OBJECTIVETo investigate the changes of plasma gelsolin level in patients with critical illness and its application in prognostic evaluation.

METHODSNinety six critically ill patients admitted in ICU of Sichuan Provincial People's Hospital from February 2012 to December 2013 were enrolled in the prospective cohort study. Plasma gelsolin levels were detected with enzyme linked immunosorbent assay (ELISA) at admission (d1), d2, d4 and d8 after admission, and also detected in blood samples of 186 healthy subjects as controls. Logistic regression model was used to analyze the relationship between the level of plasma gelsolin and prognosis of patients.

RESULTSThe average levels of plasma gelsolin were significantly lower in critically ill patients than those in control subjects (F=1986.37, P<0.01). There was significant difference in overall level of gelsolin between survival patients and fatal patients (F=16.691, P<0.01). APACHE Ⅱ score was associated with survival outcomes (r=0.489, P=0.009); the APACHE Ⅱ score was significantly higher in fatal patients than that in survival patients (29.5±7.7 vs 22.1±5.7, t=5.375, P<0.01). There was a negative correlation between plasma gelsolin levels and fatal outcomes (r=-0.512, P<0.01). Logistic regression analysis showed that the overall plasma gelsolin levels and the last measured level was a prognostic factor for critically ill patients (P<0.05).

CONCLUSIONPlasma gelsolin levels are correlated with the severity of critically ill patients, and plasma gelsolin can be used as indicator of prognosis.

APACHE ; Case-Control Studies ; Critical Illness ; Enzyme-Linked Immunosorbent Assay ; Gelsolin ; blood ; Humans ; Logistic Models ; Plasma ; Prognosis ; Prospective Studies

OBJECTIVETo observe the changes in plasma gelsolin (pGSN) level of patients with severe burn and to explore its relationship with sepsis and death of patients.

METHODSOne hundred and two patients with total burn area equal to or larger than 30% TBSA hospitalized from May 2010 to May 2012 were included as burn group. Twenty-five healthy volunteers were recruited as healthy control group. Peripheral venous blood of patients was harvested on post burn day (PBD) 1, 3, 7, 14, and 21 to determine the pGSN level with double antibody sandwich ELISA kits, and the same maneuver was carried out in healthy volunteers. (1) Patients in burn group were divided into three groups by burn size: small burn area group (30% - 49% TBSA, n = 39), medium burn area group (larger than 49% and smaller than or equal to 69% TBSA, n = 33), and large burn area group (larger than 69% and smaller than or equal to 99% TBSA, n = 30). (2) According to diagnostic criteria of burn sepsis, patients in burn group were divided into sepsis group (n = 43) and non-sepsis group (n = 59). (3) According to the prognosis of patients with sepsis, patients in sepsis group were further divided into non-survival sepsis group (n = 14) and survival sepsis group (n = 29). The levels of pGSN in above groups were compared, and their relationship with sepsis and death of patients was analyzed. Data were analyzed with analysis of variance, LSD test and one-way Logistic regressions.

RESULTS(1) Levels of pGSN in burn group were obviously lower than those of healthy control group on PBD 1, 3, 7, 14, and 21 (with F values respectively 140.01, 369.52, 702.15, 360.14, 84.16, P values all below 0.01). (2) The mean levels of pGSN in large, medium, and small burn area groups at five time points were (43 ± 11), (85 ± 23), (124 ± 38) mg/L, showing statistically significant differences among them (F = 367.76, P < 0.01), and they were all lower than that of healthy control group [(326 ± 51) mg/L, P values all below 0.01]. (3) The mean levels of pGSN in sepsis group and non-sepsis group at the five time points were (77 ± 12), (122 ± 38) mg/L. Levels of pGSN in sepsis group were lower than those in non-sepsis group on PBD 3, 7, 14, and 21 (with F values respectively 30.35, 111.59, 209.36, 422.76, P values all below 0.01). (4) The mean levels of pGSN in non-survival sepsis group and survival sepsis group at the five time points were (53 ± 8) and (103 ± 25) mg/L. Levels of pGSN in non-survival sepsis group were lower than those in survival sepsis group on PBD 1, 3, 7, 14, and 21 (with F values respectively 9.05, 18.48, 41.34, 107.11, 180.48, P values all below 0.01). (5) Logistic regression analysis showed that the level of pGSN is the independent risk factor related to the complication of sepsis (odds ratio: 5.44, 95% confidence interval: 2.35 - 12.74, P < 0.01) and death (odds ratio: 5.52, 95% confidence interval: 2.34 - 12.19, P < 0.01) in burn patients.

