Changes In Plasma Proteins Research Articles

Plasma Proteomics Unveil Novel Immune Signatures and Biomarkers upon SARS-CoV-2 Infection

Several elements have an impact on COVID-19, including comorbidities, age and sex. To determine the protein profile changes in peripheral blood caused by a SARS-CoV-2 infection, a proximity extension assay was used to quantify 1387 proteins in plasma samples among 28 Finnish patients with COVID-19 with and without comorbidities and their controls. Key immune signatures, including CD4 and CD28, were changed in patients with comorbidities. Importantly, several unreported elevated proteins in patients with COVID-19, such as RBP2 and BST2, which show anti-microbial activity, along with proteins involved in extracellular matrix remodeling, including MATN2 and COL6A3, were identified. RNF41 was downregulated in patients compared to healthy controls. Our study demonstrates that SARS-CoV-2 infection causes distinct plasma protein changes in the presence of comorbidities despite the interpatient heterogeneity, and several novel potential biomarkers associated with a SARS-CoV-2 infection alone and in the presence of comorbidities were identified. Protein changes linked to the generation of SARS-CoV-2-specific antibodies, long-term effects and potential association with post-COVID-19 condition were revealed. Further study to characterize the identified plasma protein changes from larger cohorts with more diverse ethnicities of patients with COVID-19 combined with functional studies will facilitate the identification of novel diagnostic, prognostic biomarkers and potential therapeutic targets for patients with COVID-19.

Compared to preoperative plasma levels post-operative urokinase-type plasminogen activator-1 levels are persistently elevated for 6 weeks after minimally invasive colorectal resection.

Urokinase-type plasminogen activator-1 (uPA) is a serine protease that converts plasminogen to plasmin after binding to uPA receptor (uPAR). Plasmin catalyzes the regeneration of basement membrane, extracellular matrix, and other tissues. uPA alone and with plasmin leads to activation of angiogenic growth factors that impact tumor cell proliferation, adhesion, and migration. uPA over expression has been noted in colorectal cancer (CRC) and high tissue levels have been correlated with prognosis. uPA/uPAR promotes immune cell activation in healing surgical wounds and may alter perioperative uPA plasma levels. Postoperative (postop) plasma levels, if elevated, may impact the early growth of residual metastases. The impact of minimally invasive colorectal resection (MICR) surgery for CRC on plasma uPA levels is unknown. This study's aim was to measure plasma uPA levels during the first postop month. CRC patients undergoing MICR who enrolled in an Institutional Review Board (IRB) approved data/plasma bank for whom adequate plasma was available were included in the study. Patients who had chemotherapy or radiotherapy within 4 weeks, those who received blood transfusions perioperatively and immunosuppressed patients were excluded. Clinical and pathological data were prospectively collected as were blood samples preoperatively, postop day (POD) 1, 3 and at least 1 late time point between POD 7-41. Plasma was isolated and stored at -80 ℃. Late samples were bundled into 7-day blocks and considered as single time points. Total uPA levels (ng/mL) were analyzed in duplicate via enzyme-linked immunosorbent assay (ELISA) and results reported as mean ± standard deviation (SD). The Wilcoxon paired t-test was used for analysis. Ninety-three patients undergoing MICR for CRC [colonic 68%; rectal 32%; average age 65.6 years, laparoscopic 63%, hand-assisted minimally invasive surgery (MIS) 37%] who met criteria were studied. Cancer stage breakdown was; stage I, 30%, stage II, 29%, stage III, 34%, stage IV, 7%. The median preoperative (preop) uPA plasma level (ng/mL) was 529.8 [95% confidence interval (CI): 462.8, 601.1] (n=93). Significant elevations in median levels vs. preop were present during POD 3 (542.8, 95% CI: 518.8, 597.3, n=86, P=0.003), POD 7-13 (688.1, 95% CI: 591.7, 753.0, n=72, P<0.001), POD 14-20 (764.9, 95% CI: 704.1, 911.6, n=27, P<0.001), POD 21-27 (685.6, 95% CI: 443.8, 835.8, n=15, P<0.001), and on POD 28-41 (800.3, 95% CI: 626.9, 940.6, n=21, P<0.001). The colon cancer subgroup's preop and POD 14-20 median results were significantly higher than the corresponding rectal cancer results; otherwise, at the other 5 postop time points there were no significant differences between the rectal and colon cancer subgroups. In addition, no association was found between cancer stage and preop uPA levels and no significant differences were found in postop uPA levels between the hand-assisted laparoscopic group and the lap assisted subgroup at any of the postop time points. Persistently elevated plasma uPA levels at 5/6 postop time point (P<0.05), in combination with other previously demonstrated long duration proangiogenic plasma protein changes, may render the plasma proangiogenic within the period of the first month post-surgery and may promote angiogenesis within the residual tumor foci. The clinical significance pertaining to these changes, if any, is uncertain and remains to be proven.

