Sex-specific correlation of IGFBP-2 and IGFBP-3 with vitamin D status in adults with obesity: a cross-sectional serum proteomics study

Objective: Subjects with low vitamin D levels are at risk of cardiometabolic disease. The aim of this study was to identify novel serological markers linking vitamin D status with cardiometabolic profile in non-diabetic adults with obesity. Methods: For the discovery phase, we used quantitative serum proteomics in sex-matched, age-matched and BMI-matched subjects with obesity [BMI: 25–35 kg/m^2] and low [25(OH)D  50 nmol/L] (n = 16). For the validation phase, we performed ELISA in a larger cohort with similar characteristics (n = 179). Results: We identified 423 and 549 differentially expressed proteins in the high vs. low vitamin D groups of the male and female cohorts, respectively. The small molecule biochemistry protein networks and the glycolysis|gluconeogenesis pathway were significantly enriched in the DEPs of both sexes. As surrogate markers to these processes, the insulin-like growth factor binding protein -2 (IGFBP-2) was upregulated in males, whereas IGFBP-3 was upregulated in females from the high Vitamin D status. This sex-specific trend was confirmed using Luminex ELISA to an independent but clinically analogous cohort of males (n = 84, p = 0.002) and females (n = 95, p = 0.03). Conclusions: The high Vitamin D status correlated with the serological upregulation of IGFBP-2 in males and IGFBP-3 in females with obesity and may constitute surrogate markers of risk reduction of cardiometabolic disease

Integrated eutopic endometrium and non-depleted serum quantitative proteomic analysis identifies candidate serological markers of endometriosis

Background: Endometriosis affects about 4% of women in the reproductive age and is associated with subfertility. The aim of the present study was to examine the quantitative proteomic profile of eutopic endometrium and serum from women with endometriosis compared to controls in order to identify candidate disease-specific serological markers.Methods: Eutopic endometrium and serum from patients with endometriosis (n=8 for tissue and n=4 for serum) was respectively compared to endometrium and serum from females without endometriosis (n=8 for tissue and n=4 for serum) using a shotgun quantitative proteomics method. All study participants were at the proliferative phase of their menstrual cycle.Results: At the tissue and serum level, 1,214 and 404 proteins were differentially expressed (DEPs) in eutopic endometrium and serum respectively of women with endometriosis vs. control. Gene ontology analysis showed that terms related to immune response | inflammation, cell adhesion | migration and blood coagulation were significantly enriched in the DEPs of eutopic endometrium as well as serum. Twenty-one DEPs had the same trend of differential expression in both matrices and can be further examined as potential disease- and tissue-specific serological markers of endometriosis.Conclusions: The present in-depth proteomic profiling of eutopic endometrium and serum from women with endometriosis identified promising serological markers that can be further validated in larger cohorts for the minimally invasive diagnosis of endometriosis.<br/

Integrated Eutopic Endometrium and Non-Depleted Serum Quantitative Proteomic Analysis Identifies Candidate Serological Markers of Endometriosis

Background: Endometriosis affects about 4% of women in the reproductive age and is associated with subfertility. The aim of the present study is to examine the integrated quantitative proteomic profile of eutopic endometrium and serum from women with endometriosis compared to controls in order to identify candidate disease‐specific serological markers. Methods: Eutopic endometrium and serum from patients with endometriosis (n = 8 for tissue and n = 4 for serum) are, respectively, compared to endometrium and serum from females without endometriosis (n = 8 for tissue and n = 4 for serum) using a shotgun quantitative proteomics method. All study participants are at the proliferative phase of their menstrual cycle. Results: At the tissue and serum level, 1214 and 404 proteins are differentially expressed (DEPs) in eutopic endometrium and serum, respectively, of women with endometriosis versus controls. Gene ontology analysis shows that terms related to immune response/inflammation, cell adhesion/migration, and blood coagulation are significantly enriched in the DEPs of eutopic endometrium, as well as serum. Twenty‐one DEPs have the same trend of differential expression in both matrices and can be further examined as potential disease‐ and tissue‐specific serological markers of endometriosis. Conclusions: The present integrated proteomic profiling of eutopic endometrium and serum from women with endometriosis identify promising serological markers that can be further validated in larger cohorts for the minimally invasive diagnosis of endometriosis

Integrated Eutopic Endometrium and Non-Depleted Serum Quantitative Proteomic Analysis Identifies Candidate Serological Markers of Endometriosis

