Gelsolin inhibits autophagy by regulating actin depolymerization in pancreatic ductal epithelial cells in acute pancreatitis

Gelsolin (GSN) can sever actin filaments associated with autophagy. This study investigated how GSN-regulated actin filaments control autophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP). AP was produced in a rat model and PDECs using caerulein (CAE). Rat pancreatic duct tissue and HPDE6-C7 cells were extracted at 6, 12, 24, and 48 h after CAE treatment. HPDE6-C7 cells in the presence of CAE were treated with cytochalasin B (CB) or silenced for GSN for 24 h. Pancreatic histopathology and serum amylase levels were analyzed. Cellular ultrastructure and autophagy in PDECs were observed by transmission electron microscopy after 24 h of CAE treatment. The expression of GSN and autophagy markers LC3, P62, and LAMP2 was evaluated in PDECs by immunohistochemistry and western blotting. Actin filaments were observed microscopically. Amylase levels were highest at 6 h of AP, and pancreatic tissue damage increased over time. Mitochondrial vacuolization and autophagy were observed in PDECs. CAE increased GSN expression in these cells over time, increased the LC3-II/LC3-I ratio and LAMP2 expression at 24 and 6 h of treatment, respectively, and decreased P62 expression at all time points. CB treatment for 24 h decreased the LC3-II/LC3-I ratio and LAMP2 expression, increased P62 levels, but had no impact on GSN expression in CAE-treated PDECs. CAE induced actin depolymerization, and CB potentiated this effect. GSN silencing increased the LC3-II/LC3-I ratio and LAMP2 expression and reduced actin depolymerization in CAE-treated PDECs. GSN may inhibit autophagosome biogenesis and autophagosome-lysosome fusion by increasing actin depolymerization in PDECs in AP.

The promising role of Gelsolin expression to predict survival in patients with squamous cell carcinoma of the larynx

Abstract Introduction: Gelsolin protein has important cellular functions, including cell motility and apoptosis. Altered gelsolin expression has been reported in several types of neoplasms, but clinicopathological features of gelsolin are currently unclear in patients with laryngeal squamous cell carcinoma. Objectives: Our aim is to investigate the clinicopathological significance of gelsolin as a prognostic biomarker for laryngeal squamous cell carcinoma. Methods: Tissue specimens from 168 patients with laryngeal squamous cell carcinoma were immunohistochemically assessed for the Gelsolin expression. Prognostic significance of Gelsolin and its interaction with clinical parameters was analysed. Results: Gelsolin expression was confirmed in 70.2% of cases. Gelsolin expression is significantly associated with tumor stage, tumor grade, and locoregional recurrence. Kaplan-Meier survival curves revealed that Gelsolin expression inversely correlated with both disease-specific and overall survival. Conclusion: This research is the first to demonstrate that Gelsolin expression is associated with a poor prognosis in laryngeal squamous cell carcinoma. Gelsolin is a novel promising biomarker and attractive target for the treatment of laryngeal squamous cell carcinoma.

The value of serum gelsolin, procalcitonin, homocysteine, cardiac troponin Iin diagnosis of multiple trauma severity and prognosis evaluating / 中国医师进修杂志