Plasma protein profiling analysis in patients with atrial fibrillation before and after three different ablation techniques.

There are controversies on the pathophysiological alteration in patients with atrial fibrillation (AF) undergoing pulmonary vein isolation using different energy sources. We evaluated the changes in plasma proteins in acute phase post-ablation in patients receiving cryoballoon ablation, radiofrequency balloon ablation, or radiofrequency ablation. Blood samples from eight healthy controls and 24 patients with AF were taken on the day of admission, day 1, and day 2 post-ablation and analyzed by the Olink proximity extension assay. Proteins were identified and performed with enrichment analysis. Protein-protein interaction network and module analysis were conducted using Cytoscape software. Of 181 proteins, 42 proteins in the cryoballoon group, 46 proteins in the radiofrequency balloon group, and 43 proteins in the radiofrequency group significantly changed after ablation. Most of the proteins altered significantly on the first day after ablation. Altered proteins were mainly involved in cytokine-cytokine receptor interaction. Both balloon-based ablations showed a similar shift toward enhancing cell communication and regulation of signaling while inhibiting neutrophil chemotaxis. However, radiofrequency ablation presented a different trend. Seed proteins, including osteopontin, interleukin-6, interleukin-10, C-C motif ligand 8, and matrix metalloproteinase-1, were identified. More significant proteins associated with hemorrhage and coagulation were selected in balloon-based ablations by machine learning. Plasma protein response after three different ablations in patients with AF mainly occurred on the first day. Radiofrequency balloon ablation shared similar alteration in protein profile as cryoballoon ablation compared with radiofrequency ablation, suggesting that lesion size rather than energy source is the determinant in pathophysiological responses to the ablation.

Association of the changes in hepatic enzymes, bilirubin, and plasma proteins with beta-thalassemia in iron over loaded-patients

Changes in liver enzymes and bilirubin in patients with thalassemia depend on genetic changes and the association of other genetic determinants. Iron overload is associated with increased morbidity in both transfusion-dependent and non-transfusion-dependent thalassemia patients. The main objective was to evaluate hepatic enzymes, bilirubin and plasma proteins in βTM patients and also to study the correlations of these parameters with serum hemoglobin and ferritin concentrations in βTM patients. To achieve this goal, the study was directed on two groups, the first is case group includes 39 patients with βTM and the second control group includes 34 subject. Serum ALT, AST, total bilirubin, albumin and total protein concentrations were measured by UV-Vis Spectrophotometer, while the concentration of serum ferritin was measured by ELISA Kit. Our results showed that there are highly significant differences between beta thalassemia major and ferritin at mean (2942.71) , furthermore there are highly significant differences between beta thalassemia major and liver enzymes at (71.98) for AST , (69.42) for ALT, (6.98) for Total protein, (3.92) for Albumin and (2.32) for Total bilirubin. In addition our findings showed there are Correlations between serum ferritin concentrations and liver function testes in βTM patients, where there are highly significant differences between beta thalassemia major and Alanine transaminase at mean (r = 0.44), while the Correlation between serum hemoglobin concentration and liver function testes showed highly significant differences between beta thalassemia major and aspartate aminotransferase at mean (r = 0.52). The study concluded that the increase in serum liver enzymes (ALT, AST) and total bilirubin concentrations in patients with βTM are indicator to liver dysfunction that is correlated to iron overload.

