Plasminogen Activator Inhibitor-1 and Adiponectin Are Associated With Metabolic Syndrome Components.

BACKGROUND: We aimed to study the associations of adipocytokines, endothelial damage markers, and high-sensitivity C-reactive protein (hs-CRP) with metabolic syndrome (MetS) components. METHODS: This cross-sectional study included 202 subjects categorized into MetS and No-MetS according to Harmonizing Adult Treatment Panel III. RESULTS: Subjects with MetS showed higher levels of proinflammatory molecules but significantly lower adiponectin levels than subjects with No-MetS. Among the studied adipocytokines, plasminogen activator inhibitor-1 (PAI-1) and adiponectin showed the strongest associations with most MetS components. PAI-1 was associated with MetS (odds ratio (OR) 1.107 (1.065-1.151), P < 0.0001), whereas adiponectin was inversely associated with MetS (OR 0.710 (0.610-0.825), P < 0.0001). Following adjustment by sex, age, body mass index, and 24-hour urinary sodium excretion in a multivariate analysis, the association of PAI-1 (OR 1.090 (1.044-1.137), P < 0.0001) and adiponectin (OR 0.634 (0.519-0.775), P < 0.0001) with MetS remained significant. Multivariate analyses supported a model in which systolic blood pressure (BP) could be predicted by PAI-1, hs-CRP, and matrix metalloproteinase 2 (R2 = 0.125; P = 0.04); diastolic BP (R2 = 0.218; P = 0.0001) and glucose (R2 = 0.074; P = 0.0001) could be predicted by PAI-1; waist circumference could be predicted by PAI-1 and hs-CRP (R2 = 0.28; P = 0.016). Receiver operating characteristic curve analysis showed that a PAI-1 concentration had the best sensitivity and specificity for discriminating subjects with MetS. CONCLUSION: PAI-1 and adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk.

Temporal Gene Expression Signature of Plasma Extracellular Vesicles-MicroRNAs from Post-Smolt Coho Salmon Challenged with Piscirickettsia salmonis.

Piscirickettsiosis is the most important bacterial disease in the Chilean salmon industry, which has borne major economic losses due to failure to control it. Cells use extracellular vesicles (EVs) as an inter-cellular communicators to deliver several factors (e.g., microRNAs) that may regulate the responses of other cells. However, there is limited knowledge about the identification and characterization of EV-miRNAs in salmonids or the effect of infections on these. In this study, Illumina sequencing technology was used to identify Coho salmon plasma EV-miRNAs upon Piscirickettsia salmonis infection at four different time points. A total of 118 novels and 188 known EV-miRNAs, including key immune teleost miRNAs families (e.g., miR-146, miR-122), were identified. A total of 245 EV-miRNAs were detected as differentially expressed (FDR < 5%) in terms of control, with a clear down-regulation pattern throughout the disease. KEGG enrichment results of EV-miRNAs target genes showed that they were grouped mainly in cellular, stress, inflammation and immune responses. Therefore, it is hypothesized that P. salmonis could potentially benefit from unbalanced modulation response of Coho salmon EV-miRNAs in order to promote a hyper-inflammatory and compromised immune response through the suppression of different key immune host miRNAs during the course of the infection, as indicated by the results of this study.

Temporal genome-wide DNA methylation signature of post-smolt Pacific salmon challenged with Piscirickettsia salmonis.

Piscirickettsiosis is the most important bacterial disease in the Chilean salmon industry, which has sorted several efforts to its control, generating enormous economic losses. Epigenetic alterations, such as DNA methylation, can play a relevant role in the modulation of the metazoans response to pathogens. Bacterial disease may activate global and local immune responses generating intricate responses with significant biological impact in the host. However, it is scarcely understood how bacterial infections influence fish epigenetic alterations. In the present study, we utilized Pacific salmon and Piscirickettsiosis as model, to gain understanding into the dynamics of DNA methylation among fish-bacterial infection interactions. A genome-wide analysis of DNA methylation patterns in female spleen tissue of Pacific salmon was achieved by reduced representation bisulphite sequencing from a time course design. We determined 2,251, 1,918, and 2,516 differentially methylated regions DMRs among infected and control Pacific salmon in 1 dpi, 5 dpi, and 15 dpi, respectively. The mean methylation difference per DMR among control and infected groups was of ~35%, with an oscillatory pattern of hypo, hyper, and hypomethylation across the disease. DMCs, among the control and infected group, showed that they were statistically enriched in intergenic regions and depleted in exons. Functional annotation of the DMR genes demonstrated three KEGG principal categories, associated directly with the host response to pathogens infections. Our results provide the first evidence of epigenetic variation in fish provoked by bacterial infection and demonstrate that this variation can be modulated across the disease.

Identification and characterization of miRNAs and lncRNAs of coho salmon (Oncorhynchus kisutch) in normal immune organs.

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two relevant non-coding RNAs (ncRNAs) class. Oncorhynchus kisutch (coho salmon) is an important aquaculture pacific salmon species without report of miRNAs and a very limited register of lncRNAs. To gain knowledge about the interaction and discovery of miRNAs and lncRNAs in coho salmon we used high-throughput sequencing technology to sequence small and transcriptome libraries from three immune organs. A total of 163 mature miRNAs and 4,975 lncRNAs were discovered. The profiles of expression of both ncRNAs indicated that liver and head-kidney share relatively similar expression patterns. We identified 814 and 181 putative target sequences for 1048 lncRNAs and 47 miRNAs, respectively. The results obtained provide new information and enlarge our understanding of the diversities of ncRNAs in coho salmon.

Novel microsatellite markers discovery in Patagonian toothfish (Dissostichus eleginoides) using high-throughput sequencing.

Patagonian toohfish (Dissostichus eleginoides), is a sub Antartic notothenioid fish key in the marine ecosystem that sustains fishery of higher commercial value in the world. However, there are a scarce knowledge or information about its population genetic background, product of the almost null information of molecular markers available for this species. Here, we use high-throughput sequencing technology (Illumina platform) to develop 1071 microsatellite loci, of which 22 loci were selected to evaluation. Polymorphism and genetic diversity of each locus was assessed in two locations distant by 2370 km. Considering both locations, a mean PIC value of 0.748 was estimated. Selected microsatellite loci showed among two to seventeen alleles by locus in the first location and two to twelve in the second. The observed heterozygosity varied from 0.18 to 0.91 and from 0.12 to 0.87 for the first and second location, respectively. While, the expected heterozygosity ranged from 0.15 to 0.92 and from 0.11 to 0.90. Three loci were monomorphic in only one location. Microsatellite markers developed here will be useful in future studies on conservation, fishery and population genetics of this species.

ATP Induces IL-1ß Secretion in Neisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis.

Neisseria gonorrhoeae (Ngo) has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses. Recent findings have reported that Ngo reduces the IL-1ß secretion of infected human monocyte-derived macrophages (MDM). Here, we investigate the role of adenosine triphosphate (ATP) in production and release of IL-1ß in Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1ß levels about ten times compared with unexposed Ngo-infected MDM (P < 0.01). However, we did not observe any changes in inflammasome transcriptional activation of speck-like protein containing a caspase recruitment domain (CARD) (ASC, P > 0.05) and caspase-1 (CASP1, P > 0.05). In addition, ATP was not able to modify caspase-1 activity in Ngo-infected MDM but was able to increase pyroptosis (P > 0.01). Notably ATP treatment defined an increase of positive staining for IL-1ß with a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1ß secretion by a mechanism not related to the NLRP3/ASC/caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation.