be an independent prognostic biomarker and therapeutic target for LUAD.

Regulation of adipose tissue development and energy metabolism by VEGFB isoforms.

Obesity is caused by imbalanced energy intake and expenditure. Excessive energy intake and storage in adipose tissues are associated with many diseases. Several studies have demonstrated that vascular growth endothelial factor B (VEGFB) deficiency induces obese phenotypes. However, the roles of VEGFB isoforms VEGFB167 and VEGFB186 in adipose tissue development and function are still not clear. In this study, genetic mouse models of adipose-specific VEGFB167 and VEGFB186 overexpression (aP2-Vegfb167 tg/+and aP2-Vegfb186tg/+) were generated and their biologic roles were investigated. On regular chow, adipose-specific VEGFB186 is negatively associated with white adipose tissues (WATs) and positively regulates brown adipose tissues (BATs). VEGFB186 upregulates energy metabolism and metabolism-associated genes. In contrast, VEGFB167 has a nominal role in adipose development and function. On high-fat diet, VEGFB186 expression can reverse the phenotypes of VEGFB deletion. VEGFB186 overexpression upregulates BAT-associated genes and downregulates WAT-associated genes. VEGFB186 and VEGFB167 have very distinct roles in the regulation of adipose development and energy metabolism. As a key regulator of adipose tissue development and energy metabolism, VEGFB186 may be a target for obesity prevention and treatment.

Heme-heme oxygenase-2 reduces the atherosclerosis by preventing inflammation.

Objective: Heme oxygenase (HO) has been shown to have important antioxidant and anti-inflammatory properties, resulting in a vascular antitherogenic effect. This study was undertaken to evaluate the role of HO-2 in atherosclerosis. Method and results: The expression levels of HO-2 were evaluated in M1 and M2 bone marrow macrophage induced by LPS and IL4. The expression of HO-2 was significantly higher in M2 macrophage than in M1 macrophage. Western diet (WD) caused a significant increase in HO-2 expression in ApoE-/- mice. The adeno-associated viral (AAV) vectors expressing HO-2 was constructed, and the mice were received saline (ApoE-/-), AAV (ApoE-/-), AAV-HO-2 (ApoE-/-) on WD at 12 weeks and their plasma lipids, inflammatory cytokines, atherosclerosis were evaluated for 16 weeks. The results showed AAV-HO-2 was robust, with a significant decrease in the en face aortas, lipids levels, inflammatory cytokines and M1 macrophage content in AAV-HO-2 ApoE-/- compared to control AAV-ApoE-/-. Conclusion: HO-2 expression in macrophages plays an important role of the antiatherogenic effect, decreasing the inflammatory component of atherosclerotic lesions. These results suggest that HO-2 may be a novel therapeutic target for cardiovascular diseases.

Eukaryotic initiation factor 6 repression mitigates atherosclerosis progression by inhibiting macrophages expressing Fasn.

Atherosclerosis, a chronic inflammatory disease that often leads to myocardial infarction and stroke, is mainly caused by lipid accumulation. Eukaryotic initiation factor 6 (Eif6) is a rate-limiting factor in protein translation of transcription factors necessary for lipogenesis. To determine whether Eif6 affects atherosclerosis, Eif6+/- mice were crossed into Apoe-/- background. Apoe-/-/Eif6+/- mice on high fat diet showed significant reduction in atherosclerotic lesions and necrotic core content in aortic root sections in comparison with Apoe-/- mice. RNA-Seq was used to investigate the effect of Eif6 in aorta. Deficiency of Eif6 shows broad effect on cell metabolism. Expression of genes for fatty acid synthesis including Fatty acid synthase (Fasn), Elovl3, Elovl6 and Acaca are down-regulated in aortas. Importantly, Fasn is decreased in macrophages. Results suggest that Eif6 deficiency may decrease atherosclerosis through inhibition of Fasn and lipids metabolism in macrophages.

RHDV 3C protein antagonizes type I interferon signaling by cleaving interferon promoter stimulated 1 protein.