Objective:To analyze the value of serum gelsolin (GSN), procalcitonin(PCT), homocysteine (Hcy), cardiac troponin I(cTnI) in diagnosis of multiple trauma severity and prognosis evaluating.Methods:A retrospective analysis of 60 patients with multiple trauma from January 2019 to May 2020 in Liaocheng People′s Hospital were enrolled. According to injury severity score (SSA), the patients were divided into mild group (ISS ≤ 25 scores, 22 cases) and severe group (ISS>25 scores, 38 cases); according to prognosis, the patients were divided into survival group (38 cases) and death group(32 cases); 60 cases (control group) were included in the same period healthy volunteers. The levels of GSN, PCT, Hcy, cTnI were detected by enzyme-linked immunosorbent assay. The patients were followed up to 7 d, and the relationship between the above four serum items andinjury severity and survival rate were analyzed.Results:Before treatment, the level of GSN from low-to-high was severe group, mild group and control group; the levels of PCT, Hcy, cTnI from low-to-high was control group, mild group and severe group, and the differences were statistically significant ( P<0.05). After treatment, the level of GSN in mild group and severe group was increased, and the levels of PCT, Hcy, cTnI were decreased. Compared with those before treatment, the differences were statistically significant ( P<0.05). The level of GSN in the death group was lower than that in the survival group: (137.87 ± 9.54) mg/L vs. (190.32 ± 9.32) mg/L, the levels of PCT, Hcy, cTnI in the death group were higher than those in the survival group: (2.95 ± 0.32) μg/L vs. (0.44 ± 0.12) μg/L, (31.29 ± 8.54) μmol/L vs. (13.95 ± 2.19) μmol/L, (0.081 ± 0.007) μg/L vs.(0.020 ± 0.003) μg/L, and the differences were statistically significant ( P<0.05). The correlation analysis showed that the level of GSN had negative correlation with scale for the assessment of positive symptoms Ⅱ(SAPSⅡ) ( r = - 0.65, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)( r = - 0.74, P<0.05), and the levels of PCT, Hcy, cTnI had positive correlation with SAPSⅡ( r = 6.18, 7.09, 9.15, P<0.05) and APACHEⅡ( r = 6.93, 7.32, 10.03, P<0.05). Multiple-factor analysis showed that serum GSN was a protective factor for survival rate, and serum PCT, Hcy, and cTnI were risk factors for survival rate ( P<0.05). Conclusions:The levels of serum GSN, PCT, Hcy, CTNl can assist in judging the severity and prognosis of multiple trauma. It is recommended to use it in combination with SAPSⅡ and APACHEⅡ.

Changes of content and mRNA expression of gelsolin and proliferation activity of T-lymphocyte in spleen of mice with severe burn injury / 中华烧伤杂志

Objective@#To investigate the changes of content and mRNA expression of gelsolin and proliferation activity of T-lymphocyte in spleen of mice with severe burn injury, so as to determine the optimum intervention time of gelsolin.@*Methods@#Eighty male BALB/c mice were divided into sham injury group and burn group according to the random number table, with 40 mice in each group. Mice in burn group were inflicted with 15% total body surface area full-thickness scald (hereinafter referred to as burn) on the back. Immediately after injury, mice in burn group were hypodermic injected with 1 mL normal saline, with iodophor smeared on back once a day to prevent infection. Mice in sham injury group were sham injured without fluid infusion and smearing iodophor. At post injury hour (PIH) 0 (immediately), 8, 24, 48, and 72, spleen of 8 mice of each group were harvested aseptically, respectively. Proliferation activity of T-lymphocyte was determined with methyl-thiazolyl-tetrazolium colorimetry method; gelsolin content of spleen was determined with enzyme-linked immunosorbent assay; mRNA expression of gelsolin of spleen was determined with real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were processed with analysis of variance of factorial design, one-way analysis of variance, LSD test and Bonferroni correction.@*Results@#(1) There was no significant difference in proliferation activity of T-lymphocyte in spleen of mice in two groups at PIH 0 (P>0.05). Proliferation activity of T-lymphocyte in spleen of mice in sham injury group was significantly higher than that in burn group at PIH 8, 24, 48, and 72 (with P values below 0.05). There was no significant difference in proliferation activity of T-lymphocyte in spleen of mice in sham injury group at each time point post injury (F=0.756, P>0.05). Proliferation activity of T-lymphocyte in spleen of mice in burn group at PIH 8 was 0.12±0.04, significantly lower than that at PIH 0, 24, 48, and 72 in the same group (0.73±0.07, 0.56±0.07, 0.51±0.09, and 0.59±0.07, respectively, with P values below 0.05). (2) There was no significant difference in gelsolin content of spleen of mice in two groups at PIH 0 (P>0.05). Gelsolin content of spleen of mice in sham injury group was significantly higher than that in burn group at PIH 8, 24, 48, and 72 (with P values below 0.05). There was no significant difference in gelsolin content of spleen of mice in sham injury group at each time point post injury (F=1.083, P>0.05). Gelsolin content of spleen of mice in burn group at PIH 8 was (11.9±2.6) pg/mg, significantly lower than that at PIH 0, 24, 48, and 72 in the same group [(37.7±2.9), (19.9±4.0), (24.1±4.1), and (24.6±4.0) pg/mg, respectively, with P values below 0.05]. (3) There was no significant difference in mRNA expression of gelsolin of spleen of mice in two groups at PIH 0 (P>0.05). The mRNA expressions of gelsolin of spleen of mice in sham injury group were significantly higher than those in burn group at PIH 8, 24, 48, and 72 (with P values below 0.05). There was no significant difference in mRNA expression of gelsolin of spleen of mice in sham injury group at each time point post injury (F=0.413, P>0.05). The mRNA expression of gelsolin of spleen of mice in burn group at PIH 8 was 0.307±0.064, significantly lower than that at PIH 0, 24, 48, and 72 in the same group (0.944±0.023, 0.625±0.091, 0.744±0.104, and 0.821±0.072, respectively, with P values below 0.05).@*Conclusions@#Severe burn injury could induce decrease of proliferation activity of T-lymphocyte and content and mRNA expressions of gelsolin in spleen of mice, and all of them decreased into the lowest at PIH 8. Optimum intervention time of gelsolin for severe burn would be before PIH 8.

