OBJECTIVEAcute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by hypoxemic respiratory failure and diffuse alveolar inflammatory damage. This review aimed to search and discuss the mass spectrometry (MS)-based proteomic studies on different subsets of ARDS patients.

DATA SOURCESOriginal research articles were collected from the PubMed database published in English up to December 2015.

STUDY SELECTIONThe literature search was done using the term "(acute lung injury OR acute respiratory distress syndrome) AND (proteomics OR proteome OR mass spectrum OR differential in-gel electrophoresis OR two-dimensional polyacrylamide gel electrophoresis)". Related original research articles were included and were carefully analyzed.

RESULTSEight original proteomic researches on ARDS patients were found. The common proteomic modalities were two-dimensional (2D) high-performance liquid chromatography-based electronic spray ion-MS/MS and 2D-polyacrylamide gel electrophoresis/differential in-gel electrophoresis-based matrix-assisted laser desorption ionization-time of flight/MS. They compared the proteome between ARDS patients and normal controls and analyzed the dynamic changes of proteome at different ARDS stages or severity. The disturbed proteome in ARDS patients includes plasma acute-phase proteins, inflammatory/immune-associated proteins, and coagulation proteins.

CONCLUSIONSAlthough several previous studies have provided some useful information about the lung proteome in ARDS patients and gained several interesting disease-associated biomarkers, clinical proteomic studies in ARDS patients are still in the initial stage. An increased cooperation is still needed to establish a global and faithful database containing disease-specific proteome from the largest ARDS subsets.

Acute-Phase Proteins ; metabolism ; Humans ; Lung ; metabolism ; pathology ; Mass Spectrometry ; methods ; Precision Medicine ; methods ; Proteomics ; methods ; Respiratory Distress Syndrome, Adult ; metabolism

OBJECTIVE: This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. METHODS: Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. RESULTS: The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 µmol/well at the baseline to 752.5±671.9 µmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. CONCLUSION: The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.
Acute-Phase Proteins ; Adalimumab ; Alkaline Phosphatase ; Arthritis, Rheumatoid ; Biological Therapy ; Bone Remodeling ; Bone Resorption ; Etanercept ; Female ; Humans ; Infliximab ; Metabolism ; Methotrexate ; Osteoblasts* ; Osteocalcin ; Osteoclasts* ; Osteogenesis ; Tumor Necrosis Factor-alpha*

OBJECTIVETo explore beryllium oxide induced oxidative lung injury and the protective effects of LBP.

METHODSIntoxication of animals were induced by once intratracheal injection and LBP intervention by intragastric administration. The content of HIF-1, VEGF and HO-1 of lung tissues were measured by kits. The pathological changes of lung tissue were showed by pathological section. The changes of lung ultrastructure were observed by electron microscope.

RESULTSPathological changes of the lung tissue in beryllium oxide exposure group rats were in line with the characteristics of beryllium disease in human. Compared with the control group, HO-1 was increased in beryllium oxide exposure 40 d group and low doses of LBP group, compared with the control group, HO-1 was increased in beryllium oxide exposure 80d group and LBP treatment groups (P < 0.05 or P < 0.01). Compared with the control group, HIF-1 was increased in beryllium oxide exposure 40 d group, LBP treatment groups, beryllium oxide exposure 60 d and 80 d groups (P < 0.05 or P < 0.01). Compared with the control group, VEGF was increased of all phases, especially in beryllium oxide exposure 40d and 80 groups, LBP treatment groups and beryllium oxide exposure 60 d (P < 0.05 or P < 0.01). The content of HO-1 of beryllium oxide exposure group was higher than the LBP treatment for 40d group but below LBP treatment for 80 d group (P < 0.05). The content of HIF1 of beryllium oxide exposure group was higher than high dose of LBP treatment for 60d group and LBP treatment for 80 d group (P < 0.01). The content of VEGF of beryllium oxide exposure group was higher than LBP treatment for 40 d group and high dose of LBP treatment for 60 d (P < 0.05 or P < 0.01).

CONCLUSIONSBeO can cause abnormal expression of related genes of lung tissue in rats, LBP has protective effects on BeO caused lung injury.

Acute Lung Injury ; chemically induced ; physiopathology ; Acute-Phase Proteins ; pharmacology ; Animals ; Beryllium ; toxicity ; Carrier Proteins ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Lung ; drug effects ; pathology ; Membrane Glycoproteins ; pharmacology ; Oxidative Stress ; Protective Agents ; pharmacology ; Rats ; Vascular Endothelial Growth Factor A ; metabolism

No abstract available.
Acute-Phase Proteins/*urine ; Female ; Glomerulonephritis, IGA/*blood/*urine ; Humans ; Kidney/*metabolism ; Lipocalins/*blood/*urine ; Male ; Proto-Oncogene Proteins/*blood/*urine

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.
Acute-Phase Proteins/*urine ; Adult ; Biomarkers/blood/urine ; Biopsy ; Chi-Square Distribution ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology/*urine ; Humans ; Kaplan-Meier Estimate ; Kidney/*metabolism/pathology/physiopathology ; Lipocalins/*blood/*urine ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood/*urine ; Retrospective Studies ; Risk Factors ; Young Adult

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. RESULTS: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.
Acute-Phase Proteins ; Adolescent ; Adult ; Aged ; Biomarkers/blood ; Biopsy ; Chi-Square Distribution ; Creatinine/blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology ; Humans ; Kidney/*metabolism/pathology/physiopathology ; Linear Models ; Lipocalins/*blood ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood ; Renal Insufficiency, Chronic/blood/etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Young Adult

Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family. As a novel adipokine, it widely presents in the tissues under the condition of metabolic disorders. More and more studies suggest that NGAL might be a marker for a variety of diseases associated with lipid metabolism. It is likely that NGAL plays an important role in obese-inflammation-induced metabolic syndrome,insulin resistance, glucose and lipid metabolism, endothelial dysfunction and atherosclerosis pathway.
Acute-Phase Proteins ; metabolism ; Atherosclerosis ; Biomarkers ; metabolism ; Humans ; Inflammation ; Insulin Resistance ; Lipocalin-2 ; Lipocalins ; metabolism ; Metabolic Syndrome ; metabolism ; physiopathology ; Obesity ; Proto-Oncogene Proteins ; metabolism

OBJECTIVETo explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury (ALI) in mice.

METHODSLipopolysaccharide (LPS, 10 mg/kg) injection or cecal ligation and puncture (CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups (n=10 in each group): group A (intraperitoneal LPS injection), group B (intravenous LPS injection via tail vein), group C (CLP with 25% of the cecum ligated), group D (CLP with 75% of the cecum ligated), and the control group (6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin (IL)-6 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves (ROC) and computing area under curve (AUC).

RESULTSIn both group B and group D, most of the main features of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI (group A+group C), lipocalin-2 protein expression in septic mice with ALI (group B+group D) was significantly up-regulated in BALF (P<0.01) and in serum (P<0.01), and mRNA expression boosted in lung tissues (all P<0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former (BALF tests, 0.8800 versus 0.6625; serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio (13.000) and the lowest negative likelihood ratio (0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum (Spearman r=0.8803, P<0.0001).

CONCLUSIONSLipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.

Acute-Phase Proteins ; metabolism ; Animals ; Base Sequence ; Bronchoalveolar Lavage Fluid ; DNA Primers ; Lipocalin-2 ; Lipocalins ; metabolism ; Lung Injury ; complications ; diagnosis ; Male ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins ; metabolism ; Real-Time Polymerase Chain Reaction ; Sepsis ; complications

PURPOSE: To evaluate plasma pentraxin 3 (PTX3) in patients with retinal vein occlusion (RVO), and investigate the possibility of its role as a predictive biomarker. METHODS: Nested case-control study. The study included 57 patients with RVO and 45 age- and gender-matched subjects without RVO as controls. Plasma PTX3 and C-reactive protein concentration were measured in both groups a posteriori from frozen samples by using an enzyme-linked immunosorbent assay kit. RESULTS: The measured PTX3 value for the RVO group was 1,508 +/- 1,183 pg/mL (mean +/- standard deviation) and 833 +/- 422 pg/mL for the controls (p < 0.001). There was no significant difference in PTX3 levels between patients with central retinal vein occlusion and branched retinal vein occlusion (1,468 +/- 1,300 vs. 1,533 +/- 1,121 pg/mL; p = 0.818). CONCLUSIONS: Our data seems to support the role of chronic inflammation and ischemia in the development of RVO. It is possible that PTX3 can be used as a diagnostic biomarker of RVO.
Acute-Phase Proteins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers/*blood ; C-Reactive Protein/*metabolism ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Retinal Vein Occlusion/*blood/diagnosis ; Serum Amyloid P-Component/*metabolism

OBJECTIVE: To determine the pathological mechanism and prevent heart-renal syndrome after heart valve replacement surgery. METHODS: A total of 46 patients were admitted for selective valve replacement, and divide into 3 groups randomly: a control group (Con, n=16), a remote ischemic perconditioning (RIPerC) group (n=15) and a remote ischemic postconditioning (RIPostC) group (n=15). The serum creatinine (SCr), blood urea nitrogen (BUN), serum heme oxygennase-1 (HO-1), serum iron and urinary neutrophil gelatinase associated lipocalin (NGAL) level in the 3 groups were compared preoperatively and 6, 12, 24, 48 h after aortic cross-release. RESULTS: Compared with the preoperative level, the SCr, BUN, urinary NGAL, serum iron (6 and 12 h) and serum HO-1 values were significantly increased after the heart valve replacement surgery in the control patients, RIPreC and RIPostC groups (P<0.05). Compared with the control group, the serum HO-1 was significantly increased at 6, 12, 24, 48 h after the heart valve replacement surgery in both the RIPerC and RIPostC groups (P<0.05); the SCr, BUN, urinary NGAL and serum iron values were decreased at 6, 12, 24, 48 h after the heart valve replacement surgery in both the RIPerC and RIPostC groups (P>0.05). CONCLUSION Abnormal change in urinary NGAL, serum iron and HO-1 can be used as early warning indicators of acute kidney injury when cardio-renal syndrome occurrs among patients under heart valve replacement surgery. Remote ischemic conditioning plays a preventive role in the occurrence of cardio-renal syndrome and renal protection.
Acute Kidney Injury ; metabolism ; Acute-Phase Proteins ; metabolism ; Blood Urea Nitrogen ; Cardiac Surgical Procedures ; adverse effects ; Creatinine ; blood ; Heme Oxygenase-1 ; metabolism ; Humans ; Iron ; blood ; Ischemic Postconditioning ; Ischemic Preconditioning ; Lipocalin-2 ; Lipocalins ; metabolism ; Proto-Oncogene Proteins ; metabolism