Genetic Variants in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Bayesian Approach and Systematic Review.

A number of genome-wide association studies (GWASs) and meta-analyses of genetic variants have been performed in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We reinterpreted previous studies using false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP). This study searched publications in PubMed and Excerpta Medica Database (EMBASE) up to February 2018. Identification of noteworthy associations were analyzed using FPRP and BFDP, and data (i.e., odds ratio (OR), 95% confidence interval (CI), p-value) related to significant associations were separately extracted. Using filtered gene variants, gene ontology (GO) enrichment analysis and protein⁻protein interaction (PPI) networks were performed. Overall, 241 articles were identified, and 7 were selected for analysis. Single nucleotide polymorphisms (SNPs) discovered by GWASs were shown to be noteworthy, whereas only 27% of significant results from meta-analyses of observational studies were noteworthy. Eighty-five percent of SNPs with borderline p-values (5.0 × 10-8 < p < 0.05) in GWASs were found to be noteworthy. No overlapping SNPs were found between PR3-ANCA and MPO-ANCA vasculitis. GO analysis revealed immune-related GO terms, including "antigen processing and presentation of peptide or polysaccharide antigen via major histocompatibility complex (MHC) class II", "interferon-gamma-mediated (IFN-γ) signaling pathway". By using FPRP and BFDP, network analysis of noteworthy genetic variants discovered genetic risk factors associated with the IFN-γ pathway as novel mechanisms potentially implicated in the complex pathogenesis of ANCA-associated vasculitis

Genome-Wide Differential Methylation Profiles from Two Terpene-Rich Medicinal Plant Extracts Administered in Osteoarthritis Rats

Extracts from the plants Phlomis umbrosa and Dipsacus asperoides—which are widely used in Korean and Chinese traditional medicine to treat osteoarthritis and other bone diseases—were used to treat experimental osteoarthritis (OA) rats. Genome-wide differential methylation regions (DMRs) of these medicinal-plant-treated rats were profiled as therapeutic evidence associated with traditional medicine, and they need to be investigated further using detailed molecular research to extrapolate traditional practices to modern medicine. In total, 49 protein-encoding genes whose expression is differentially regulated during disease progression and recovery have been discovered via systematic bioinformatic analysis and have been approved/proposed as druggable targets for various bone diseases by the US food and drug administration. Genes encoding proteins involved in the PI3K/AKT pathway were found to be enriched, likely as this pathway plays a crucial role during OA progression as well as during the recovery process after treatment with the aforementioned plant extracts. The four sub-networks of PI3K/AKT were highly regulated by these plant extracts. Overall, 29 genes were seen in level 2 (51–75%) DMRs and were correlated highly with OA pathogenesis. Here, we propose that these genes could serve as targets to study OA; moreover, the iridoid and triterpenoid phytochemicals obtained from these two plants may serve as potential therapeutic agents

Transcriptional Profiles of Secondary Metabolite Biosynthesis Genes and Cytochromes in the Leaves of Four <i>Papaver</i> Species

Poppies are well-known plants in the family Papaveraceae that are rich in alkaloids. This family contains 61 species, and in this study we sequenced the transcriptomes of four species&#8217; (Papaver rhoeas, Papaver nudicaule, Papaver fauriei, and Papaver somniferum) leaves. These transcripts were systematically assessed for the expression of secondary metabolite biosynthesis (SMB) genes and cytochromes, and their expression profiles were assessed for use in bioinformatics analyses. This study contributed 265 Gb (13 libraries with three biological replicates) of leaf transcriptome data from three Papaver plant developmental stages. Sequenced transcripts were assembled into 815 Mb of contigs, including 226 Mb of full-length transcripts. The transcripts for 53 KEGG pathways, 55 cytochrome superfamilies, and benzylisoquinoline alkaloid biosynthesis (BIA) were identified and compared to four other alkaloid-rich genomes. Additionally, 22 different alkaloids and their relative expression profiles in three developmental stages of Papaver species were assessed by targeted metabolomics using LC-QTOF-MS/MS. Collectively, the results are given in co-occurrence heat-maps to help researchers obtain an overview of the transcripts and their differential expression in the Papaver development life cycle, particularly in leaves. Moreover, this dataset will be a valuable resource to derive hypotheses to mitigate an array of Papaver developmental and secondary metabolite biosynthesis issues in the future