The host innate immune response to viral infection often involves the activation of type I interferons. Not surprisingly, many viruses have evolved various mechanisms to disable the interferon pathway and evade the antiviral response involving innate immunity. Rabbit hemorrhagic disease (RHD) is caused by RHD virus (RHDV), but whether it can antagonize the production of host interferon to establish infection has not been investigated. In this study, we found that during RHDV infection, the expressions of interferon and the interferon-stimulated gene were not activated. We constructed eukaryotic expression plasmids of all RHDV proteins, and found that RHDV 3C protein inhibited poly(I:C)-induced interferon expressions. Using siRNA to interfere with the expressions of TLR3 and MDA5, we found that the MDA5 signal pathway was used by the 3C protein to inhibit poly(I:C)-induced interferon expression. This effect was mediated by cleaving the interferon promoter stimulated 1 (IPS-1) protein. Finally, our study showed that interferon was effective against RHDV infection. In summary, our findings showed that the RHDV 3C protein was a new interferon antagonist. These results increase our understanding of the escape mechanism from innate immunity mediated by the RHDV 3C protein.

Pan-cancer analysis reveals DDX21 as a potential biomarker for the prognosis of multiple tumor types.

Background: DExD-box helicase 21 (DDX21) is an essential member of the RNA helicase family. DDX21 is involved in the carcinogenesis of various malignancies, but there has been no comprehensive research on its involvement in different types of cancer. Method: This study used TCGA, CPTAC, GTEx, GEO, FANTOM5, BioGRID, TIMER2, GEPIA2, cBioPortal, STRING, and Metascape databases and Survival ROC software to evaluate DDX21 gene expression, protein expression, immunohistochemistry, gene mutation, immune infiltration, and protein phosphorylation in 33 TCGA tumor types, as well as the prognostic relationship between DDX21 and different tumors, by survival analysis and similar gene enrichment analysis. Furthermore, Cell Counting Kit-8 (CCK-8) and Transwell studies were employed to assess the effect of DDX21 expression on lung adenocarcinoma (LUAD) cell proliferation and migration. Result: The DDX21 gene was highly expressed in most cancers, and overexpression was associated with poor overall survival (OS) and disease-free survival (DFS). DDX21 mutations were most common in uterine corpus endometrial carcinoma (UCEC; >5%), and DDX21 expression was positively correlated with the degree of infiltration of CAF and CD8+ cells in several tumor types. Numerous genes were co-expressed with DDX21. Gene enrichment analysis revealed close links between DDX21, RNA metabolism, and ribosomal protein production. In vitro analysis of LUAD cells showed that DDX21 expression was positively correlated with cell proliferation and migration capacity, consistent with prior bioinformatics studies. Conclusions: DDX21 is overexpressed in a variety of cancers, and overexpression in some cancers is associated with poor prognosis. Immune infiltration and DDX21-related gene enrichment analyses indicated that DDX21 may affect cancer development through mechanisms that regulate tumor immunity, RNA metabolism, and ribosomal protein synthesis. This pan-cancer study revealed the prognostic value and the oncogenic role of DDX21.

Composition of the bacterial community in the gastrointestinal tract of Kunming mice

Background: The intestinal bacterial community has an important role in maintaining human health. Dysbiosis is a key inducer of many chronic diseases including obesity and diabetes. Kunming mice are frequently used as a model of human disease and yet little is known about the bacterial microbiome resident to the gastrointestinal tract. Results: We undertook metagenomic sequencing of the luminal contents of the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum of Kunming mice. Firmicutes was the dominant bacterial phylum of each intestinal tract and Lactobacillus the dominant genus. However, the bacterial composition differed among the seven intestinal tracts of Kunming mice. Compared with the small intestine, the large intestine bacterial community of Kunming mice is more stable and diverse. Conclusions: To our knowledge, ours is the first study to systematically describe the gastrointestinal bacterial composition of Kunming mice. Our findings provide a better understanding of the bacterial composition of Kunming mice and serves as a foundation for the study of precision medicine.

Exploring the role of Mir204/211 in HNSCC by the combination of bioinformatic analysis of ceRNA and transcription factor regulation.

