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Abstract Objectives: Observational studies suggested that obesity may promote the development of allergic rhinitis. The aim of this study was to explore the association of obesity, lipids and adipokines with this allergic disease at the genetic level using Mendelian randomization strategies. Methods: Summary data for three obesity indicators (such as body mass index), eight lipid indicators (such as triglycerides) and six adipokines (such as interleukin-6 and adipocyte fatty acid-binding protein) were collected, and suitable instrumental variables were extracted from these summary data according to the three main assumptions of Mendelian randomization. Three Mendelian randomization methods (such as inverse variance weighted) were used to detect the casual effect of the above indicators on allergic rhinitis risk. Sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. Results: After Bonferroni correction, the inverse variance weighted reported that elevated levels of interleukin-6 and adipocyte fatty acid-binding protein were nominally associated with the decreased risk of allergic rhinitis (OR = 0.870, 95% CI 0.765-0.990, p = 0.035; OR = 0.732, 95% CI 0.551-0.973, p = 0.032). The other Mendelian randomization methods supported these results. Obesity, lipids and other adipokines were not related to this allergic disease. Sensitivity analyses found no heterogeneity and horizontal pleiotropy in the study. Conclusion: The study provided some interesting, but not sufficient, evidence to suggest that interleukin-6 and adipocyte fatty acid-binding protein might play a protective role in the development of allergic rhinitis at the genetic level. These findings should be validated by more research. Level of evidence: This was a Mendelian randomized study with a level of evidence second only to clinical randomized trials, and higher than cohort and case-control studies.
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Objective:To investigate the effects of down-regulation of FABP5 (fatty acid binding protein 5) on radiation damage of skin cells, and explore underlying mechanism.Methods:A lentiviral vector with down-regulated FABP5 was constructed to infect human immortalized keratinocytes (HaCaT) cells, and the transfection efficiency was examined. The HaCaT cells were divided into blank control group, FABP5 down-regulation group (FABP5), radiation group (IR), and FABP5 down-regulation combined with radiation group (FABP5+ IR). After 6 MV X-ray radiation, cell proliferation viability was measured by CCK-8 assay, cell migration was detected by scratch assay, apoptosis was analyzed by flow cytometry, radiosensitivity was evaluated by cloning formation assay, and the cellular protein expressions of PARP1, γ-H2AX, AKT and p-AKT were detected by Western blot.Results:FABP5 was successfully knocked-down in both RNA level ( t=25.14, P<0.05) and protein level ( t=20.06, P<0.05). The down-regulation of FABP5 decreased the abilities of cells proliferation ( t=3.55, 5.88, 3.18, P<0.05) and migration ( t=15.44, P<0.05), but increased cell resistance to irradiation with a radiosensitization ratio of 0.782. The apoptosis rate of FABP5+ IR group was significantly lower than IR group (22.05±6.71)% vs. (9.82±1.45)%, t=3.08, P<0.05. The protein levels of PARP1 and γ-H2AX in FABP5+ IR group were also lower than those in the IR group 0.04±0.04, 0.11±0.06, 0.26±0.11, 0.22±0.07, 0.21±0.10, 0.52±0.22, 0.57±0.06, 0.43±0.02( t=2.83, 3.07, 4.50, 5.33, P<0.05), while the protein level of p-Akt in FABP5+ IR group was higher than that in IR group ( t=-16.24—3.02, P<0.05). Conclusions:Down-regulation of FABP5 inhibited cell proliferation and migration, increased radioresistance, and reduced radiation-induced apoptosis and DNA damage of skin cells probably through PI3K/AKT signaling pathway.
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Objective:To analyze the value of serum related cytokines in predicting intestinal mucosal injury in patients with severe acute pancreatitis (SAP) and its correlation with intestinal mucosal injury.Methods:A total of 92 patients with SAP admitted to the First Hospital of Qinhuangdao from January 2020 to December 2021 were included in the study. According to the presence or absence of intestinal mucosal barrier dysfunction, the patients were divided into intestinal mucosal barrier dysfunction group (33 cases) and non-intestinal mucosal barrier dysfunction group (59 cases). Another 100 healthy subjects were selected as the control group. Clinical data of the subjects were collected. Serum levels of procalcitonin (PCT), D-lactic acid (D-L), endotoxin, diamine oxidase (DAO), citrulline and intestinal fatty acid binding protein (I-FABP) of the three groups were compared, and the correlation between the above indexes was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the value of each indicator in predicting intestinal mucosal barrier dysfunction in SAP patients.Results:The levels of serum PCT, D-L, endotoxin, DAO and I-FABP in intestinal mucosal barrier dysfunction group, non-intestinal mucosal barrier dysfunction group and control group showed a downward trend, while the level of serum citrulline showed an upward trend, with statistically significant difference (all P<0.05). Pearson correlation analysis showed that serum citrulline was negatively correlated with serum PCT, D-L, and endotoxin levels ( r=-0.740, -0.629, -0.310, all P<0.05); There was a positive correlation between serum DAO and serum PCT, D-L and endotoxin levels ( r=0.482, 0.779, 0.338, all P<0.05); There was a positive correlation between serum I-FABP and serum PCT, D-L and endotoxin levels ( r=0.613, 0.421, 0.341, all P<0.05). The ROC curve results showed that the area under the curve (AUC) of serum PCT, D-L, endotoxin, DAO, citrulline, and I-FABP predicting intestinal mucosal injury in SAP patients were 0.816, 0.789, 0.732, 0.801, 0.812, and 0.857, respectively. The AUC of the combination of the above indicators predicting intestinal mucosal barrier dysfunction in SAP patients was 0.909, significantly higher than that predicted by each index alone (all P<0.05). Conclusions:The occurrence of intestinal mucosal barrier dysfunction in SAP patients may be related to the increase of serum PCT, D-L, endotoxin, DAO, I-FABP levels and the decrease of citrulline levels. It may be considered to predict the risk of intestinal mucosal injury by detecting the levels of various indicators in patients′ serum.