CONCLUSIONSSevere burn injury could down-regulate the pGSN level of patients, and it decreases along with the increase in the area and severity of burn trauma. pGSN level appears to be an early prognostic marker for patients suffering from severe burns.

Adolescent ; Adult ; Burns ; blood ; complications ; Case-Control Studies ; Female ; Gelsolin ; blood ; Humans ; Male ; Middle Aged ; Prognosis ; Sepsis ; etiology ; Young Adult

PURPOSE: To report the first case of lattice corneal dystrophy, gelsolin type in Korea. CASE SUMMARY: A 61-year-old man visited our clinic with severe dry eye symptom in both eyes. Clinical examination revealed in both eyes a visual acuity of 0.7 without correction and intraocular pressure of 18 mm Hg. On slit-lamp examination, both corneas had scattered lattice lines at various depths within the stroma with punctate epithelial erosions. The patient had characteristic features of Meretoja syndrome, including cranial neuropathy characterized by dermatochalasis and facial weakness, and was positive for the gelsolin mutation according to DNA analysis. This is the first description of a patient with lattice corneal dystrophy, gelsolin type in Korea. CONCLUSIONS: This is the first description of a patient with lattice corneal dystrophy, gelsolin type in Korea and demonstrates the importance of recognizing the systemic and ophthalmic features for appropriate management of the condition.
Amyloidosis ; Cornea ; Corneal Dystrophies, Hereditary ; Cranial Nerve Diseases ; DNA ; Eye ; Gelsolin ; Humans ; Intraocular Pressure ; Korea ; Visual Acuity

BACKGROUND: Gelsolin and matrix metalloproteinase 12 (MMP12) expression has been reported in Langerhans cell histiocytosis (LCH), but the clinical significance of this expression is unknown. We investigated the associations of these proteins with clinical manifestations in patients diagnosed with LCH. METHODS: We performed a retrospective analysis of clinical data from patients diagnosed with LCH and followed up between 1998 and 2008. Available formalin-fixed, paraffin-embedded specimens were used for gelsolin and MMP12 immunohistochemical staining. We analyzed the expression levels of these proteins and their associations with LCH clinical features. RESULTS: Specimens from 36 patients (20 males, 16 females) with a diagnosis of LCH based on CD1a positivity with clinical manifestations were available for immunohistochemical staining. Median patient age was 62 months (range, 5 to 207). The expression of gelsolin varied; it was high in 17 patients (47.2%), low in 11 patients (30.6%), and absent in 8 patients (22.2%). The high gelsolin expression group had a higher tendency for multi-organ and risk organ involvement, although the trend was not statistically significant. MMP12 was detected only in 7 patients (19.4%) who showed multi-system involvement (P=0.018) and lower event-free survival (P=0.002) in comparison to patients with negative MMP12 staining. CONCLUSION: Gelsolin and MMP12 expression may be associated with the clinical course of LCH, and MMP12 expression may be particularly associated with severe LCH. Further studies of larger populations are needed to define the precise role and significance of gelsolin and MMP12 in the pathogenesis of LCH.
Disease-Free Survival ; Gelsolin ; Histiocytosis ; Histiocytosis, Langerhans-Cell ; Humans ; Immunohistochemistry ; Langerhans Cells ; Male ; Matrix Metalloproteinase 12 ; Proteins ; Retrospective Studies