TNF-α Pretreatment Improves the Survival and Function of Transplanted Human Neural Progenitor Cells Following Hypoxic-Ischemic Brain Injury

Neural progenitor cells (NPCs) therapy offers great promise in hypoxic-ischemic (HI) brain injury. However, the poor survival of implanted NPCs in the HI host environment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-&alpha;) is a pleiotropic cytokine that is induced in response to a variety of pathological processes including inflammation and immunity. On the other hand, TNF-&alpha; has protective effects on cell apoptosis and death and affects the differentiation, proliferation, and survival of neural stem/progenitor cells in the brain. The present study investigated whether TNF-&alpha; pretreatment on human NPCs (hNPCs) enhances the effectiveness of cell transplantation therapy under ischemic brain. Fetal brain tissue-derived hNPCs were pretreated with TNF-&alpha; before being used in vitro experiments or transplantation. TNF-&alpha; significantly increased expression of cIAP2, and the use of short hairpin RNA-mediated knockdown of cIAP2 demonstrated that cIAP2 protected hNPCs against HI-induced cytotoxicity. In addition, pretreatment of hNPCs with TNF-&alpha; mediated neuroprotection by altering microglia polarization via increased expression of CX3CL1 and by enhancing expression of neurotrophic factors. Furthermore, transplantation of TNF-&alpha;-treated hNPCs reduced infarct volume and improved neurological functions in comparison with non-pretreated hNPCs or vehicle. These findings show that TNF-&alpha; pretreatment, which protects hNPCs from HI-injured brain-induced apoptosis and increases neuroprotection, is a simple and safe approach to improve the survival of transplanted hNPCs and the therapeutic efficacy of hNPCs in HI brain injury

A Comparative Study on Physical Function Test between Faller Group and Nonfaller Group among Community-Dwelling Elderly

Keywords: aged accidental falls physical fitness s u m m a r y Purpose: This study aimed to identify the physical function test differences between the faller group and the nonfaller group in a sample of the community-dwelling elderly. Methods: This study used a nonexperimental two-group-comparative study design. The participants were 356 people aged 65 years and over living in an urban area. From May to December 2010, data were collected through personal interviews using questionnaires and measurements of muscle strength, physical endurance, flexibility, motor agility and dynamic balance, and static balance. The collected data were analyzed by descriptive statistics, Chi square analysis, and t test. Results: Upper muscle strength was significantly weaker in the faller group (p &lt; .05). Lower muscle strength was significantly weaker in the faller group; both hip flexion (p ¼ .004), knee extension (Right: p ¼ .004; Left: p ¼ .031), left ankle plantar flexion (p ¼ .045), and left ankle inversion (p ¼ .036). Tandem standing with eyes opened and closed was significantly shorter, indicating decreased static balance in the faller group. Conclusion: Nurses should make efforts to implement exercise programs focused on physical fitness enhancement for community-dwelling elderly adults for fall prevention

A Multilayered Screening Method for the Identification of Regulatory Genes in Rice by Agronomic Traits

We developed a multilayered screening method that integrates both genome and transcriptome data to effectively identify regulatory genes in rice ( Oryza sativa ). We tested our method using eight rice accessions that differed in three important nutritional and agricultural traits, anthocyanin biosynthesis, amylose content, and heading date. In the genome resequencing of eight rice accessions with 24 RNA sequencing experiments, 98% of the preprocessed reads could be uniquely mapped to the reference genome, resulting in the identification of 42,699 unique transcripts. Comparison between black and white rice cultivars showed evidence of intensive selective sweeps in chromosomes 3, 10, and 12. A total of 131 genes were differentially expressed among the black rice cultivars and found to be associated with three Gene Ontology terms (secondary metabolic process, biosynthetic process, and response to stimulus). We identified nonsynonymous Single Nucleotide Polymorphism (SNP) that likely play an important role in determining the agronomic traits differences, two upregulated and three downregulated genes in the black cultivars, and two downregulated genes in the white cultivars. The three agronomic traits were clearly grouped together by the developmental stages, regardless of any other traits, suggesting that the developmental stage is the most important factor that triggers global changes in gene expression. Interestingly, glutinous and nonglutinous black rice cultivars were distinguished from one another by different heading dates