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Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.
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Objective:To discuss the value of dynamic detection of serum intestinal fatty acid binding protein (I-FABP), heparin binding protein (HBP) and interleukin-1β(IL-1β) in early predicting and evaluating the severity of abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP) postoperative patients.Methods:The clinical data of 65 SAP patients treated in the Second Hospital of Anhui Medical University from July 2019 to Jan 2021 were retrospective analyzed. According to whether ACS has occurred, the patients were divided into non ACS group (48 cases) and ACS group (17 cases). The serum I-FABP, HBP and IL-1β of the two groups were dynamically monitored. Correlation analysis and receiver operating characteristic (ROC) curve were used to evaluate the efficacy and early prediction value of each observation index in evaluating the severity of SAP patients complicated with ACS.Results:There were no significant differences in age, sex, body mass index (BMI) and pathogenesis between the two groups (all P>0.05). The serum levels of C-reactive protein (CRP), white blood cell (WBC), Acute Physiology and Chronic Health Enquiry (APACHE-Ⅱ) score and intra-abdominal pressure (IAP) in ACS group were significantly higher than those in non ACS group (all P<0.05). The serum levels of I-FABP [(97.41±15.02)ng/ml vs (37.28±18.34)ng/ml, (103.32±18.40)ng/ml vs (56.96±19.12)ng/ml, (85.69±22.94)ng/ml vs (36.88±10.49)ng/ml], HBP [(92.19±14.59)ng/ml vs (24.56±10.96)ng/ml, (106.11±15.03)ng/ml vs (37.17±13.83)ng/ml, (128.11±16.43)ng/ml vs (68.94±15.91)ng/ml] and IL-1β[(15.78±1.44)pg/ml vs (11.26±1.34)pg/ml, (19.34±1.87)pg/ml vs (13.51±2.84)pg/ml, (20.95±1.96)pg/ml vs (16.03±1.04)pg/ml] on 1st, 4th, 7th day in ACS group were continuously and evidently higher than those in non ACS group ( P<0.01). Correlation analysis revealed that I-FABP, HBP and IL-1β were positively correlated with IAP ( r=0.745, 0.793, 0.770) and APACHE Ⅱ score ( r=0.510, 0.489, 0.445) (all P<0.01). ROC curve analysis showed that the AUC of early prediction by I-FABP, HBP and IL-1β on the occurrence of ACS were 0.846, 0.873 and 0.902 respectively, which were higher than the CRP (0.681), WBC (0.765) and APACHE Ⅱ score (0.795), the sensitivity and specificity can be significantly improved to 0.997 and 0.994 by parallel and series tests respectively combined with the three indicators. Conclusions:Dynamic detection of serum I-FABP, HBP and IL-1β has a certain clinical value in evaluating the severity of ACS in SAP patients. At the same time, early detection with serum I-FABP, HBP and IL-1β has high predictive power for ACS in SAP patients and the combined application of three has higher predictive value.
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Objective:To explore the correlation between serum adipocyte fatty acid binding protein 4 (FABP4) and peroxisome proliferator activated receptor gamma (PPAR gamma) levels and metabolism related fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) .Methods:230 patients with T2DM and MAFLD in Zhangjiakou First Hospital from Feb. 2019 to Feb. 2021 were selected. According to their disease conditions, 80 patients with T2DM and without MAFLD were set as simple T2DM group, 78 patients with MAFLD and normal glucose tolerance were set as simple MAFLD group, 72 patients with T2DM and MAFLD were set as T2DM and MAFLD group, and 100 healthy volunteers in the same period were selected as the control group.Results:The levels of HOMA-IR and FABP4 in T2DM patients were significantly higher than those in the control group ( P<0.05) , while the levels of HDL-C, crea and PPAR γ in T2DM grou were significantly lower than those in the control group ( P<0.05) . The levels of BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 in MAFLD group were significantly higher than those in control group ( P<0.05) , while the level of PPAR γ in MAFLD group was significantly lower than that in control group ( P<0.05) . BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 of T2DM patients with MAFLD were significantly higher than those of T2DM patients without MAFLD and control group ( P<0.05) , while HDL-C and PPAR γ were significantly lower than those of T2DM patients without MAFLD and control group ( P<0.05) . HOMA-IR and FABP4 in T2DM patients with MAFLD were significantly higher than those in MAFLD group ( P<0.05) , while HDL-C, crea and PPAR γ were significantly lower than those in MAFLD group ( P<0.05) . FABP4 was positively correlated with HOMA-IR and CREA (all P<0.05) , and negatively correlated with HDL-Cand PPAR γ (all P<0.05) . PPAR γ was positively correlated with TG and ALT (all P<0.05) , and negatively correlated with HOMA-IR ( P<0.05) . Alt, TG, HOMA-IR, FABP4 and PPAR γ were independent risk factors for MAFLD in T2DM patients ( P<0.05) . Conclusion:FABP4 is positively correlated with the occurrence of T2DM and MAFLD, PPAR γ is negatively correlated with the occurrence of T2DM and MAFLD, the negative feedback loop regulation of FABP4 and PPAR γ can cause the occurrence of insulin resistance, so as to improve the risk of T2DM combined with MAFLD, and provide clinical basis for clinical disease prevention and treatment.