Identification of novel biomarkers for adult-onset-immunodeficiency (AOID) syndrome using serum proteomics

OBJECTIVE@#To identify the candidate protein biomarkers of adult-onset-immunodeficiency (AOID) syndrome using serum proteomics.@*METHODS@#Screening and verification phases were performed in the study. A total of 97 serum samples were classified into three groups: AOID patients with opportunistic infections (active AOID), AOID patients without opportunistic infections (inactive AOID), and healthy control. In the screening phase, pooled sera collected from patients and healthy control in each group were separated by 2D-gel electrophoresis, analyzed for differentially expressed proteins and identified for biomarkers using LC/MS. In the verification phase, the protein candidates were selected for confirmation by western blotting.@*RESULTS@#The analysis revealed 35 differentially expressed proteins. Three proteins including haptoglobin, gelsolin, and transthyretin, were selected for verification. The results showed that the levels of haptoglobin in both active and inactive AOID groups were significantly higher than that in the control group, while the levels of gelsolin in the active AOID group were significantly lower than that in the inactive AOID group. The level of transthyretin in the active AOID group was also significantly lower than that in the control group.@*CONCLUSIONS@#The comparison of serum proteins between the three groups revealed three candidates which are related to chronic inflammatory diseases. Haptoglobin and transthyretin biomarkers could be applied in clinical assessment for monitor of disease outcome, including for the study of AOID pathogenesis.

Prepartation of Gelsolin-targeted ultrasound contrast agent and experiment in vitro / 中国医学影像技术

Objective To prepare a kind of Gelsolin-targeted ultrasound contrast agent (GSN-PLGA) and to explore its targeting and imaging effection in vitro.Methods The high molecular PLGA-COOH ultrasound contrast agents were prepared by a modified double emulsion technique and then conjugated with Gelsolin monoclonal antibody by carbodiimide technique.The physical property of contrast agent was determined.And the connectivity condition of ultrasound contrast agent with Gelsolin monoclonal antibody was estimated.The targeting ability and the effect of enhancing ultrasound imaging in vitro were explored.Results The average diameter of GSN-PLGA was (575.67 ± 4.71) nm.The potential was (-11.46±1.19) mV.And the binding rate of Gelsolin monoclonal antibody was 96.93％.In vitro experimentshowed more GSN-PLGA could be intaked by Hca-F cells and the ultrasound imaging cloud be enhanced greatly.Conclusion The GSN-PLGA nanoparticle can bind to Hca-F cells specifically and can enhance the ultrasound imaging greatly.

Identification of novel biomarkers for adult-onset-immunodeficiency (AOID) syndrome using serum proteomics

Objective To identify the candidate protein biomarkers of adult-onset-immunodeficiency (AOID) syndrome using serum proteomics. Methods Screening and verification phases were performed in the study. A total of 97 serum samples were classified into three groups: AOID patients with opportunistic infections (active AOID), AOID patients without opportunistic infections (inactive AOID), and healthy control. In the screening phase, pooled sera collected from patients and healthy control in each group were separated by 2D-gel electrophoresis, analyzed for differentially expressed proteins and identified for biomarkers using LC/MS. In the verification phase, the protein candidates were selected for confirmation by western blotting. Results The analysis revealed 35 differentially expressed proteins. Three proteins including haptoglobin, gelsolin, and transthyretin, were selected for verification. The results showed that the levels of haptoglobin in both active and inactive AOID groups were significantly higher than that in the control group, while the levels of gelsolin in the active AOID group were significantly lower than that in the inactive AOID group. The level of transthyretin in the active AOID group was also significantly lower than that in the control group. Conclusions The comparison of serum proteins between the three groups revealed three candidates which are related to chronic inflammatory diseases. Haptoglobin and transthyretin biomarkers could be applied in clinical assessment for monitor of disease outcome, including for the study of AOID pathogenesis.

