Additional file 1 of Alterations in trimethylamine-N-oxide in response to Empagliflozin therapy: a secondary analysis of the EMMY trial

Additional file 1: Fig. S1. Distribution of untransformed TMAO concentration (μmol/L) by treatment groups at A—baseline, B—6 weeks, and C—26 weeks. Table S1. LDL-C levels over visits by treatment groups

Branched-Chain Amino Acids as New Biomarkers of Major Depression - A Novel Neurobiology of Mood Disorder

<div><p>Background</p><p>The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are altered in patients with major depression and might thus be appropriate biomarkers for major depression.</p><p>Methods</p><p>The concentrations of valine, leucine and isoleucine were determined in 71 in-patients with major depression and 48 healthy controls by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at the time of in-patient admittance.</p><p>Results</p><p>The BCAAs are significantly decreased in patients with major depression in comparison with healthy subjects (valine: Mann-Whitney-U: 968.0; p <0.0001, leucine: Mann-Whitney-U: 1246.5; p = 0.013, isoleucine: Mann-Whitney-U: 1252.5; p = 0.014). Furthermore, as shown by Spearman's rank correlation coefficients, there is a significant negative correlation between valine, leucine and isoleucine concentrations and the Hamilton Depression Rating Scale (HAMD-17) as well as Beck Depression Inventory (BDI-II) scores.</p><p>Conclusions</p><p>Our study results are strong evidence that in patients with major depression, BCAAs might be appropriate biomarkers for depression. Reduced activation of the mammalian target of rapamycin (mTor) due to a reduction of BCAAs might play a crucial unrecognised factor in the etiology of depression and may evoke depressive symptomatology and lower energy metabolism in patients with major depression. In the future, mTor and its up- and downstream signalling partners might be important targets for the development of novel antidepressants.</p></div

Spearman's rank correlation coefficients between branched-chain amino acids and Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI-II) scores.

<p>Spearman's rank correlation coefficients between branched-chain amino acids and Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI-II) scores.</p

Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults

<div><p>Background</p><p>Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (n_juvenile = 266, n_adults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians.</p><p>Methodology and Principal Findings</p><p>Using SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2–2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects.</p><p>Conclusions and Significance</p><p>By investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor.</p></div

Biological assessments for the patients with major depression at the time of in-patient admittance to the Department of Psychiatry and healthy controls.

<p>Biological assessments for the patients with major depression at the time of in-patient admittance to the Department of Psychiatry and healthy controls.</p

HAMD-17 and BDI-II scores for the patients with major depression and healthy controls [14].

<p>HAMD-17 and BDI-II scores for the patients with major depression and healthy controls [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160542#pone.0160542.ref014" target="_blank">14</a>].</p

Interleukin-10: An Anti-Inflammatory Marker To Target Atherosclerotic Lesions via PEGylated Liposomes

Atherosclerosis (AS) causes cardiovascular disease, which leads to fatal clinical end points like myocardial infarction or stroke, the most prevalent causes of death in developed countries. An early, noninvasive method of detection and diagnosis of atherosclerotic lesions is necessary to prevent and treat these clinical end points. Working toward this goal, we examined recombinant interleukin-10 (IL-10), stealth liposomes with nanocargo potency for NMRI relevant contrast agents, and IL-10 coupled to stealth liposomes in an ApoE-deficient mouse model using confocal laser-scanning microscopy (CLSM). Through <i>ex vivo</i> incubation and imaging with CLSM, we showed that fluorescently labeled IL-10 is internalized by AS plaques, and a low signal is detected in both the less injured aortic surfaces and the arteries of wild-type mice. <i>In vivo</i> experiments included intravenous injections of (i) fluorescent IL-10, (ii) IL-10 targeted carboxyfluorescin (CF−) labeled stealth liposomes, and (iii) untargeted CF-labeled stealth liposomes. Twenty-four hours after injection the arteries were dissected and imaged <i>ex vivo</i>. Compared to free IL-10, we observed a markedly stronger fluorescence intensity with IL-10 targeted liposomes at AS plaque regions. Moreover, untargeted CF-labeled liposomes showed only weak, unspecific binding. Neither free IL-10 nor IL-10 targeted liposomes showed significant immune reaction when injected into wild-type mice. Thus, the combined use of specific anti-inflammatory proteins, high payloads of contrast agents, and liposome particles should enable current imaging techniques to better recognize and visualize AS plaques for research and prospective therapeutic strategies

Sociodemographic and clinical characteristics of the participants [14].

<p>Sociodemographic and clinical characteristics of the participants [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160542#pone.0160542.ref014" target="_blank">14</a>].</p

Frequencies (%) of CR polymorphisms higher than 5% in either overweight and obese or normal weight adults (both SAPHIR cohort) and odds ratios (OR) for the association between genetic variation and disease state.

<p>¹n: number of individuals with the respective polymorphism.</p><p>2 p-value: derived from Mann-Whitney-U test.</p><p>3 OR: Odds Ratio</p><p>4 CI: Confidence Interval</p><p>5 adjusted for sex and age</p><p>Frequencies (%) of CR polymorphisms higher than 5% in either overweight and obese or normal weight adults (both SAPHIR cohort) and odds ratios (OR) for the association between genetic variation and disease state.</p

Frequencies (%) of Caucasian mitochondrial haplogroups in juvenile obesity cases and controls.

<p>n¹ = Number of individuals with respective mtDNA haplogroup.</p><p>2Haplogroups that could not be assigned to one of the nine major European haplogroups by the SNP combination.</p><p>3Juvenile obese cohort 1</p><p>⁴Juvenile control cohort</p><p>Frequencies (%) of Caucasian mitochondrial haplogroups in juvenile obesity cases and controls.</p