Additional file 1 of Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis

Additional file 1

DataSheet_1_The causal association between bone mineral density and risk of osteoarthritis: A Mendelian randomization study.docx

ObjectivesThe causal direction and magnitude of the association between total body bone mineral density (TB-BMD) and osteoarthritis (OA) risk is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. The study aimed to explore the relationships between TB-BMD concentration and OA using Mendelian randomization (MR).MethodsIn this study, we used two-sample MR to obtain unconfounded estimates of the effect of TB-BMD on hip and knee OA. Single nucleotide polymorphisms (SNPs) strongly associated with TB-BMD in a large genome-wide association study (GWAS) were identified and selected as instrumental variables (IVs). In addition to the main analysis using inverse-variance weighted (IVW) method, we applied 2 additional methods to control for pleiotropy(MR-Egger regression, weighted median estimator) and compared the respective MR estimates.ResultsMR analyses suggested that genetically predicted higher TB-BMD is associated with risks of hip OA (For IVW: OR=1.199, 95%CI: 1.02-1.42, P=0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, P=0.002). There was no evidence that the observed causal effect between TB-BMD and the risk of hip OA was affected by genetic pleiotropy(P=0.618). Additionally, our study didn’t support causal effects of a genetically increased TB-BMD risk on knee OA risk(OR=1.121, 95%CI: 0.99-1.28, P=0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, P=0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, P=0.217 using MR-Egger).ConclusionsOur findings support a causal effect that a genetic predisposition to systematically higher TB-BMD was associated with the risk of OA. And, TB-BMD likely exerts an effect on the risk of hip OA not knee OA.</p

DataSheet_2_The causal association between bone mineral density and risk of osteoarthritis: A Mendelian randomization study.docx

ObjectivesThe causal direction and magnitude of the association between total body bone mineral density (TB-BMD) and osteoarthritis (OA) risk is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. The study aimed to explore the relationships between TB-BMD concentration and OA using Mendelian randomization (MR).MethodsIn this study, we used two-sample MR to obtain unconfounded estimates of the effect of TB-BMD on hip and knee OA. Single nucleotide polymorphisms (SNPs) strongly associated with TB-BMD in a large genome-wide association study (GWAS) were identified and selected as instrumental variables (IVs). In addition to the main analysis using inverse-variance weighted (IVW) method, we applied 2 additional methods to control for pleiotropy(MR-Egger regression, weighted median estimator) and compared the respective MR estimates.ResultsMR analyses suggested that genetically predicted higher TB-BMD is associated with risks of hip OA (For IVW: OR=1.199, 95%CI: 1.02-1.42, P=0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, P=0.002). There was no evidence that the observed causal effect between TB-BMD and the risk of hip OA was affected by genetic pleiotropy(P=0.618). Additionally, our study didn’t support causal effects of a genetically increased TB-BMD risk on knee OA risk(OR=1.121, 95%CI: 0.99-1.28, P=0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, P=0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, P=0.217 using MR-Egger).ConclusionsOur findings support a causal effect that a genetic predisposition to systematically higher TB-BMD was associated with the risk of OA. And, TB-BMD likely exerts an effect on the risk of hip OA not knee OA.</p

Additional file 1: of Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials

Table S1. The results of sensitivity analysis. Figure S1. Summary of study search and selection. RCT randomized controlled trail. Figure S2. Plots of bias risk. Figure S3. Funnel plot of effect size. (DOCX 4698 kb

Image_1_Identification of AIDS-Associated Kaposi Sarcoma: A Functional Genomics Approach.tif

BackgroundKaposi sarcoma-associated herpes virus (KSHV) is one of the most common causal agents of Kaposi Sarcoma (KS) in individuals with HIV-infections. The virus has gained attention over the past few decades due to its remarkable pathogenic mechanisms. A group of genes, ORF71, ORF72, and ORF73, are expressed as polycistronic mRNAs and the functions of ORF71 and ORF72 in KSHV are already reported in the literature. However, the function of ORF73 has remained a mystery. The aim of this study is to conduct comprehensive exploratory experiments to clarify the role of ORF73 in KSHV pathology and discover markers of AIDS-associated KSHV-induced KS by bioinformatic approaches.Methods and ResultsWe searched for homologues of ORF-73 and attempted to predict protein-protein interactions (PPI) based on GeneCards and UniProtKB, utilizing Position-Specific Iterated BLAST (PSI-BLAST). We applied Gene Ontology (GO) and KEGG pathway analyses to identify highly conserved regions between ORF-73 and p53to help us identify potential markers with predominant hits and interactions in the KEGG pathway associated with host apoptosis and cell arrest. The protein p53 is selected because it is an important tumor suppressor antigen. To identify the potential roles of the candidate markers at the molecular level, we used PSIPRED keeping the conserved domains as the major parameters to predict secondary structures. We based the FUGE interpretation consolidations of the sequence-structure comparisons on distance homology, where the score for the amino acids matching the insertion/deletion (indels) detected were based on structures compared to the FUGE database of structural profiles. We also calculated the compatibility scores of sequence alignments accordingly. Based on the PSI-BLAST homologues, we checked the disordered structures predicted using PSI-Pred and DISO-Pred for developing a hidden Markov model (HMM). We further applied these HMMs models based on the alignment of constructed 3D models between the known structure and the HMM of our sequence. Moreover, stable homology and structurally conserved domains confirmed that ORF-73 maybe an important prognostic marker for AIDS-associated KS.ConclusionCollectively, similar variants of ORF-73 markers involved in the immune response may interact with targeted host proteins as predicted by our computational analysis. This work also suggests the existence of potential conformational changes that need to be further explored to help elucidate the role of immune signaling during KS towards the development of therapeutic applications.</p

Cyanobacteria produce AEG [N-(<i>2</i>-aminoethyl)glycine], both in axenic PCC strains and environmental samples.

<p>Using triple quadrupole LC-MS/MS analysis, AEG was identified using a precursor ion <i>m/z</i> 459 and selective reaction monitoring of four transitions <i>m/z</i> 459 to <i>m/z</i> 289 (top pane), <i>m/z</i> 214 (second pane), <i>m/z</i> 171 (third pane), and <i>m/z</i> 119 (bottom pane). a, AEG was detected as a free or weakly bound compound in axenic <i>Nostoc</i> PCC 7120. b, A synthetic AEG standard. c, AEG in an extract of bound compounds from an environmental cyanobacterial sample collected at Benson Marina, Logan, Utah, USA.</p

Forest plot of OR with 95%CI for the <i>HOTAIR</i> rs1899663 with cancer risk under dominant model.

<p>Forest plot of OR with 95%CI for the <i>HOTAIR</i> rs1899663 with cancer risk under dominant model.</p

Quantitative Assessment of the Polymorphisms in the <i>HOTAIR</i> lncRNA and Cancer Risk: A Meta-Analysis of 8 Case-Control Studies

<div><p>HOX transcript antisense intergenic RNA (<i>HOTAIR</i>) is a long non-coding RNA (lncRNA) that functions as an oncogenic molecule in different cancer cells. Genetic variants of <i>HOTAIR</i> may affect the activity of certain regulatory factors and further regulate the aberrant expression of <i>HOTAIR</i>, which might be underlying mechanisms that affect tumour susceptibility and prognosis. Recently, several studies have been performed to examine the possible link between polymorphisms in <i>HOTAIR</i> and cancer risk; however, the results have been inconclusive. Therefore, we performed a meta-analysis to estimate the associations between <i>HOTAIR</i> polymorphisms (rs920778, rs4759314 and rs1899663) and cancer risk. Eight studies comprising 7,151 cases and 8,740 controls were included in our study. Overall, no significant associations between the <i>HOTAIR</i> polymorphisms (rs920778, rs4759314 and rs1899663) and cancer risk were observed. However, in further stratified analyses, the variant T allele of rs920778 exhibited a significant increased risk of developing digestive cancers (dominant model: OR = 1.44; 95% CI = 1.31–1.59). These findings provided evidence that <i>HOTAIR</i> rs920778 may modify the susceptibility to certain cancer types. Further studies incorporating subjects with different ethnic backgrounds combined with re-sequencing of the marked region and functional evaluations are warranted.</p></div

Microphotographs of the field culture <i>Leptolyngbya</i> sp./Naviculales.

<p>(<b>a</b>) untreated culture; (<b>b</b>) germanium dioxide-treated culture.</p

Quantification of BMAA in diatoms.

<p>Mean of BMAA concentration (±STD) in different samples of diatoms.</p><p><i>n</i>: Biological replicates.</p