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Objective To assess the value of acute gastrointestinal injury(AGI)and intestinal fatty acid-binding protein(I-FABP)in the prognosis of liver cirrhotic patients with sepsis.Methods Clinical data of 84 liver cirrhosis patients with sepsis who were admitted to the intensive care unit(ICU)of a hospital from September 2020 to March 2023 were analyzed retrospectively,and 41 patients with decompensated liver cirrhosis during the same period were selected as the control group.Serum I-FABP level in patients was determined with enzyme-linked immunosorbent assay(ELISA).Scores of the model of end-stage liver disease(MELD)and sequential organ failure assessment(SOFA)were calculated.AGI was evaluated based on medical records.30-day and 90-day survival was observed.Correlation among variables was analyzed by Spearman correlation.Risk factors for death in patients with liver cir-rhosis and sepsis was determined by multivariate Cox regression analysis.The optimal cut-off value was determined by receiver operating characteristic(ROC)curve,and the diagnostic efficacy was compared through the area under the ROC curve(AUC).Results Both AGI grading and I-FABP level in liver cirrhosis patients with sepsis were higher than those in the control group(both P＜0.05).I-FABP level was correlated with procalcitonin(PCT),MELD,and SOFA scores in patients with liver cirrhosis and sepsis(all P＜0.05).AGI grading was positively cor-related with SOFA score(P=0.038).The 30-day and 90-day mortality of patients in the liver cirrhosis with sepsis group were 25.0％(n=21)and 35.7％(n=30),respectively.Multivariate Cox regression analysis showed that baseline I-FABP and SOFA scores were independently correlated with 30-day and 90-day survival,and the I-FABP quartile showed good prognostic differentiation efficacy.ROC curve showed that I-FABP could significantly improve the predictive effect of SOFA score on the prognosis of patients.Conclusion AGI grading and I-FABP level in liver cirrhosis patients with sepsis are elevated significantly.Serum I-FABP is associated with the prognosis of patient and can improve the predictive efficacy of SOFA score for survival.
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Objective To investigate the correlation between angiopoietin-2(Ang-2)and intestinal fatty acid binding protein(I-FABP)levels and the prognosis of acute myocardial infarction(AMI)with cardiac shock(CS).Methods A total of 198 patients with AMI admitted to Huzhou Central Hospital from July 2017 to July 2019 were selected as study objects,and were divided into CS group(n=93)and non-CS group(n=105)according to whether CS occurred during the hospital period,and 65 normal volunteers admitted for physical examination during the same period were included in control group.Patients in CS group were divided into survival group(n=50)and death group(n=43)according to their survival at 28 days.Serum Ang-2 and I-FABP levels of all subjects were detected,and Cox regression analysis was used to analyze the factors affecting the poor prognosis of AMI with CS.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of Ang-2 and I-FABP in AMI with CS.Results Serum Ang-2 and I-FABP levels in CS group were significantly higher than those in non-CS group and control group(P<0.05),and serum Ang-2 and I-FABP levels in non-CS group were significantly higher than those in control group(P<0.05).Serum Ang-2,I-FABP levels and proportion of diabetes in death group were significantly higher than those in survival group(P<0.05).Cox regression analysis showed that diabetes,Ang-2 and I-FABP levels were independent factors affecting the prognosis of AMI with CS(P<0.05).ROC curve showed that the area under the curve of Ang-2 and I-FABP combined to predict the prognosis of AMI with CS was 0.819,sensitivity was 81.4%,specificity was 80.0%.Conclusion Serum Ang-2 and I-FABP levels were elevated in patients with AMI with CS,which were potential biological indicators to predict the prognosis of patients.
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Objective The aim of this study was to screen and verify the proteins interacting with Vimentin,investigate the regulatory relationship between FABP5 and candidate proteins,and further explore the mechanism of FABP5 in hepatocellular carcinoma.Methods Immunoprecipitation combined with tandem mass spectrometry(IP-MS)was used to screen the proteins that bind to FABP5.The binding relationship between FABP5 and candi-date interacting proteins was verified from the exogenous and endogenous levels by Co-immune precipitation assay(Co-IP).RT-qPCR,Western blot and immunofluorescence were used to observe the effect of knockdown FABP5 on the transcription and translation of Vimentin in HCC cells.The effect of overexpressing FABP5 on the cytoskeleton of HCC cell was observed by phalloidin staining.Results 336 potential target proteins that bind to FABP5 were identi-fied through IP-MS.Based on literature,five candidate proteins related to tumors were selected,namely PRDX1,PRSS3,PKM,HSP90AA1,and Vimentin.The binding relationship between FABP5 and Vimentin protein was con-firmed through both exogenous and endogenous Co-IP.Knockdown FABP5 has no significant effect on the expression of Vimentin mRNA,but it can inhibit the expression of Vimentin protein,and overexpression of FABP5 can affect the cytoskeleton of HCC cell.Conclusions FABP5 promotes the migration and invasion of HCC cells by the regula-tion of Vimentin and the influence of cytoskeletal remodeling,and thus it is expected to be a potential target for anti-HCC and provide new ideas for the treatment of HCC.