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Background Silicosis is caused by long-term inhalation of large amounts of free silica (SiO2) particles, and exploring its mechanism can provide new directions for the treatment of silicosis fibrosis. Objective To investigate the expression and role of fatty acid binding protein 5 (FABP5) in a silica-induced silicosis model. Methods In combination with the results of single-cell transcriptome sequencing, the expression pattern of FABP5 in mouse alveolar epithelial cells was explored by bioinformatic analysis, and the distribution pattern of fabp5 was detected by spatial transcriptomics. An in vivo model of silicosis was established by intratracheal injection with SiO2 into mice and four groups were set up: normal saline (NS) 7 d group, NS 56 d group, SiO2 7 d group, and SiO2 56 d group. An in vitro model of silicosis was established in SiO2-treated mouse lung epithelial cell line (MLE-12). At the whole animal level, the marker of epithelial cells (E-Cad) and the protein level of FABP5 were detected by tissue immunofluorescence assay; in vitro, the changes of fabp5 mRNA expression and protein level in MLE-12. Results The results of single-cell transcriptome sequencing and spatial transcriptome sequencing showed that the mRNA expression of fabp5 was upregulated in type II alveolar epithelial cells in the focal area of silicosis in mice, accompanied by elevated tissue immunofluorescent protein levels, and there was co-localization of E-CAD. Meanwhile, SiO2 stimulation induced a 1.58-fold increase in fabp5 mRNA expression and a 2-fold increase in protein levels in MLE-12 cells, with significant differences (P<0.05). Conclusion The protein level of FABP5 is increased in alveolar epithelial cells in a pulmonary fibrosis model, suggesting that FABP5 may be involved in the pathological process of epithelial cells in pulmonary fibrosis.
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Objective:To explore the influence of microRNA (miRNA)-6751-3p expression on the proliferation and migration of gastric cancer cells and its molecular mechanism.Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of miR-6751-3p in gastric cancer cell lines (MGC803, BGC823, SGC7901, HS-746T) and normal gastric mucosal epithelial cells (GES-1). The gastric cancer cell lines with the lowest expression level of miR-6751-3p were divided into control group and experimental group, and were transfected with miR-NC and miR-6751-3p mimics respectively. qRT-PCR detected the expression level of miR-6751-3p in the two groups of cells. CCK-8 method and scratch healing test were used to detect the proliferation and migration of miR-6751-3p overexpressing cells. The potential target genes of miR-6751-3p were predicted through Deepbase v2.0 and microRNA.org online websites, and the dual luciferase reporter gene experiment was used to verify. qRT-PCR and Western blot were used to detect the expression of target genes in miR-6751-3p overexpression cells.Results:Compared with normal gastric mucosal epithelial cells, the expression of miR-6751-3p was significantly down-regulated in gastric cancer cell lines ( P<0.05), and the cell line with the lowest expression level was MGC803 cells ( P<0.01). Compared with the control group, overexpression of miR-6751-3p can inhibit the proliferation ability ( P<0.05). The scratch healing rate of MGC803 cells in the control group and the experimental group were (65.14±5.65)% and (23.40±6.78)%, respectively. Compared with the control group, the scratch healing rate of MGC803 cells in the experimental group was significantly lower ( t=4.73, P<0.01). The online website predicts that the target gene of miR-6751-3p may be fatty acid binding protein 5 ( FABP5), and miR-6751-3p can complementally bind FABP5 messenger RNA (mRNA) ( t=4.01, P<0.01). Compared with the control group, overexpression of miR-6751-3p can inhibit the expression of FABP5 gene in MGC803 cells ( P<0.01). Conclusion:The expression of miR-6751-3p in gastric cancer cell lines is low, and the overexpression of miR-6751-3p can inhibit the proliferation and migration of gastric cancer MGC803 cells by down-regulating the FABP5 gene.
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OBJECTIVES@#To investigate the relationship between the fatty acid-binding protein 4 (FABP4) and colorectal cancer (CRC).@*METHODS@#Using an enzyme-linked immunosorbent assay (ELISA), we measured the expression of FABP4 in plasma of 50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls. The content of the visceral fat area (VFA) as seen with abdominal computed tomography (CT) scanning was measured by ImageJ software. The expression levels of FABP4, E-cadherin, and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.@*RESULTS@#The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group (22.46 vs. 9.82 ng/mL; @*CONCLUSIONS@#High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients. FABP4 protein was highly expressed in CRC tissues and associated with TNM stage, differentiation, and lymph node metastasis of CRC. The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression, suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition (EMT).