Abstract 13499: Unravelling the Pathophysiology of Right Ventricular Maladaptive Hypertrophy in Chronic Pulmonary Hypertension Through Imaging and Omics

Introduction: Right ventricular (RV) failure is the strongest determinant of survival in chronic pulmonary hypertension (PH), but its pathophysiological mechanisms remain unclear. Hypothesis: In addition to RV pressure overload, compounds liberated from the pulmonary vascular damage (identifiable by omics) may exert a detrimental effect on RV function in PH. Methods: Four different experimental models of RV pressure overload in 48 Yucatan pigs were developed: chronic postcapillary PH by pulmonary veins banding (M1); chronic PH by aorto-pulmonary shunting (M2); RV pressure overload by PA banding (thus without PH) (M3); and sham procedure (M0). Animals were evaluated at 1, 5 and 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Unsupervised proteomic and metabolomic analyses were performed and compared among experimental groups and to the severity of RV dysfunction. Results: A total of 33 pigs completed follow-up (M1,n=8; M2,n=6; M3,n=10; and M0,n=9). As expected, M1&amp;M2-animals developed chronic PH, whereas M3-animals had severely increased RV systolic pressure without PH (Table). M3-pigs developed more severe RV hypertrophy (significantly higher mass on CMR and cardiomyocyte area on histology), but maintained normal function. In contrast, M1&amp;M2 animals developed RV systolic disfunction and increased myocardial apoptosis in M1. Plasma metabolomic and proteomic patterns differed among groups, highlighting greater inflammation and taurine/arginine deficiency in PH models (M1&amp;M2), coagulation disturbances in M1, and predominant lipidomic changes in M3. Key proteins/metabolites from coagulation, complement system and apolipoproteins pathways significantly associated with RV performance. Conclusion: Maladaptive RV hypertrophy in PH is associated with significant changes in plasma proteins and metabolites. Their identification may help to identify potential targets.

Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins.

Long-term changes in plasma proteomic profiles in premenopausal and postmenopausal Black and White women: the Atherosclerosis Risk in Communities study.

The activity, localization, and turnover of proteins within cells and plasma may contribute to physiologic changes during menopause and may influence disease occurrence. We examined cross-sectional differences and long-term changes in plasma proteins between premenopausal and naturally postmenopausal women. We used data from 4,508 (19% Black) women enrolled in the Atherosclerosis Risk in Communities study. SOMAscan multiplexed aptamer technology was used to measure 4,697 plasma proteins. Linear regression models were used to compare differences in proteins at baseline (1993-1995) and 18-year change in proteins from baseline to 2011-2013. At baseline, 472 women reported being premenopausal and 4,036 women reported being postmenopausal, with average ages of 52.3 and 61.4 years, respectively. A greater proportion of postmenopausal women had diabetes (15 vs 9%), used hypertension (38 vs 27%) and lipid-lowering medications (10 vs 3%), and had elevated total cholesterol and waist girth. In multivariable adjusted models, 38 proteins differed significantly between premenopausal and postmenopausal women at baseline, with 29 of the proteins also showing significantly different changes between groups over the 18-year follow-up as the premenopausal women also reached menopause. These proteins were associated with various molecular/cellular functions (cellular development, growth, proliferation and maintenance), physiological system development (skeletal and muscular system development, and cardiovascular system development and function), and diseases/disorders (hematological and metabolic diseases and developmental disorders). We observed significantly different changes between premenopausal and postmenopausal women in several plasma proteins that reflect many biological processes. These processes may help to understand disease development during the postmenopausal period.

Uncovering the functions of plasma proteins in ulcerative colitis and identifying biomarkers for BPA-induced severe ulcerative colitis: A plasma proteome analysis

Ulcerative colitis (UC), a long-term inflammation of the colon, is a worldwide disease. Accumulating reports have suggested the contribution of environmental pollutants to UC development. As such, the identification of biomarkers to evaluate pollutant-induced UC could provide a better assessment on the world’s pollution problem. In the present study, we applied the plasma proteome to profile the plasma protein changes in three models: dextran sulfate sodium (DSS)-induced colitis, bisphenol A (BPA), and BPA-severe colitis. We aimed to investigate the functional roles of plasma proteins related to colitis development and further understand the synergistic effect of BPA on colitis. In addition, we aimed to identify novel biomarkers for UC non-invasive diagnosis and assessment of BPA-induced colitis. Our results showed a significant dysregulation of plasma proteins in these three models. Bioinformatics analysis, including gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and Ingenuity Pathway Analysis, highlighted the important effects of these dysregulated plasma proteins in immune and inflammatory responses through the regulation of CCR3 signaling in eosinophils, PI3K signaling in B lymphocytes, CD28 signaling in T helper cells, and leukocyte extravasation signaling in DSS-induced colitis model. Furthermore, our data suggested that BPA exposure altered the plasma proteins involved in lipid-related metabolic processes, leukocyte cell-cell adhesion and cytokine response. More importantly, we identified plasma proteins, ALB, APOA4, C3, CFB, DPEP1, HP, LTF, and Retnlg as biomarkers for assessing BPA-induced colitis.

Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy.

Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system. Pregnancy represents a natural modulation of the disease course, where the relapse rate decreases, especially in the 3rd trimester, followed by a transient exacerbation after delivery. Although the exact mechanisms behind the pregnancy-induced modulation are yet to be deciphered, it is likely that the immune tolerance established during pregnancy is involved. In this study, we used the highly sensitive and specific proximity extension assay technology to perform protein profiling analysis of 92 inflammation-related proteins in MS patients (n=15) and healthy controls (n=10), longitudinally sampled before, during, and after pregnancy. Differential expression analysis was performed using linear models and p-values were adjusted for false discovery rate due to multiple comparisons. Our findings reveal gradual dynamic changes in plasma proteins that are most prominent during the 3rd trimester while reverting post-partum. Thus, this pattern reflects the disease activity of MS during pregnancy. Among the differentially expressed proteins in pregnancy, several proteins with known immunoregulatory properties were upregulated, such as PD-L1, LIF-R, TGF-β1, and CCL28. On the other hand, inflammatory chemokines such as CCL8, CCL13, and CXCL5, as well as members of the tumor necrosis factor family, TRANCE and TWEAK, were downregulated. Further in-depth studies will reveal if these proteins can serve as biomarkers in MS and whether they are mechanistically involved in the disease amelioration and worsening. A deeper understanding of the mechanisms involved may identify new treatment strategies mimicking the pregnancy milieu.

Effect of changes in co2, plasma protein, and hemoglobin on increasing blood acidity of patients with respiratory acidosis in the ICU room, dr. Slamet Martdirjo Pamekasan

Backgrounds: Character education is currently one of the solutions to overcome moral decline. From a psychological point of view, the character describes several potentials. Objectives: This study aims to determine the effect of P2KK on the soft skills of students at the University of Muhammadiyah Malang. Methods: The research design used was a pre-experimental group pre-posttest design. Sampling in this study used non-probability sampling with a quota sampling technique. The samples used were 100 students of the University of Muhammadiyah Malang class of 2018 who took part in P2KK batches 24 and 25. Data collection used the LEQ (Life Effectiveness Questionnaire) questionnaire with data analysis using the Wilcoxon test. Results: Soft skills of University of Muhammadiyah Malang students before participating in P2KK 72% had a medium category with an average value of 140, and soft skills after P2KK 76% had a medium category with an average value of 15. Based on the results of data analysis using the Wilcoxon test, significant results were obtained (p =0.00), meaning there are differences in soft skills before and after P2KK. Conclusion: There is an effect of P2KK on the soft skills of students at the University of Muhammadiyah Malang with an experiential learning approach that can improve soft skills. The most significant influence is on the attribute of controlling emotions. The UPT recommends it. P2KK to find out and evaluate the soft skill character of P2KK participants so that the training can specifically improve the soft skills that are lacking.

Plasma proteomic changes in response to surgical trauma and a novel transdermal analgesic treatment in dogs

Assessment of pain responses and inflammation during animal surgery is difficult because traditional methods, such as visual analogue scores, are not applicable while under anaesthesia. Acute phase proteins (APPs), such as C-reactive protein and haptoglobin, that are typically monitored in veterinary research, do not show a significant change until at least 2 h post-surgery and therefore, immediate pathophysiological changes are uncertain. The current study used sequential window acquisition of all theoretical mass spectra (SWATH-MS) to investigate plasma proteome changes that occur immediately following surgery in dogs and also to assess the efficacy of a novel transdermal ketoprofen (TK) formulation. Castration was chosen as surgical model in this study. The procedure was performed on twelve dogs (n = 6 in two groups) and blood samples were collected at 0 h, 1 and 2 h after surgery for proteomic analysis. Following surgery, there was a general downregulation of proteins, including complement C- 3, complement factor B, complement factor D, transthyretin, and proteins associated with lipid, cholesterol, and glucose metabolisms, reflecting the systemic response to surgical trauma. Many of these changes were diminished in the transdermal group (TD) since ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), inhibits prostanoids and the associated chemotactic neutrophil migration to site of tissue injury. SignificanceSWATH-MS Proteomic analysis revealed significant changes in plasma proteins, predominantly involved in early acute phase and inflammatory response at 1 & 2 h after surgery in castrated dogs. Pre-operative application of transdermal ketoprofen formulation had reduced the systemic immune response, which was confirmed by negligible alteration of proteins in transdermal treated group. A key outcome of this experiment was studying the efficacy of a novel transdermal NSAID formulation in dogs.

Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan.

The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes ( P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels ( P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.

Defining the effects of traffic-related air pollution on the human plasma proteome using an aptamer proteomic array: A dose-dependent increase in atherosclerosis-related proteins

BackgroundTraffic-related air pollution (TRAP) is a critical risk factor and major contributor to respiratory and cardiovascular disease (CVD). The effects of TRAP beyond the lungs can be related to changes in circulatory proteins. However, such TRAP-mediated changes have not been defined in an unbiased manner using a controlled human model. ObjectiveTo detail global protein changes (the proteome) in plasma following exposure to inhaled diesel exhaust (DE), a paradigm of TRAP, using controlled human exposures. MethodsIn one protocol, ex-smokers and never-smokers were exposed to filtered air (FA) and DE (300 μg PM2.5/m3), on order-randomized days, for 2 h. In a second protocol, independent never-smoking participants were exposed to lower concentrations of DE (20, 50 or 150 μg PM2.5/m3) and FA, for 4 h, on order-randomized days. Each exposure was separated by 4 weeks of washout. Plasma samples obtained 24 h post-exposure from ex-smokers (n = 6) were first probed using Slow off-rate modified aptamer proteomic array. Plasma from never-smokers (n = 11) was used for independent assessment of proteins selected from the proteomics study by immunoblotting. ResultsProteomics analyses revealed that DE significantly altered 342 proteins in plasma of ex-smokers (n = 6). The top 20 proteins therein were primarily associated with inflammation and CVD. Plasma from never-smokers (n = 11) was used for independent assessment of 6 proteins, amongst the top 10 proteins increased by DE in the proteomics study, for immunoblotting. The abundance of all six proteins (fractalkine, apolipoproteins (APOB and APOM), IL18R1, MIP-3 and MMP-12) was significantly increased by DE in plasma of these never-smokers. DE-mediated increase was shown to be concentration-dependent for fractalkine, APOB and MMP-12, all biomarkers of atherosclerosis, which correlated with plasma levels of IL-6, a subclinical marker of CVD, in independent participants. ConclusionThis investigation details changes in the human plasma proteome due to TRAP. We identify specific atherosclerosis-related proteins that increase concentration-dependently across a range of TRAP levels applicable worldwide.

Conformational changes in plasma proteins and erythrocytes in puerperal women and strategies of managing the perioperative period

BACKGROUND: Cesarean delivery is associated with prolonged hospitalization compared to spontaneous delivery and the risk of intra- and postoperative complications. The introduction of an accelerated recovery program after a planned cesarean section contributes to the rapid recovery of the patient by optimizing various elements of care.&#x0D; AIM: To study the effect of the components of the accelerated recovery program on the severity of oxidative stress during abdominal delivery at different stages of the perioperative period.&#x0D; MATERIALS AND METHODS: This was a comparative study assessing conformational changes in plasma proteins and erythrocytes in the blood of puerperal women using fluorescence spectroscopy. The study included 81 patients from the perinatal center of Makhachkala who underwent a planned cesarean section under spinal anesthesia. The enrolled women were grouped into the following: control group (n=38), in which perioperative period was traditionally managed, i.e. fasting for 8 h before the operation and introducing an antibiotic after clamping the umbilical cord. Within this group, blood sampling was conducted in all 38 patients at different intervals. In total, 152 samples of the material under study were obtained from control mothers. The 2nd group was the main (n=43) and included women in labor; in this group, perioperative period was managed using accelerated recovery program, by introducing the antibiotic cefazolin and with the intake of a glucose-containing drink 2 h before the operation. In total, 172 samples of the material under study were obtained from the mothers of the 2nd group. Methods for the pre-preparation of biological material and spectral methods of analysis were used in this study.&#x0D; RESULTS: At all stages of preparation of delivery by cesarean section (CS) after spinal anesthesia, minor conformational changes occur in the blood plasma proteins, including umbilical cord blood. In the main group, antibiotic use an hour before delivery increased the oxidative degradation of blood plasma proteins. In the control group, a change in the structural-dynamic parameters of erythrocyte membrane proteins was observed, as indicated by the blue shift in the maximum fluorescence spectrum. This was not observed in the erythrocytes of the main group of puerperal women who received a glucose-containing drink.&#x0D; CONCLUSION: According to total fluorescence data of plasma proteins and umbilical cord blood, it can be assumed that using a glucose-containing drink 2 hours before CS along with an antibiotic helps restore some parameters of the fluorescence of erythrocyte membrane proteins. The data obtained do not indicate any persistent pathological phenomena in mothers body at all stages of preparation for CS delivery using spinal anesthesia against the background of antibiotic use.