Hereditary gelsolin amyloidosis (HGA) is an autosomal dominant hereditary disease characterized by corneal lattice dystrophy, peripheral neuropathy, and cutis laxa. So far, no Korean patients with HGA have been reported. A 58-yr-old man presented with involuntary facial twitching, progressive bilateral facial weakness, and tongue atrophy. His mother, maternal uncle, two sisters, and son suffered from the same symptoms. Electrophysiological studies revealed signs of chronic denervation in the cervical and lumbar regions, mild sympathetic autonomic dysfunction, and bilateral facial nerve dysfunction. Diagnostic whole-exome sequencing (WES) revealed a p.D214Y heterozygous mutation in the gelsolin gene in affected members. We present the first report of a Korean family with HGA diagnosed by WES. WES facilitated a clinical diagnosis of HGA in patients with undiagnosed neuropathies.
Amyloidosis, Familial/diagnosis/*genetics ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; DNA Mutational Analysis ; Gelsolin/*genetics ; Genotype ; Heterozygote ; Humans ; Male ; Middle Aged ; Pedigree ; Polymorphism, Single Nucleotide ; Republic of Korea

PURPOSE: The pathophysiological mechanisms of the bladder dysfunction in postmenopausal state are not well understood especially in moleclular level. Therefore we investigated the changes of bladder in female rat following bilateral ovariectomy by proteomic approach. MATERIALS AND METHODS: A total 10 female Sprague-Dawley rats were obtained at 8 weeks of age and randomly divided into 2 groups in each 5 rats; sham operation group as the control group and the bilateral ovariectomy group. Whole urinary bladders of the rats were excised 4 weeks after the beginning of the experiment. Conventional proteomics was performed with high resolution 2-D gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry. RESULTS: Bladder weight was not changed by oophorectomy. A comparison of bladder of ovariectomy group with control showed that 8 proteins; Eukaryotic translation initiation factor 5A was over-expressed, and chaperone grp 75 precursor, guanine deaminase, keratin complex 2, Gelsolin precursor, peroxiredoxin 2, Enol protein and contrapsin-like inhibitor 1 precursor were under-expressed in the oophorectomy group. CONCLUSION: These data suggested that the bilateral oophorectomy might make a bladder to have a cellular apoptosis and a change of contractility in the rat bladder. However more information is needed in human bladder tissue for clinical usage and long-term proteomic changes are needed.
Animals ; Apoptosis ; Electrophoresis, Gel, Two-Dimensional ; Female ; Female* ; Gelsolin ; Guanine Deaminase ; Humans ; Mass Spectrometry ; Ovariectomy* ; Peptide Initiation Factors ; Peroxiredoxins ; Proteomics ; Rats* ; Rats, Sprague-Dawley ; Urinary Bladder*

OBJECTIVE: To investigate the clinical significance of SCIN gene expression and promoter methylation in patients with chronic myeloid leukemia (CML). METHODS: Real-time quantitative PCR was used to detect the expression level of SCIN in mononucleatr cells of bone marrow samples from 64 CML patients and 37 controls. The methylation levels of SCIN promoter in 65 patients with CML and 29 controls were detected by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR. RESULTS: The expression level of SCIN in CML patients was significantly down-regulated (P＜0.05), compared with the control group. The down-regulation rate of SCIN expression in CML patients at chronic phase, accelerated phase and blast crisis was 61%, 67% and 75%, respectively. Spearman correlation analysis showed that the expression level of SCIN negatively correlated with the transcript level of BCR-ABL1 (R=-0.315, P＜0.05). However, there was no significant difference in clinical parameters such as sex, age, white blood cell count, hemoglobin level, platelet count, chromosome, CML staging and BCL-ABL1 transcript level between low and high SCIN expression groups of CML patients (P＞0.05). No significant difference in methylation of SCIN promoter between CML patients and controls, and no correlation between SCIN expression and promoter methylation were observed (P＞0.05). CONCLUSION The SCIN expression is down-regulated in CML patients, which may relate with the pathogenesis that is, BCR-ABL1 fusion gene induces CML tumorigenesis. The down-regulation of SCIN expression may relate with the progression of CML.
Blast Crisis ; DNA Methylation ; Down-Regulation ; Fusion Proteins, bcr-abl ; Gelsolin ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Promoter Regions, Genetic