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Objective:To investigate the correlation of intestinal fatty acid binding protein and diamine oxidase with intestinal injury in strangulated bowel obstruction mice.Methods:160 SD rats were divided into 5 groups by random number table: group A ( n=32) : normal control group; group B ( n=32) : sham operation group; group C ( n=32) : simple intestinal obstruction group; The strangulated intestinal obstruction group was divided into group D ( n=32) : acute superior mesenteric artery ischemia group and group E ( n=32) : acute mesenteric arterial and venous ischemia. Except group A, other groups were given operation for modeling. Venous blood and small intestinal segment of group A was collected after anaesthesia, and venous blood and small intestinal segment of other groups were collected after modeling for 4 h. Serum samples were collected from venous blood, and intestinal fluid samples were collected by soaking the small intestinal segments. The intestinal segments were observed and the intestinal injury was evaluated. The levels of intestinal fatty acid binding protein (I-FABP) and activity of diamine oxidase (DAO) in serum and intestinal fluid were detected. Pearson correlation analysis was used to analyze the correlation between intestinal injury and the serum and intestinal fluid levels of I-FABP and activity of DAO, respectively. Results:The intestinal damage scores in group B, C, D and E were higher than that in group A, the intestinal damage scores in groups C, D and E were higher than that in group B, the intestinal damage scores in groups D and E were higher than that in group C, and the intestinal damage score in group E was higher than that in group D ( P<0.05) . The serum I-FABP level and DAO activity in group C, D and E were higher than those in group A and B, and the serum I-FABP level and DAO activity in group D and E were higher than those in group C ( P<0.05) . The level of I-FABP and DAO activity in intestinal fluid in group C, D and E were higher than those in groups A and B, and the level of I-FABP and DAO activity in intestinal fluid in group D and E were higher than those in group C ( P<0.05) . There were positive correlations between intestinal injury and the serum and intestinal fluid levels of I-FABP and activity of DAO, respectively ( r=0.972, P<0.001; r=0.899, P<0.001; r=0.961, P<0.001; r=0.828, P<0.001) . Conclusions:Intestinal injury of strangulated bowel obstruction mice is related to the intestinal ischmia. There are increases of serum and intestinal fluid levels of I-FABP and activity of DAO in strangulated bowel obstruction mice, which are closely related to the degree of intestinal injury.
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Objective To explore the feasibility of biomarkers in static cold storage (SCS) perfusate of donor kidney from donation after cardiac death (DCD) for predicting delayed graft function (DGF) after renal transplantation. Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed. All recipients were divided into the DGF group (n=7) and immediate graft function (IGF) group (n=57) according to the incidence of postoperative DGF in the recipients. The levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), interleukin -18(IL-18) and kidney injury molecule-1 (KIM-1) in the SCS perfusate were statistically compared between two groups, and the correlation with DGF was analyzed. The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed. Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11% (7/64). The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group (P=0.009). The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation (r=0.430, P < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation (both P < 0.05). The area under the curve (AUC) of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932 [95% confidence interval (CI) 0.850-1.000]. The sensitivity was calculated as 1.000 and 0.754 for the specificity (P < 0.05). Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation. Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.
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Objective To observe the skin ultrastructure change of electric shock death rats and to test the expression changes of hypoxia-inducible factor-2α （HIF-2α） and heart type-fatty acid-binding protein （H-FABP） of myocardial cells, in order to provide basis for forensic identification of electric shock death. Methods The electric shock model of rats was established. The 72 rats were randomly divided into control group, electric shock death group and postmortem electric shock group. Each group was divided into three subgroups, immediate （0 min）, 30 min and 60 min after death. The skin changes of rats were observed by HE staining, the changes of skin ultrastructure were observed by scanning electron microscopy, and the expression of HIF-2α and H-FABP in rats myocardium was tested by immunohistochemical staining. Results The skin in the electric shock death group and postmortem electric shock group had no significant difference through the naked eye or by HE staining. Under the scanning electron microscope, a large number of cellular debris, cells with unclear boundaries, withered cracks, circular or elliptical holes scattered on the cell surface and irregular edges were observed. A large number of spherical foreign body particles were observed. Compared with the control group, the expression of HIF-2α in all electric shock death subgroups increased, reaching the peak immediately after death. In the postmortem electric shock group, HIF-2α expression only increased immediately after death, but was lower than that of electric shock death group （P<0.05）. Compared with the control group, the expression of H-FABP in all subgroups of electric shock death group and postmortem electric shock group significantly decreased. The expression of H-FABP in all subgroups of electric shock death group was lower than that of the postmortem electric shock group （P<0.05）. Conclusion Electric shock can increase HIF-2α expression and decrease H-FABP expression in the myocardium, which may be of forensic significance for the determination of electric shock death and identification of antemortem and postmortem electric shock.