Plasma gelsolin levels in prediction of prognosis of ST-segment elevation myocardial infarction / 中国介入心脏病学杂志

Objective To investigate the predictive value of plasma gelsolin in the prognosis of patients with ST-sgement elevation myocardial infarction ( STEMI ) and undergone primary percutaneous coronary intervention ( PCI ) .Methods The study included 206 patients with STEMI and undergone primary PCI, 148 patients with stable angina pectoris and received elective PCI and 80 healthy volunteer as the health population (NP) control.Blood samples were taken at admission on day 1, 3, 5, 7 and 9 to determine the plasma gelsolin level .Patients′baseline clinical characteristics , blood biochemistry tests results , details of operation and their cardiovascular risk factors were recorded .Major adverse cardiovascular events (MACE) within one year were recorded.Results (1) Compared to the stable angina group and the NP group, the level of plasma gelsolin of STEMI patients were obviously decreased at various time points ( all P<0.05 ) .There were no statistical differences between the stable angina group and the NP group .( 2 ) Patients with STEMI were catagorized into MACE group (n=78) and non-MACE group (n=128) according their follow up record in 1 year.The level of plasma gelsolin in patients with MACE were lower than the non-MACE group ( P <0.05 ) with the minimum value detected on day 7.Among patients complicated with MACE (n=78), they were further devided into the deceased group (n=18) and the survival group (n=60).Plasma gelsolin levels were lower in the deceased group with satistical differences found on day 5, 7 and 9.(3) Single factor Logistic regression analysis showed that the level of plasma gelsolin on day 7 was independent risk factor of MACE within one year ( P =0.014 ) .( 4 ) Setting the cutoff value of plasma gelsolin on day 7 as 21.7 mg/L,the sensitivity and speciticity for the MACE in STEMI patients treated with primary PCI within one year were 82.1%and 81.4%respectively , with the area under the receiver operator characteristic curve ( ROC ) was 0.854 ( 95% confidence interval 0.732 -0.961 , P <0.01 ) . Conclusions Plasma gelsolin levels are correlated with the severity of STEMI lesions and plasma gelsolin can be used as predicting factor of prognosis .

The value of gelsolin for evaluating the prognosis of patients with severe sepsis / 中华急诊医学杂志

Objective To evaluate the value of gelsolin for the prognosis of patients with severe sepsis.Methods 50 patients in the emergency intensive care unit of Beijing hospital from January 2015 to July 2015,were determined white blood cell count (WBC),C-reactive protein (CRP),procalcitonin (PCT),gelsolin at admission,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score were estimated within 24 hours.According to the 28 days of survival outcome,50 patients were divided into two groups:survival group and death group.The significant difference of these factors was compared.Binary logistic regression analysis was applied for screening independent risk factors for the prediction of death.The receiver operating characteristic (ROC) curve was applied for the evaluation and comparison about prognosis ability.Results 31 patients were in the survival group,19 patients in the death group.The gelsolin [(21.43±10.54) vs.(13.31±8.54),P=0.007] andAPACHE Ⅱ score [(19.2±6.86) vs.(24.6 ± 8.9),P =0.021] in two groups had significance difference.Binary logistic regression analysis indicated that the gelsolin and APACHE Ⅱ score were independent risk factors of predicting death.The area under of ROC curve (AUC) of the gelsolin was 0.745 (95％ CI:0.599-0.851,P =0.004) and the APACHE Ⅱ score was 0.699 (95％ CI:0.537-0.862,P =0.019).Both prognosis ability were equivalent.To combine the tow factors,the accuracy of predition was 90％ and has better complementarity.Conclusions the gelsolin could assess the severity of patients with severe sepsis and predict the prognosis more accurately.

The First Korean Family With Hereditary Gelsolin Amyloidosis Caused by p.D214Y Mutation in the GSN Gene

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.