Background: Endometriosis affects about 4% of women in the reproductive age and is associated with subfertility. The aim of the present study is to examine the integrated quantitative proteomic profile of eutopic endometrium and serum from women with endometriosis compared to controls in order to identify candidate disease‐specific serological markers. Methods: Eutopic endometrium and serum from patients with endometriosis (n = 8 for tissue and n = 4 for serum) are, respectively, compared to endometrium and serum from females without endometriosis (n = 8 for tissue and n = 4 for serum) using a shotgun quantitative proteomics method. All study participants are at the proliferative phase of their menstrual cycle. Results: At the tissue and serum level, 1214 and 404 proteins are differentially expressed (DEPs) in eutopic endometrium and serum, respectively, of women with endometriosis versus controls. Gene ontology analysis shows that terms related to immune response/inflammation, cell adhesion/migration, and blood coagulation are significantly enriched in the DEPs of eutopic endometrium, as well as serum. Twenty‐one DEPs have the same trend of differential expression in both matrices and can be further examined as potential disease‐ and tissue‐specific serological markers of endometriosis. Conclusions: The present integrated proteomic profiling of eutopic endometrium and serum from women with endometriosis identify promising serological markers that can be further validated in larger cohorts for the minimally invasive diagnosis of endometriosis

Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: plasma proteomics in the randomized WELCOME* trial

Summary Background &amp; aims Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterised by liver fat accumulation and often considered to be the liver manifestation of metabolic syndrome. The aim of this study was to examine in patients with NAFLD the system-wide effects of treatment with docosahexaenoic acid + eicosapentaenoic acid (DHA + EPA) versus placebo on the plasma proteome. Methods Plasma from patients that participated in a 15�18 months randomised, double-blind placebo-controlled trial testing the effects of 4 g DHA + EPA daily was analysed using depletion-free quantitative proteomics. Results Bioinformatics interpretation of the proteomic analysis showed that DHA + EPA treatment affected pathways involving blood coagulation, immune/inflammatory response and cholesterol metabolism (p &lt; 0.05). Two key proteins of cardiovascular risk, prothrombin and apolipoprotein B-100, were shown to decrease as a result of DHA + EPA supplementation [Prothrombin: Males DHA + EPA Mean iTRAQ log2ratio (SD) = �0.13 (0.20) p = 0.05, Females DHA + EPA Mean iTRAQ log2ratio (SD) = �0.48 (0.35) p = 0.03; Apo B-100: Males DHA + EPA Mean iTRAQ log2ratio (SD) = �0.24 (0.16) p = 0.01, Females DHA + EPA Mean iTRAQ log2ratio (SD) = �0.15 (0.05) p = 0.02]. Conclusions Plasma proteomics applied in a randomised, placebo-controlled trial showed that high dose DHA + EPA treatment in patients with NAFLD affects multiple pathways involved in chronic non-communicable diseases

Nitrosative responses in citrus plants exposed to six abiotic stress conditions

Nitrosative status has emerged as a key component in plant response to abiotic stress; however, knowledge on its regulation by different environmental conditions remains unclear. The current study focused on nitrosative responses in citrus plants exposed to various abiotic stresses, including continuous light, continuous dark, heat, cold, drought and salinity. Morphological observations and physiological analysis showed that abiotic stress treatments were sensed by citrus plants. Furthermore, it was revealed that nitrosative networks are activated by environmental stress factors in citrus leaves as evidenced by increased nitrite (NO) content along with the release of NO and superoxide anion (O2radical dot−) in the vascular tissues. The expression of genes potentially involved in NO production, such as NR, AOX, NADHox, NADHde, PAO and DAO, was affected by the abiotic stress treatments demonstrating that NO-derived nitrosative responses could be regulated by various pathways. In addition, S-nitrosoglutathione reductase (GSNOR) and nitrate reductase (NR) gene expression and enzymatic activity displayed significant changes in response to adverse environmental conditions, particularly cold stress. Peroxynitrite (ONOO−) scavenging ability of citrus plants was elicited by continuous light, dark or drought but was suppressed by salinity. In contrast, nitration levels were elevated by salinity and suppressed by continuous light or dark. Finally, S-nitrosylation patterns were enhanced by heat, cold or drought but were suppressed by dark or salinity. These results suggest that the nitrosative response of citrus plants is differentially regulated depending on the stress type and underscore the importance of nitrosative status in plant stress physiology