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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 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 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 evaluate whether early enteral nutrition could benefit patients with different degrees of shock by dynamic changes of intestinal biomarkers intestinal fatty acid-binding protein (I-FABP) and citrulline.Methods:(1) From February 2021 to February 2023, 133 target patients in the Intensive Care Unit of Suzhou Hospital Affiliated to Nanjing Medical University were enrolled. The observation period was 7 days after admission, and intestinal biomarkers were monitored three times: 24 hours after admission (D1), the third day after admission (D3), and the seventh day after admission (D7). (2) The enrolled patients were divided into two groups according to the dose of norepinephrine received within 48 hours after admission: safe dose group [receiving norepinephrine < 0.3 μg/(kg·min)] and hazardous dose group [receiving norepinephrine ≥0.3 μg/(kg·min)]. The safe dose group was given early enteral nutrition according to the guidelines, and the dangerous dose group was randomly (random number) given early enteral nutrition (EEN) and delayed enteral nutrition (DEN).(4)The dynamic changes of intestinal fatty acid binding protein and citrulline in three groups were observed; The differences of intestinal biomarkers at different time points of dangerous dose of EEN/DEN were compared. The survival time of EEN/DEN group within 28 days was recorded, and Kaplan-Meier survival curve was drawn. Univariate and multivariate regression analyses of 28-day mortality were performed for the included population.Results:(1) The baseline data, APACHEⅡ score, arterial blood lactic acid, AGI grade, feeding interruption, total feeding time within 7 days, and 28-day survival number were statistically different between safe dose EEN group and hazardous dose EEN group ( P < 0.05). Compared the baseline data of the dangerous dose EEN group and the dangerous dose DEN group, only the number of feeding interruptions was statistically different ( P < 0.05). (2) The trend of change in the safe dose EEN group was the same as that in the dangerous dose DEN group: I-FABP decreased significantly from D3 to D7 ( P < 0.05); Citrulline decreased from D1 to D3, but increased from D3 to D7 ( P < 0.05). In dangerous dose EEN group, I-FABP had no significant change during the monitoring period ( P > 0.05). Citrulline decreased significantly from D1 to D3 ( P < 0.05). The EEN/DEN ratio at dangerous dose was significantly different only for D7-I-FABP ( P < 0.05). Compared with the survival curve of EEN/DEN at risk dose, DEN could improve the early survival rate of critically ill patients at risk dose (Breslow test P = 0.0447). (4) Age( OR=1.069,95% CI: 1.002-1.140, P=0.044) was independent risk factor for 28-day death . BMI ( OR= 0.772, 95% CI: 0.604-0.987, P=0.039), no feeding interruption ( OR=0.044,95% CI: 0.004-0.455, P=0.009), total feeding time within 7 days ( OR=0.959, 95% CI: 0.923-0.997, P=0.036) were the protective factors. Conclusions:EEN at the safe dose and DEN at the dangerous dose can effectively reverse the necrosis of enterocyte and promote the recovery of enterocyte function. EEN is not a clear risk factor for death at 28 days, but it not only increases the incidence of feeding interruption, but also do not conduct the recovery of intestinal cell function from the perspective of intestinal biomarkers.
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Objective To investigate the relationship between serum fatty acid binding protein(FABP)1,FABP2 and diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM)and its diagnostic value.Methods A total of 170 patients with T2DM diagnosed and treated in this hospital from January 2020 to December 2022 were selected as the research objects.According to urinary albumin to creatinine ratio(UACR),they were divided into non-DKD group(UACR<30 mg/g,72 cases)and DKD group(UACR≥30 mg/g,98 cases).A total of 60 healthy people in the same hospital during the same period were selected as the control group.Pearson correlation analysis was used to analyze the correlation between serum FABP1,FABP2 and renal function related indicators.Multivariate Logistic regression was used to analyze the influencing fac-tors of DKD.Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of serum FABP1 and FABP2 for DKD.Results The DKD group had significantly higher serum levels of FABP1 and FABP2 than the non-DKD group and the control group(P<0.05),and the non-DKD group had significantly higher serum levels of FABP1 and FABP2 than the control group(P<0.05).Compared with the non-DKD group,the DKD group had a significantly lower eGFR and significantly higher UACR,serum creatinine,blood urea nitrogen,and serum uric acid levels(P<0.05).Serum FABP1 and FABP2 levels were positively correla-ted with UACR,serum creatinine,blood urea nitrogen,and negatively correlated with eGFR(P<0.05).In-creased serum FABP1 and FABP2 levels were independent risk factors for DKD.The serum FABP1,FABP2 joint detection diagnosis efficiency was better than that of serum FABP1,FABP2 detection alone(Z=4.712,4.363,P=0.001,0.002).Conclusion The serum levels of FABP1 and FABP2 are increased in patients with DKD,and they are related to the degree of renal function damage,which are independent risk factors for the occurrence of DKD in patients with T2DM.The combined detection of FABP1 and FABP2 has a high diagnos-tic efficiency for the occurrence of DKD in patients with T2DM.
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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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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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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 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 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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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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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 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
Fatty acid binding protein 7 (FABP7) is a small molecular cytoplasmic protein. As a cellular fatty acid chaperone, it binds specifically to ligands such as DHA and is widely involved in physiological and pathological processes. During brain development, FABP7 is heavily expressed in neural stem cells, astrocytes and oligodendrocyte precursor cells, which plays a key role in regulating the pathology process of the central nervous system diseases. This article reviews the structure, expression and function of FABP7 and its related research progress in central nervous system disease.
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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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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.