Actin Scavenging System and Coagulation-fibrinolytic System in Peripheral Blood of Pre-eclampsia Patients / 中国医科大学学报

Objective To detect the levels of plasma gelsolin(GSN),vitamin D binding protein(VDBP)and coagulation?related parameters in peripheral blood between pre?eclampsia,then analyze their relationships with the onset or development of pre?eclampsia. Methods A total of 30 women with severe pre?eclampsia(SPE)and 30 women with mild pre?eclampsia(MPE)were enrolled for the study and randomly chosen as trial group. 30 normal pregnancies with matching gestational ages were selected as control group?1 and 30 normal full?term pregnancies were randomly chosen as control group?2. The levels of GSN,VDBP,platelet(PLT),prothrombin time(PT),thrombin time(TT),activated partial thromboplas?tin time(APTT),fibrinogen(FIB),and D?dimer were compared between those groups. Results The levels of GSN,VDBP and PLT,PT,APTT, FIB in SPE group were significantly lower than that of MPE group(P0.05). There were no statistical difference among all the levels of coagulation?related parameters in healthy pregnant women(P>0.05). Conclusion GSN and VDBP levels in pre?eclampsia are significantly lower than that of normal pregnant women,along with pathological hy?percoagulative state,and which are related to severity of disease.

Lattice Corneal Dystrophy, Gelsolin Type: The First Case Report in Korea

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.

Prognostic significance of gelsolin and MMP12 in Langerhans cell histiocytosis

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.

Danish type gelsolin-related amyloidosis in a Brazilian family: case reports / Amiloidose familiar relacionada ao gene gelsolin em uma família brasileira: relato de casos

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systemic amyloidosis showing marked geographic clustering in Finland. The disease is caused by a point mutation, 654G-A, in the gelsolin gene. The Danish-subtype of FAF has been previously described in three families, the patients present clinical findings similar to FAF, and the mutation 654G-T in the gelsolin gene. Three members from two generations of the same family, with familial amyloidosis, were screened for mutations in the GSN gene. Genomic DNA was extracted from peripheral blood lymphocytes and the polymerase chain reaction (PCR) was carried out under standard conditions, using appropriate primers. Sequence analysis showed the presence of a G to T transition at nucleotide 654 of the gelsolin gene. This is the first report of gelsolin-related familial amyloidosis in a Brazilian family, and the result is particularly significant as this pedigree presents an unusual mutation, described previously in three families, with no known Finnish ancestors (Danish type).

Amiloidose familiar do tipo finlandes (FAF) é uma forma de amiloidose sistêmica autossômica dominante com grande concentração geográfica na Finlândia. É causada por uma mutação, 654G-A, no gene gelsolin. O subtipo dinamarquês da FAF foi previamente descrito em três famílias, com achados clínicos similares mas com a mutação 654G-T no gene gelsolin. Três membros de duas gerações da mesma família, com diagnóstico de amiloidose familiar, foram submetidos a screening de mutações no gene gelsolin. O DNA genômico foi extraído de linfócitos do sangue periférico, sendo realizada reação em cadeia de polimerase (PCR) em condições padronizadas. A análise do sequenciamento revelou uma transição de G para T no nucleotidio 654 do gene gelsolin. Este é o primeiro relato de uma amiloidose familiar relacionada ao gene gelsolin em uma família brasileira, que apresenta uma forma rara de mutação, descrita previamente em três famílias, sem ancestrais finlandeses (tipo dinamarquês).

Gelsolin level for evaluating severity and prognosis in patients at critically ill / 中华全科医师杂志