Plasma proteome of brain-dead organ donors predicts heart transplant outcome

The pathophysiological changes related to brain death may affect the quality of the transplanted organs and expose the recipients to risks. We probed systemic changes reflected in donor plasma proteome and investigated their relationship to heart transplant outcomes. Plasma samples from brain-dead multi-organ donors were analyzed by label-free protein quantification using high-definition mass spectrometry. Unsupervised and supervised statistical models were used to determine proteome differences between brain-dead donors and healthy controls. Proteome variation and the corresponding biological pathways were analyzed and correlated with transplant outcomes. Statistical models revealed that donors had a unique but heterogeneous plasma proteome with 237 of 463 proteins being changed compared to controls. Pathway analysis showed that coagulation, gluconeogenesis, and glycolysis pathways were upregulated in donors, while complement, LXR/RXR activation, and production of nitric oxide and reactive oxygen species in macrophages pathways were downregulated. In point-biserial correlation analysis, lysine-specific demethylase 3A was moderately correlated with any grade and severe PGD. In univariate and multivariate Cox regression analyses myosin Va and proteasome activator complex subunit 2 were significantly associated with the development of acute rejections with hemodynamic compromise within 30 days. Finally, we found that elevated levels of lysine-specific demethylase 3A and moesin were identified as predictors for graft-related 1-year mortality in univariate analysis. We show that brain death significantly changed plasma proteome signature Donor plasma protein changes related to endothelial cell and cardiomyocyte function, inflammation, and vascular growth and arteriogenesis could predict transplant outcome suggesting a role in donor evaluation.

Proteome Dynamics and Bioinformatics Reveal Major Alterations in the Turnover Rate of Functionally Related Cardiac and Plasma Proteins in a Dog Model of Congestive Heart Failure

Protein pool turnover is a critically important cellular homeostatic component, yet it has been little explored in the context of heart failure (HF) pathophysiology. We used in vivo 2H labeling/proteome dynamics for the nonbiased discovery of turnover alterations involving functionally linked cardiac and plasma proteins in canine tachypacing-induced HF, an established preclinical model of dilated cardiomyopathy. Compared with controls, dogs with congestive HF displayed bidirectional turnover changes of 28 cardiac proteins, that is, a reduced half-life of several key enzymes involved in glycolysis, homocysteine metabolism and glycogenesis, and increased half-life of proteins involved in proteolysis. Changes in plasma proteins were more modest: only 5 proteins, involved in various functions including proteolysis inhibition, hemoglobin, calcium and ferric iron binding, displayed increased or decreased turnover rates. In other dogs undergoing cardiac tachypacing, we infused for 2 weeks the myokine Follistatin-like protein 1, known for its ameliorative effects on HF-induced alterations. Proteome dynamics proved very sensitive in detecting the partial or complete prevention, by Follistatin-like protein 1, of cardiac and plasma protein turnover alterations. In conclusion, our study unveiled, for the first time in a large mammal, numerous HF-related alterations that may serve as the basis for future mechanistic research and/or as conceptually new molecular markers.