OBJECTIVES: This study aimed to reveal the regulatory roles of microRNAs in head and neck squamous cell carcinoma (HNSCC) through comprehensive ceRNA, miRNA-transcription factor (TF)-hub gene network and survival analysis. MATERIALS AND METHODS: Expression analysis was performed using the 'edgeR' package based on The Cancer Genome Atlas database. The ceRNA network was screened by intersecting prediction results from miRcode, miRTarBase, miRDB and TargetScan. GSE30784, GSE59102 and GSE107591 from the Gene Expression Omnibus repository were chosen for cross-validation. Hub genes were identified using a protein-protein interaction network constructed by Search Tool for the Retrieval of Interacting Genes. The Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TTRUST) was utilized to map the miRNA-TF-Hub gene network. Patient overall survival was analyzed using the 'survival' package in R. Structural and functional analysis of miR-204/211 was based on miRbase and RNAstructure. RESULTS: A ceRNA network of 178 lncRNAs, 19 miRNAs and 55 mRNAs was generated, and a TF regulatory network with 11 miRNAs, 11 TFs and 18 hub genes was constructed from the 52 hub genes identified through the protein-protein interaction (PPI) network. Survival analysis demonstrated that the dysregulated expression of 11 lncRNAs and 14 mRNAs was highly related to overall survival. Furthermore, miR-204 and miR-211 were significantly involved in the network with identical mature structures, indicating them as key miRNAs in HNSCC. CONCLUSION: This study reveals the comprehensive molecular regulatory networks centralized by miRNAs in HNSCC and uncovers the crucial role of miR-204 and miR-211, which may become potential diagnostic and therapeutic targets.

Effect of dietary concentrate to forage ratios on ruminal bacterial and anaerobic fungal populations of cashmere goats.

The rumen contains a highly complex microbial ecosystem that plays an important role in converting solar energy in plants into nutrients for ruminants and generates animal food products, such as meat and milk for humans. Therefore, understanding the effect of the dietary concentrate to forage (C:F) ratio on ruminal microbiota is of great significance for the growth and development of ruminants. In this study, changes in the ruminal bacterial and anaerobic fungal populations of Shaanbei white-cashmere (SWC) goats that were reared under different dietary C:F ratios were evaluated by high-throughput sequencing analysis. It was found that dietary C:F ratio has a significant impact on the composition of the ruminal bacteria in SWC goats. The levels of Actinobacteria and Proteobacteria were significantly increased (P < 0.05), whereas the level of Bacteroidetes was significantly decreased when the proportion of dietary concentrate was increased (P < 0.05); as the proportion of dietary concentrate increased, Prevotella, Selenomonas, and Treponema were significantly increased (P < 0.05), whereas Oscillospira and Succiniclasticum were significantly reduced (P < 0.05). Furthermore, different dietary C:F ratios significantly affected the composition of anaerobic fungi in SWC goats. As the proportion of dietary concentrate increased, Ascomycota, Basidiomycota, and Zygomycota were significantly increased (P < 0.05), while Neocallimastigomycota was significantly reduced (P < 0.05); the levels of Alternaria, Aspergillus, Neocallimastix, Orpinomyces, Piromyces, and Stachybotrys were significantly increased, while those of Candida, Penicillium, and Trichosporon were significantly decreased when the proportion of dietary concentrate increased (P < 0.05). These findings will help us to better understand the changes in ruminal bacterial and anaerobic fungal populations of SWC goats under different dietary C:F ratios, which could provide a theoretical basis for microecological regulation of SWC goats.

The Efficacy and Safety of Apatinib Treatment for Patients with Unresectable or Relapsed Liver Cancer: a retrospective study.