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Animals , Rats , Autopsy , Basic Helix-Loop-Helix Transcription Factors/metabolism , Fatty Acid Binding Protein 3/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Skin/ultrastructureABSTRACT
Shortage of donor kidney is a major problem in renal transplantation. Accurate evaluation of donor kidney function may reduce the organ rejection rate and save more patients with uremia. Compared with pathological examination, detection of circulating molecular markers is more convenient in clinical application. In this article, the research progress on the markers of kidney injury, such as serum creatinine, serum cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), mitochondrial DNA (mtDNA), kidney injury molecule-1(KIM-1) and interleukin -18 (IL-18), were briefly reviewed.
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Objective To investigate the role of fatty acid binding protein 4 (FABP4) in the apoptosis of mouse podocytes induced by hyperhomocysteinemia (HHcy). Methods Nine wild male C57BL/6J mice (Cbs+/+) and nine C57BL/6J male mice with cystathionine beta synthase gene knockout heterozygote (Cbs+/-) were used as the control group and HHcy model group, respectively. All mice were fed with 2% high methionine diet for 8 weeks to replicate the HHcy model. The ultrastructure of glomerular podocytes was observed by transmission electron microscopy. Glomerular podocytes were cultured in vitro and divided into blank control group (Control group) podocytes treated with Hcy concentration of 0 μmol•L-1 for 48 hours. The podocytes of homocysteine group (Hcy group) were treated with Hcy concentration of 80 μmol•L-1 for 48 hours. Podocytes were infected with GFP-labeled adenovirus (Ad-GFP group) and FABP4 overexpression adenovirus (Ad-FABP4 group), respectively. Podocytes were treated with Hcy and FABP4 adenovirus, named as Hcy+Ad-FABP4 group. The expression of FABP4 was detected by qRT-PCR and Western blot. The changes of apoptosis-related proteins Bax, Bcl-2 and Caspase-12 were analyzed by Western blot. The apoptosis rate of cells was measured by flow cytometry. Results Compared with the control group, the podocyte injury was aggravated and accompanied by the increasing number of apoptotic cells in the kidney tissues of model group mice. At the same time, the expression of FABP4 mRNA (3.20±0.42) and protein (4.98±1.12) in model group were higher than those in control group (2.09±0.13, 3.04±0.11)(P0.05); the mRNA expression levels (4.59±0.28) and protein expression (10.07±0.82) of FABP4 in Ad-FABP4 group were higher than those in Ad-GFP group (P<0.05). Bax/Bcl-2 value (3.15±0.65) and Caspase-12 protein expression (4.30±0.89) in Hcy group were higher than those in control group (2.19±0.10, 3.19±0.47) (P<0.05). The Bax/Bcl-2 values (5.42±0.55) and Caspase-12 protein expression (7.87±1.27) in the Hcy+Ad-FABP4 group were significantly higher than those in the Hcy+Ad-GFP group (3.19±0.47, 4.34±0.64) (P<0.05). FABP4 plays an important role in the apoptosis of mouse podocytes induced by HHcy. Flow cytometry analysis showed that the total apoptotic rate of Hcy group was (10.85±1.25) higher than that of control group (3.77±0.12) (P<0.05). Hcy + Ad-FABP4 group (15.72±1.60) was higher than that of Hcy+Ad-GFP group (11.22±0.43) (P< 0.05). Conclusion FABP4 promotes the apoptosis of podocytes in mice treated with HHcy.
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Objective To investigate the clinical values of the leukocyte count,D-dimer,histidine decarboxylase (HDC) and intestinal fatty acid binding protein (I-FABP) for diagnosing acute intestinal obstruction.Methods Sixty patients who treated in China-Japan Union Hospital of Jilin University from January 2017 to January 2018 were collected prospectively,and were divided into strangulated intestinal obstruction (STR-IO) group (n =20),simple intestinal obstruction (SIM-IO) group (n =20) and peritonitis group (n =20).Twenty healthy volunteers were collected as control group.Automatic blood cell analyzer was used to detecting the leukocyte count.The concentration of plasma D-dimer was detected by immune turbidimetry method.The concentration of serum HDC and I-FABP were measured by enzyme linked immunosorbent assay (ELISA) method.Compared the above indicators of four groups of samples.The measurement data are expressed as mean ± standard deviation (Mean ± SD).Tamhane's T2 and Dunnett's T3 methods were used to comparison between groups.Estimation of receiver operating characteristic curve(ROC) and area under curve (AUC) used logistic regressive model.Results The leukocyte count in control group,SIM-IO group,peritonitis group,and STR-IO group were (6.97 ± 1.68) × 109/L,(8.24 ± 2.78) × 109/L,(11.33 ±4.75) × 109/L,and(12.53 ± 5.96) × 109/L respectively.STR-IO group and peritonitis group were significantly higher than those of control group(F =12.74,P =0.01),but there was no significant difference between SIM-IO group and control group(P ＞ 0.05).The concentration of plasma D-dimer in control group,SIM-IO group,peritonitis group,and STR-IO group were (0.44± 0.30) μg/ml,(1.17 ± 0.67) μg/ml,(1.20 ± 0.72) μg/ml,and (1.67 ± 0.67) μg/ml respectively.The concentration of D-dimer in STR-IO group was significantly higher than those of control group (F =57.08,P =0.00),and there was no significant difference among other group (P ＞ 0.05).The concentration of serum HDC in control group,SIM-IO group,peritonitis group,and STR-IO group were (5.51 ±4.30) ng/ml,(14.33 ± 3.71) ng/ml,(11.53 ± 4.67) ng/ml,and (35.65 ± 21.15) ng/ml respectively.The concentration of HDC in STR-IO group was significantly higher than those of other three groups (F =39.03,P =0.00).The concentration of serum I-FABP in control group,SIM-IO group,peritonitis group,and STR-IO group were (0.20 ± 0.06) ng/m],(0.31 ± 0.17) ng/ml,(0.22 ±0.03)ng/ml,and (0.81 ±0.56) ng/ml respectively.The concentration of I-FABP in STR-IO group was significantly higher than those of other three groups (F =23.07,P =0.01).The AUC of HDC,I-FABP,D-dimer,and leukocyte count were 0.998,0.868,0.730,and 0.704 respactively.Conclusion Leukocyte count,D-dimer,and HDC or I-FABP combined detection may be a more effective index for diagnosing acute intestinal obstruction.