Effect of Therapeutic Plasma Exchange on Plasma Constituents in Neurointensive Care Unit Patients: A Retrospective Study

AbstractPurpose Plasma exchange is one of the recommended therapeutic procedures for autoimmune neurological conditions and involves removal of plasma over multiple sessions for exclusion of autoantibodies responsible for the disease process. This study aimed to evaluate the changes in the concentration of plasma constituents with five cycles of alternate day therapeutic plasma exchange (TPE), identify contributing factors for hypoproteinemia, and examine its impact on clinical outcomes.Methods This was a single-center, retrospective cohort study involving patients with autoimmune neurological diseases who underwent at least five cycles of TPE in the neurointensive care unit (NICU). Data regarding plasma protein concentrations, serum electrolytes, fluid input/output before and after every TPE cycle and clinical outcomes in terms of duration of ventilation, and NICU and hospital stay were collected from the medical records over a 1-year period.Results The levels of plasma proteins (total protein, albumin and globulin) (p &lt; 0.001), sodium (p &lt; 0.001), calcium (p &lt; 0.001), and hemoglobin (p = 0.002) declined significantly after TPE. Difference in plasma protein levels before and after TPE did not correlate with durations of mechanical ventilation and hospital and NICU stay. Difference in total protein and globulin correlated negatively with fluid balance and positively with daily protein intake (p &lt; 0.05 for both).Conclusion A significant decrease in plasma proteins and other plasma constituents is seen with TPE. Changes in plasma proteins are related to hemodilution and protein intake. Decrease in plasma proteins did not affect duration of hospital or NICU stay and duration of mechanical ventilation.

Egg incubation and plasma proteome alterations in response to brood care in maternal crayfish (Procambarus clarkii)

Little information is available on differences between maternally and artificially incubated eggs in the economically important crayfish Procambarus clarkii. Brood care in this species is expected to exert effects on the eggs. In this work, we evaluated the hatching rates of artificially incubated eggs, without brood care, compared to those maternally incubated through different development stages. We also examined whether the maternal-offspring connections in ovigerous females were related to embryonic development at the physiological level based on comparative proteomic analysis. The experiments led to two key results. First, hatching rates increased continuously throughout the nine distinct development phases when detaching maternally incubated eggs from the mothers' pleopods individually. Further, a critical period of artificially incubated eggs was observed around the gastrula stage, with the hatching rate ranging from approx. 24% to 45%. Second, blood plasma proteome profiles differed significantly between ovigerous females and aborted females during the gastrula stage (p < 0.05). Of the identified 27 differentially expressed proteins, 23 were significantly up-regulated, whereas four were down-regulated (p < 0.05). Functions of DEPs were linked to the binding, regulation, and immune response, particularly in two strongly expressed PGDH-like and CAT-like proteins (fold-change>3.0). These results suggested that the dynamic changes of plasma proteins in ovigerous females might be related to early isolated egg anti-infectivity and hence affect the hatching success. Yet, the mechanisms behind the encountered relationships need further exploration. In summary, we presented the first evidence of proteomic changes in ovigerous female plasma, revealing that brood care in P. clarkii may include more than physical behavior

Serum galectin-3BP as a novel marker of obesity and metabolic syndrome in Chinese adolescents

IntroductionChildhood obesity (OB) and metabolic syndrome (MetS) have become a worldwide health problem. Comparative proteomic approaches are widely used in human OB to analyze protein changes in blood plasma. The...

Fibrinogen Dysregulation is a Prominent Process in Fatal Conditions of COVID-19 Infection; a Proteomic Analysis.

Introduction:Molecular pathophysiology of COVID-19 is not completely known. Expression changes in patients' plasma proteins have revealed new information about the disease. Introducing the key targeted plasma protein in fatal conditions of COVID-19 infection is the aim of this study.Methods:Significant differentially expressed proteins (DEPs) in the plasma of cases with a fatal condition of COVID-19 were extracted from an original article. These proteins were included in a network via STRING database along with 100 first neighbor proteins to determine central nodes of the network for analyzing. Results:Queried and added proteins were included in a scale free network. Three hub nodes were identified as critical target proteins. The top queried hub proteins were chains of fibrinogen; Fibrinogen Alpha chain (FGA), Fibrinogen gamma chain (FGG), and Fibrinogen beta chain (FGB), which are related to the coagulation process.Conclusions:It seems that fibrinogen dysregulation has a deep impact on the fatality of COVID-19 infection.