Purpose: Liver cancer is insensitive to chemotherapy. Sorafenib is currently the standard treatment for patients with advanced diseases, with mild survival extension and several intolerable drug-related side effects. The establishment of new treatments is an unmet clinical need. The aim of our study was to assess the efficacy and safety of apatinib, a novel antiangiogenic drug, in the treatment of patients with liver cancer. Materials and Methods: Patients with unresectable or relapsed liver cancer were included in a single center, retrospective, observational study and treated with apatinib until progressive disease or unacceptable toxicity. Results: 32 patients were reviewed from January 2015 to March 2017. No complete response (CR) occurred, 5 patients (16%) showed partial response (PR), 14 patients (44%) had stable disease (SD), 13 patients (41%) had progressive disease (PD), with disease control rate of 60%. Median progression-free survival (PFS) was 5 months (95% confidence interval [CI]: 4.3-6.1 months) for hepatocellular carcinoma (HCC) and 3 months (95% CI: 2.5-4.2 months) for intrahepatic cholangiocarcinoma (ICC). The median overall survival (OS) was 13 months (95% CI: 12.4-14.1 months) for HCC and 5 months (95% CI: 4.5-6.2 months) for ICC, respectively. The most common adverse effects (AEs) were proteinuria (31%), secondary hypertension (28%) and liver dysfunction (13%). Conclusion: Apatinib treatment was an effective for patients with liver cancer. The toxicities were mild and tolerable.

Research Progress on the Relationship between Atherosclerosis and Inflammation.

Atherosclerosis is a chronic inflammatory disease; unstable atherosclerotic plaque rupture, vascular stenosis, or occlusion caused by platelet aggregation and thrombosis lead to acute cardiovascular disease. Atherosclerosis-related inflammation is mediated by proinflammatory cytokines, inflammatory signaling pathways, bioactive lipids, and adhesion molecules. This review discusses the effects of inflammation and the systemic inflammatory signaling pathway on atherosclerosis, the role of related signaling pathways in inflammation, the formation of atherosclerosis plaques, and the prospects of treating atherosclerosis by inhibiting inflammation.

Heme oxygenase-2 suppresses acute inflammation and improves the survival of skin allografts.

The heme oxygenase (HO) system is an important regulatory arm of the intrinsic cytoprotective and anti-inflammatory system. HO-2 plays an important role in regulating inflammation following injury. The aim of this study was to evaluate the effect of HO-2 overexpression on inflammatory responses. A skin transplantation model, involving the application of skin grafts from wild-type or HO-2 overexpressing mice to BALB/c mice, was used for investigation. HO-2 overexpression suppressed the production of pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6) in macrophages compared to that in macrophages obtained from control mice. HO-2 overexpression also significantly prolonged the survival of allografted skin. Our findings suggest that HO-2 attenuates inflammatory responses and effectively prolongs skin graft survival.

Prognosis and nomogram for predicting postoperative survival of duodenal adenocarcinoma: A retrospective study in China and the SEER database.

As primary duodenal adenocarcinoma is rare, the prognostic factors of this disease remain insufficiently explored, especially in China. We identified postoperative duodenal adenocarcinoma patients at a Chinese double-center (from 2006 to 2016) or who were registered with the Surveillance, Epidemiology, and End Results (SEER) database (from 2004 to 2014). Clinicopathological features and significant prognostic factors for cancer-specific survival (CSS) were reviewed and analyzed by using univariate and multivariate Cox proportional hazards regression. Then, a nomogram predicting CSS was constructed based on the SEER database and validated externally by using the separate Chinese cohort. Totally, 137 patients from the Chinese double-center and 698 patients from the SEER database were included for analysis. The multivariate analyses showed that age, tumor grade and TNM stage were independent prognostic factors. The nomogram constructed using these factors showed a clear prognostic superiority to the AJCC-TNM classification, 7th ed. (C-index: SEER cohort, 0.693 vs 0.625, P < 0.001; Chinese cohort, 0.677 vs 0.659, P < 0.001, respectively). In summary, the valuable prognostic factors in patients with duodenal adenocarcinoma were age, tumor grade and TNM stage. This study developed a nomogram that can precisely predict the CSS for postoperative duodenal adenocarcinoma patients.

Use of green fluorescent protein to monitor Lactobacillus plantarum in the gastrointestinal tract of goats.