Objective To investigate clinical value of gelsoin level for evaluating severity and prognosis in patients with critical illness. Methods Forty-eight patients with critical illness admitted to the Emergency Intensive Care Unit of Beijing Hospital during February to December 2008 were enrolled in this study, with 23 survivors and 25 deaths. Serum level of gelsolin was measured for 31 of them at least twice during their hospital stay, and for other 17 only once at their admission. They all were evaluated with acute physiology and chronic health evaluation Ⅱ ( APACHE Ⅱ ) scores within 24 hours after admission. In addition, serum level of gelsolin was measured for another 307 healthy adults as controls. Results Initial level of gelsolin was significantly lower in 48 patients at critically ill than that in controls [(24 ± 11) mg/L vs. (192 ±39) mg/L, P < 0. 01]. There was significant difference in initial level of gelsolin between surviving group (23 cases) and death group (25 cases) [(28 ± 10) mg/L vs. (21 ±12) mg/L, P = 0. 033]. Fatality of patients at critically ill increased as their level of gelsolin at 22 mg/L or less, with a predicting accuracy of 74. 19% , as well as decreasing trend of their gelsolin levels in continuously minitoring, with a predicting accuracy of 70. 97%. Predicting accuracy of APACHE Ⅱ scores of 30 or more was 67.74%. However, predicting accuracy would reach 93.55% as final level of gelsolin and its decreasing trend combined with APACHE Ⅱ scores in prognostic assessment for critically ill patients. Conclusions Severity of patients at critically ill can be predicted by their gelsolin level, especially in continuously monitoring, which is an indicator better than APACHE Ⅱ scores. Combination of gelsolin level with APACHE Ⅱ scores shows a more accurate prognostic assessment for critically ill patients.

Expression change of hepatic gelsolin and potential effect of Xuebijing injection in septic rats / 中华创伤杂志

Objective To investigate the expression changes of hepatic gelsolin (GSN) and the potential effect of traditional Chinese medicine Xuebijing injection in septic rats. Methods A total of 104 male Wistar rats were randomly divided into four groups, ie, normal control group (n = 8), sham operation group (n = 32), cecal ligation and puncture group (CLP group, n = 32) and Xuebijing treatment group (n = 32). The sepsis animal models in the last two groups were developed by CLP. In Xuebijing treatment group, animals were treated intravenously with Xuebijing injection (4 ml/kg) at 2, 12, 24,36, 48 and 60 hours after operation, respectively. Animals were sacrificed respectively at 6, 12, 24, and 72 hours after operation to harvest blood and hepatic tissue samples. Markers of liver function, contents of GSN and Gc globulin and expression of GSN mRNA in the liver tissues were detected. Results Compared with normal control group and sham operation group, hepatic GSN content was decreased significantly at various intervals in CLP group (P ＜ 0. 05), which reached the lowest value of (1.42 ±0.50) ng/mg at 12 hours. Meanwhile, expression of GSN mRNA in the liver was markedly enhanced at six hours after CLP and remained a high value until 72 hours, compared with the sham operation group (1.203±0.053 vs 1.030 ±0.084, P ＜0.05). Similarly, the hepatic Gc globulin contents was increased in the CLP group compared with the normal control group and sham operation group (P ＜ 0.05).After treatment with Xuebijing injection, the hepatic GSN contents at 6-72 hours was increased gradually while serum ALT and AST levels at 6, 12 and 24 hours were reduced significantly in comparison to the CLP group (P ＜ 0.05). Nevertheless, treatment with Xuebijing injection showed no marked effect on hepatic GSN mRNA expression and Gc globulin release (P ＞ 0.05). Conclusions Hepatic GSN contents are persistently reduced in the development of sepsis and treatment with Xuebijing injection can markedly attenuate acute liver injury through increasing GSN contents in severe sepsis.

Degradation of gelsolin in pancreatic cancer cell lines by ubiquitin-proteasome pathway / 基础医学与临床

Objective To explore the role of ubiquitin-proteasome pathway for the gelsolin protein degradation in pancreatic cancer.Methods Pancreatic cancer cell lines BxPC-3 and PANC-1 were first treated with specific 26s proteasome inhibitor lactacystin.Immunoblots of cell lysates were probed for gelsolin expression.To determine whether gelsolin was conjugated to ubiquitin,proteins extracted from the cells with or without lactacystin were immunoprecipitated with anti-gelsolin antibody,followed by Western blot analysis.Results The expression of gelsolin protein increased obviously after treatment with lactacystin in BxPC-3 cells for 12 h.Using anti-gelsolin antibody to immunoprecipitate gelsolin protein and followed by Western blot using anti-ubiquitin monoclonal antibody,it was found that inhibition of proteasome pathway by lactacystin resulted in accumulation of ubiquitylated forms of gelsolin protein.In PANC-1 cell line,there was no significant changes of gelsolin after treatment with lactacystin.Conclusion Ubiquitin-proteasome dependent degradation may be an important regulatory mechanism for gelsolin down-regulation in pancreatic cancer cells.