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Objective To study the changes and significance of serum intestinal fatty acid binding protein (IFABP) in children with traumatic brain injury(TBI) complicaled with acute gastrointestinal injury (AGI). Methods A total of 95 children suffering from TBI hospitalized in the PICU of the First Affiliated Hospital of Zhengzhou University from January 2017 to March 2018 were enrolled in the study. According to the modified Glasgow coma score combined with clinical classification criteria for acute closed head injury, the cases were devided into mild(43 cases),moderate (23 cases),and severe(29 cases). Children were gra-ded according to AGI (AGI Ⅰ42 cases,AGI Ⅱ 30 cases,AGI Ⅲ 13 cases,and AGI Ⅳ 10 cases). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group. Blood samples were collected at the time of admission and on the 3rd day after admission. Serum IFABP was detected by ELISA,and the differences of serum IFABP concentrations were compared among groups. The correlations between IFABP with TBI classification and AGI grade were analyzed. The receiver operating characteristic (ROC) curve was drawn,and the predictive values of IFABP for the diagnosis of children with TBI complicated with AGI were evaluated. Results On the day of admission,the serum levels of IFABP in mild,moderate and severe brain injury group were significantly higher than that in control group (all P <0. 01). And serum IFABP concentration gradually increased with the increase of brain injury (all P < 0. 01).Serum IFABP levels in children with AGI grade Ⅰto Ⅳ were significantly higher than those in control group (all P < 0. 01). The levels of serum IFABP also increased with the increase of AGI level (all P < 0. 01). The concentration of serum IFABP was positively correlated with the grade of TBI and AGI (rs = 0. 82,P < 0. 01;rs = 0. 70,P < 0. 01). In each group,the levels of serum IFABP on the 3rd day after admission were lower than those on admission (all P < 0. 01). The ROC curve analysis showed that serum IFABP was of high diag-nostic value in children with TBI complicated with AGI,and the area under the ROC curve was 0. 88. When the cutoff value of IFABP was 431. 36 ng/ L,the sensitivity and specificity were 71. 61％ and 90. 00％ ,re-spectively. Conclusion Serum IFABP can be used as a sensitive indicator for the early diagnosis and disease assessment in children with TBI complicated with gastrointestinal dysfunction.
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Objective To investigate the early diagnostic value of intra-abdominal pressure (IAP) combined with intestinal fatty acid binding protein (IFABP) for patients with mechanical ventilation complicated with acute gastrointestinal injury (AGI).Methods From August 2015 to December 2015,1 19 patients with mechanical ventilation were admitted to ICU in our hospital,with 78 cases of AGI patients and 41 cases of non-AGI patients.Multiple physiological indexes and laboratory indexes of the two groups were recorded and compared.Results There was no statistical difference in sex,age,APACHE Ⅱ score,BMI index,Lac and mean arterial pressure (MAP) between the two groups (P ＞0.05);the OR values of mechanical ventilation time,oxygenation index,end-expiratory positive pressure (PEEP),CIT,IFABP and IAP were more than 1,so these indicators were all risk factors for AGI in patients with mechanical ventilation.The area under the curve of IAP,IFABP,mechanical ventilation and PEEP were more than 0.5,indicating that these indicators have a certain predictive value for AGI patients with mechanical ventilation.The sensitivity and specificity of IAP were 95％ and 80％ respectively,and the sensitivity and specificity of IFABP were 87.5％ and 50％,respectively.IAP was correlated with IFABP (r =0.621,P =0.031).Conclusions Mechanical ventilation time,oxygenation index,PEEP,CIT,IFABP,and IAP are risk factors for AGI patients with mechanical ventilation.IAP,IFABP,mechanical ventilation time and PEEP have a certain predictive value for AGI patients with mechanical ventilation.The diagnostic value of IAP and IFABP is high,and the two are closely related.Combined application can provide a certain objective basis for clinical AGI diagnosis.