The experiment aimed to specifically monitor the passage of lactobacilli in vivo after oral administration. The green fluorescent protein (GFP) gene was cloned downstream from the constitutive p32 promoter from L. lactis subsp. cremoris Wg2. The recombinant expression vector, pLEM415-gfp-p32, was electroporated into Lactobacillus plantarum (L. plantarum) isolated from goat. Green fluorescent protein (GFP) was successfully expressed in L. plantarum. After 2 h post-administration, transformed Lactobacillus could be detectable in all luminal contents. In the rumen, bacteria concentration initially decreased, reached the minimum at 42 h post-oral administration and then increased. However, this concentration decreased constantly in the duodenum. This result indicated that L. plantarum could colonize in the rumen but not in the duodenum.

Use of green fluorescent protein to monitor Lactobacillus plantarum in the gastrointestinal tract of goats

The experiment aimed to specifically monitor the passage of lactobacilli in vivo after oral administration. The green fluorescent protein (GFP) gene was cloned downstream from the constitutive p32 promoter from L. lactis subsp. cremoris Wg2. The recombinant expression vector, pLEM415-gfp-p32, was electroporated into Lactobacillus plantarum (L. plantarum) isolated from goat. Green fluorescent protein (GFP) was successfully expressed in L. plantarum. After 2 h post-administration, transformed Lactobacillus could be detectable in all luminal contents. In the rumen, bacteria concentration initially decreased, reached the minimum at 42 h post-oral administration and then increased. However, this concentration decreased constantly in the duodenum. This result indicated that L. plantarum could colonize in the rumen but not in the duodenum.

Rumen bacterial diversity of 80 to 110-day-old goats using 16S rRNA sequencing.

The ability of rumen microorganisms to use fibrous plant matter plays an important role in ruminant animals; however, little information about rumen colonization by microbial populations after weaning has been reported. In this study, high-throughput sequencing was used to investigate the establishment of this microbial population in 80 to 110-day-old goats. Illumina sequencing of goat rumen samples yielded 101,356,610 nucleotides that were assembled into 256,868 reads with an average read length of 394 nucleotides. Taxonomic analysis of metagenomic reads indicated that the predominant phyla were distinct at different growth stages. The phyla Firmicutes and Synergistetes were predominant in samples taken from 80 to 100-day-old goats, but Bacteroidetes and Firmicutes became the most abundant phyla in samples from 110-day-old animals. There was a remarkable variation in the microbial populations with age; Firmicutes and Synergistetes decreased after weaning, but Bacteroidetes and Proteobacteria increased from 80 to 110 day of age. These findings suggested that colonization of the rumen by microorganisms is related to their function in the rumen digestive system. These results give a better understanding of the role of rumen microbes and the establishment of the microbial population, which help to maintain the host's health and improve animal performance.

Multi-voxel pattern analysis of selective representation of visual working memory in ventral temporal and occipital regions.

While previous results from univariate analysis showed that the activity level of the parahippocampal gyrus (PHG) but not the fusiform gyrus (FG) reflects selective maintenance of the cued picture category, present results from multi-voxel pattern analysis (MVPA) showed that the spatial response patterns of both regions can be used to differentiate the selected picture category in working memory. The ventral temporal and occipital areas including the PHG and FG have been shown to be specialized in perceiving and processing different kinds of visual information, though their role in the representation of visual working memory remains unclear. To test whether the PHG and FG show spatial response patterns that reflect selective maintenance of task-relevant visual working memory in comparison with other posterior association regions, we reanalyzed data from a previous fMRI study of visual working memory with a cue inserted during the delay period of a delayed recognition task. Classification of FG and PHG activation patterns for the selected category (face or scene) during the cue phase was well above chance using classifiers trained with fMRI data from the cue or probe phase. Classification of activity in other temporal and occipital regions for the cued picture category during the cue phase was relatively less consistent even though classification of their activity during the probe recognition was comparable with the FG and PHG. In sum, these findings suggest that the FG and PHG carry information relevant to the cued visual category, and their spatial activation patterns during selective maintenance seem to match those during visual recognition.