This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer's disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain site-specific proteomic strategy, we identified 950 proteins in the Hp, pCx and Cb of AD brains. Of these proteins, 31 were significantly altered. Most of the differentially regulated proteins are involved in molecular transport, nervous system development, synaptic plasticity and apoptosis. Particularly, proteins such as Gelsolin (GSN), Tenascin-R (TNR) and AHNAK could potentially act as novel biomarkers of aging-related neurodegeneration. Importantly, our Ingenuity Pathway Analysis (IPA)-based network analysis further revealed ubiquitin C (UBC) as a pivotal protein to interact with diverse AD-associated pathophysiological molecular factors and suggests the reduced ubiquitin proteasome degradation system (UPS) as one of the causative factors of AD.
Aged, 80 and over ; Alzheimer Disease/*metabolism ; Brain/*metabolism ; Female ; Gelsolin/genetics/metabolism ; Humans ; Male ; Membrane Proteins/genetics/metabolism ; Neoplasm Proteins/genetics/metabolism ; Organ Specificity ; Proteome/genetics/*metabolism ; Tenascin/genetics/metabolism ; Ubiquitin C/genetics/metabolism

PURPOSE: Pleural effusion, an accumulation of fluid in the pleural space, usually occurs in patients when the rate of fluid formation exceeds the rate of fluid removal. The differential diagnosis of tuberculous pleurisy and malignant pleural effusion is a difficult task in high tuberculous prevalence areas. The aim of the present study was to identify novel biomarkers for the diagnosis of pleural fluid using proteomics technology. MATERIALS AND METHODS: We used samples from five patients with transudative pleural effusions for internal standard, five patients with tuberculous pleurisy, and the same numbers of patients having malignant effusions were enrolled in the study. We analyzed the proteins in pleural fluid from patients using a technique that combined two-dimensional liquid-phase electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. RESULTS: We identified a total of 10 proteins with statistical significance. Among 10 proteins, trasthyretin, haptoglobin, metastasis-associated protein 1, t-complex protein 1, and fibroblast growth factor-binding protein 1 were related with malignant pleural effusions and human ceruloplasmin, lysozyme precursor, gelsolin, clusterin C complement lysis inhibitor, and peroxirexdoxin 3 were expressed several times or more in tuberculous pleural effusions. CONCLUSION: Highly expressed proteins in malignant pleural effusion were associated with carcinogenesis and cell growth, and proteins associated with tuberculous pleural effusion played a role in the response to inflammation and fibrosis. These findings will aid in the development of novel diagnostic tools for tuberculous pleurisy and malignant pleural effusion of lung cancer.
Biomarkers* ; Carcinogenesis ; Ceruloplasmin ; Chaperonin Containing TCP-1 ; Clusterin ; Diagnosis ; Diagnosis, Differential ; Electrophoresis ; Fibroblasts ; Fibrosis ; Gelsolin ; Haptoglobins ; Humans ; Inflammation ; Lung Neoplasms ; Methods* ; Muramidase ; Pleural Effusion ; Pleural Effusion, Malignant ; Prevalence ; Proteomics ; Spectrum Analysis ; Tuberculosis ; Tuberculosis, Pleural

Adseverin is a Ca2+-dependent actin filament-severing protein that has been reported to regulate exocytosis via rearrangements of the actin cytoskeleton in secretory cells. However, the role of adseverin in bone cells has not yet been well characterized. Here, we investigated the role of adseverin in osteoclastogenesis using primary osteoclast precursor cells. Adseverin expression was upregulated during RANKL (receptor activator of nuclear factor-kappaB ligand)-induced osteoclast differentiation. Moreover, genetic silencing of adseverin decreased the number of osteoclasts generated by RANKL. Adseverin knockdown also suppressed the RANKL-mediated induction of nuclear factor of activated T-cell c1 (NFATc1), which is a key transcription factor in osteoclastogenesis. In addition, adseverin knockdown impaired bone resorption and the secretion of bone-degrading enzymes from osteoclasts. These effects were accompanied by decreased NFATc1 expression and the activation of nuclear factor-kappaB. Collectively, our results indicate that adseverin has a crucial role in osteoclastogenesis by regulating NFATc1.
Active Transport, Cell Nucleus ; Animals ; Bone Resorption/genetics/metabolism/pathology ; Cell Differentiation ; Cells, Cultured ; Female ; Gelsolin/genetics/*metabolism ; Gene Knockdown Techniques ; Humans ; Mice, Inbred ICR ; NF-kappa B/metabolism ; NFATC Transcription Factors/*metabolism ; Osteoclasts/*cytology/metabolism/pathology ; RANK Ligand/*metabolism