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Objective To observe the effects of Lianggesan on serum citrulline and intestinal fatty acid binding protein (IFABP) levels in patients with mechanical ventilation and acute gastrointestinal injury (AGI). Methods Eighty patients with mechanical ventilation and AGI admitted to Tianjin First Center Hospital from May to December 2017 were divided into a conventional treatment group and a traditional Chinese medicine (TCM) treatment group according to different treatment methods, 40 cases in each group; 10 patients with mechanical ventilation but without AGI were selected as a control group. All patients were given invasive mechanical ventilation after admission, and the gastrointestinal tract intervention was carried out according to AGI grading treatment process; Lianggesan (compositions:forsythia suspensa 30 g, scutellaria 10 g, gardenia 10 g, bamboo leaf 10 g, rhubarb 10 g, mint 6 g, mirabilite 6 g, licorice 15 g) was added to the TCM treatment group on the basis of the conventional treatment. The above TCM drug used was a single Chinese medicine granule produced by Jiangyin Tianjiang Pharmaceutical Co., Ltd. Each single Chinese herbal granule was proportionally poured into 200 mL boiling water at 80-100 ℃, 100 mL each time, twice daily nasal feeding for one week. The changes of serum citrulline and IFABP levels were observed before and 1, 3, 5 and 7 days after treatment in the three groups. Results Before treatment, serum citrulline levels in the conventional treatment group and the TCM treatment group were significantly lower than those in the control group (μmol/L: 19.84±4.74, 20.84±4.65 vs. 28.89±2.18, both P < 0.05), and IFABP levels were significantly higher than those in the control group (ng/L:571.89±42.89, 552.49±44.78 vs. 155.68±22.95, both P < 0.05), there were no significant differences between the conventional treatment group and the TCM treatment group (P > 0.05); with the extension of treatment time, the levels of citrulline in the conventional and TCM treatment groups were decreased first and then increased gradually, reaching the valley value on the first day of treatment [the two groups were (16.12±4.44), (18.49±4.59) μmol/L] respectively, and then increased gradually, reaching the peak value on the 7th day of treatment, the increased range of citrulline in the TCM treatment group was more obvious than that in the conventional treatment group (μmol/L: 26.77±4.18 vs. 22.75±3.07, P < 0.05), and the treatment lasted for 5 days, and 7 days, the level of citrulline in the TCM treatment group was close to that in the control group; the IFABP levels in the conventional treatment group and the TCM treatment group were increased first and then decreased gradually, reaching the peak value on the first day of treatment [the two groups were (654.23±63.24), (630.32±49.11) ng/L] respectively, and then decreased gradually, reaching the trough value on the 7th day of treatment, the degree of decrease in the TCM treatment group was more obvious than that in the conventional treatment group (ng/L: 262.21±30.89 vs. 375.43±44.43, P < 0.05), but the level of IFABP in the TCM treatment group was still significantly higher than that in the control group (ng/L: 262.21±30.89 vs. 158.95±29.34, P < 0.05). Conclusion Lianggesan can elevate the serum citrulline level, reduce the serum IFABP level, and effectively improve the intestinal function of patients with mechanical ventilation and AGI.
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Objective To observe the damage of various organs of rats with exertional heatstroke (EHS), and to investigate the protective effect of oral rehydration salts Ⅲ (ORSⅢ) on multi-organ function in rats with EHS. Methods Fifty-one male Sprague-Dawley (SD) rats were randomly divided into four groups by random digit table: normal control group (n = 13), EHS group (n = 13), EHS+water group (n = 12), and EHS+ORSⅢ group (n = 13). All rats in the EHS groups received adaptive training for 7 days before the experiment. On the 8th day, the rats of EHS+water and EHS+ORSⅢ groups were orally given 20 mL/kg water or ORSⅢ 30 minutes before the experiment. No pretreatment was performed in the EHS group. EHS model was reproduced by forcing rats to run under hot environment. The rats which refused to exercise and which core temperature > 40.5 ℃ were considered as the onset of EHS. The rats in the normal control group were exposed to room temperature (25±2) ℃ and humidity (50±5)% without any treatment. Six hours later, blood of inferior vena cava was collected, and the levels of serum MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (SCr), blood urea nitrogen (BUN), serum potassium, serum sodium and serum chloride were determined by automatic chemical analyzer. Serum intestinal fatty acid-binding protein (I-FABP) was determined by enzyme linked immunosorbent assay (ELISA). Results The levels of LDH, ALT, AST, BUN, serum sodium and serum chloride in the EHS group were significantly higher than those in the normal control group [LDH (U/L): 1 220±427 vs. 837±485, ALT (U/L): 138 (97, 164) vs. 37 (33, 42), AST (U/L): 409 (380, 566) vs. 86 (78, 104), BUN (mmol/L): 11.7 (9.6, 13.2) vs. 5.9 (5.5, 6.1), serum sodium (mmol/L): 148.0 (143.5, 154.5) vs. 139.0 (138.0, 140.5), serum chloride (mmol/L): 100.9±2.3 vs. 97.3±1.4, all P < 0.05], but no significant difference in CK-MB, SCr or serum potassium could be found [CK-MB (U/L): 1 280±373 vs. 1 379±480, SCr (μmol/L): 38.2±7.5 vs. 35.5±6.3, serum potassium (mmol/L): 5.5 (4.4, 6.2) vs. 4.7 (4.4, 4.9), all P > 0.05]. In the EHS+ORSⅢ group, only serum potassium level was significantly lower than that in the EHS group [mmol/L: 4.0 (3.7, 4.4) vs. 5.5 (4.4, 6.2), P < 0.01], while no significant difference in other parameters was found between the EHS+ORSⅢ group and the EHS group as well as the EHS+water group. Serum I-FABP level in the EHS group was significantly higher than that in the normal control group [μg/L: 36.90 (29.10, 45.00) vs. 11.39 (0.31, 20.80), P < 0.01]. Serum I-FABP level in the EHS+water and EHS+ORSⅢ groups were notably lower than that in the EHS group [μg/L:24.19 (20.00, 28.36), 0.31 (0.31, 5.58) vs. 36.90 (29.10, 45.00), both P < 0.01], additionally, I-FABP level was much lower in the EHS+ORSⅢ group (P < 0.01). Conclusions EHS could lead to liver, intestinal barrier dysfunction and electrolyte disturbance. Pre-treatment of ORSⅢ could alleviate the intestinal dysfunction and electrolyte disorder caused by EHS in rats. It can lower the serum potassium to some extent. However, ORSⅢ failed to protect liver from EHS.
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Objective To investigate the changes and clinical significances of intestinal fatty acid binding protein (I-FABP) and D-lactic acid levels in early intestinal injury of patients with sepsis and septic shock. Methods A prospective observational study was conducted. Thirty septic patients (septic group) and 30 septic shock patients (septic shock group) were admitted to the intensive care unit (ICU) of General Hospital of Ningxia Medical University from August 2018 to December 2018, and 20 healthy adults were served as healthy control group. Serum samples were collected within 24 hours after ICU admission in septic shock and septic groups, and in healthy control group during physical examination. The serum I-FABP, D-lactic acid, endotoxin, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and lactic acid (Lac) were determined. Gender and age of all subjects, and basic diseases, the main area of infection and acute physiology and chronic health evaluationⅡ(APACHEⅡ) scores within 24 hours after ICU admission of all patients were recorded. At the same time, the survival of the patients was followed up for 28 days. Spearman correlation analysis was used to analyze the correlation between serum I-FABP, D-lactic acid and other parameters. Risk factors of death in patients with sepsis and septic shock were screened by multivariate Logistic regression analysis of bicategorized variables. Results There was no significant difference in gender or age among the groups, as well as in the proportion of basic diseases, celiac infection or non-celiac infection between the sepsis group and the septic shock group, indicating that the general clinical baseline data among the groups were comparable. Serum levels of I-FABP and D-lactic acid in the sepsis group and the septic shock group were significantly higher than those in the healthy control group [I-FABP (μg/L): 27.46 (22.52, 34.39), 36.95 (29.82, 44.24) vs. 17.93 (14.65, 22.11), D-lactic acid (mg/L): 15.32 (9.84, 38.62), 27.95 (10.01, 47.69) vs. 9.38 (8.81, 14.48), all P < 0.01]. The serum level of I-FABP in the septic shock group was significantly higher than that in the sepsis group (P < 0.05), but the difference in serum D-lactic acid level between the two groups was not statistically significant (P > 0.05). Serum I-FABP level in the celiac infection group (n = 40) was significantly higher than that in the non-celiac infection group [n = 20; μg/L: 34.76 (27.46, 43.90) vs. 25.71 (20.55, 37.77), P < 0.01], but the difference in serum D-lactic acid level was not statistically significant [mg/L: 25.13 (9.83, 40.55) vs. 30.36 (10.17, 50.00), P > 0.05]. There was no significant difference in serum I-FABP or D-lactic acid levels between the survival group (n = 34) and the death group [n = 26; I-FABP (μg/L): 33.39 (25.20, 39.50) vs. 29.26 (22.50, 43.81), D-lactic acid (mg/L): 14.83 (9.71, 38.45) vs. 33.90 (11.93, 45.34), both P > 0.05]. Correlation analysis between serum I-FABP, D-lactic acid level and endotoxin, inflammatory factors, Lac and APACHEⅡ score in septic and septic shock patients showed that only D-lactic acid was significantly positively correlated with TNF-α and Lac (r values were 0.455 and 0.406, respectively, both P < 0.01), while I-FABP was not correlated with endotoxin, inflammatory factors, Lac or APACHEⅡscore. Multivariable Logistic regression analysis showed the APACHEⅡ score was an independent risk factor to affect the prognosis (death for 28 days) of septic and septic shock patients [odds ratio (OR) = 1.248, 95% confidence interval (95%CI) = 1.091-1.427, P = 0.001], while I-FABP, D-lactic acid, endotoxin, hs-CRP, TNF-α, IL-6, and Lac had no impact on 28-day prognosis of patients. Conclusion Serum I-FABP and D-lactic acid levels can evaluate early intestinal injury in patients with sepsis and septic shock, but neither of them is related to the prognosis of patients.