Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

Role of Heart-Type Fatty Acid Binding Protein in Early Detection of Acute Myocardial Infarction in Comparison with cTnI, CK-MB and Myoglobin

Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma levels of H-FABP were measured by sandwich ELISA in 93 patients with suspected AMI at admission within 6 h after onset of chest pain and 69 normal healthy subjects. The plasma concentrations of cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB) and myoglobin (Mb) were assayed at the same time by using corpuscle chemiluminescence for those patients. The patients were classified as AMI group (n=32) and non-AMI group (n=61) retrospectively. The diagnostic validity was evaluated in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve analysis. The results showed the cutoff value of H-FABP for AMI was 16.8 ng/ml, and its diagnostic sensitivity for AMI was 64.29 % within 3 h and 84.38 % within 6 h after onset of chest pain, and the diagnostic specificity for non-AMI was 100 % within 3 h and 91.8 % within 6 h. H-FABP had higher sensitivity than that of cTnI and CK-MB at all time points (P<0.05), whereas there was no significant difference in specificity among the four markers. But the area under the ROC curve of H-FABP was significantly greater than that of cTnI, CK-MB and Mb within 3 h. These results revealed that H-FABP possessed high diagnostic sensitivity and specificity for AMI in early stage, especially within 3 h after onset of persistent angina pectoris. In conclusion, H-FABP can be used as a sensitive marker for AMI in the early stage.

Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats

AIM: To investigate the effect of Platycodon grandi- florum extract (PGE) on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats. METHODS: PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03 ± 7.61 g were divided into four groups: the control groups that fed an experimental diet alone (C and H group) and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight (C + PGE and H + PGE group, respectively) for 7 wk. Plasma total cholesterol (TC) and triglycerol (TG) concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein (FABP) mRNA expression was analyzed by northern blot analysis. RESULTS: PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE signifi cantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue. CONCLUSION: PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat diet.From these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.

THE ASSOCIATION OF Ala54Thr VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN GENE WITH GENERAL AND REGIONAL ADIPOSE TISSUE DEPOTS

Objective. To ascertain the relationship between the Ala54Thr variation of FABP2 gene and general as well as regional adipose tissue depots. Subjects. 165 subjects, in which 86 were subjects with normal glucose tolerance (NGT) [age 54 45±9 80, male/female 1 05,body mass index (BMI)26 48±4 01] and 79 were subjects with non insulin dependent diabetes mellitus (NIDDM)(age 55 86±10 00,male/female 1 08,BMI 26 75±3 30). Design and measurements. An association study of FABP2 Ala54Thr variation detected by PCR/HhaI digestion with general and regional adipose tissue depots determined by BMI and magnetic resonance imaging [abdominal subcutaneous and visceral adipose tissue area (SA and VA) and femoral subcutaneous adipose tissue area (FA)]. Results. The geneotype and allele frequencies of FABP2 Ala54Thr variation in Chinese were quite close to the frequencies in American Caucasians and Pima Indians reported in the literature. Significant difference in genotype frequency distribution was observed between FA subgroups comparisons (FA≥75cm 2 versus FA<75cm 2 )in NIDDM subjects (X 2 =11 460,P=0 003),with significantly increased in Thr54 carrier[Thr54(+)]genotype frequency and Thr54 allele frequency in NIDDM subject with FA<75cm 2 (odd ratio for genotype was 4 62,X 2 =10 112,P=0 001;and for allele=2 36,X 2 =5 379,P=0 020).The FA in NIDDM Thr54(+)subgroup was significantly lower than that in subjects with NIDDM Thr54( )sugroup(61 19±21 51cm 2 versus 75 36±31 70cm 2 ,P=0 021). Stepwise regression analysis revealed that FABP2 Thr54 genotype variation was an independent factor contributing to the variation of FA in NIDDM(P=0 003). Conclusion. FABP2 is associated with regional adipose tissue depot.The decreased femoral subcutaneous adipose tissue depot in NIDDM subjects is related to FABP2 Thr54 variant.

Expression and Characterization of Human Heart Type Fatty Acid Binding Protein in Pichia Pastoris

H-FABP is regarded as a tissue-specific protein existing only in myocardial cells. It is released from the cardiac tissue and gets into the plasma when a heart attack occurs; the myocardial infarction is a good case in point. As a resuit, the detection of H-FABP will be an early and important biomarker for the disease concerned. The objective of the study is to prepare the recombinant H-FABP by aeukaryotic expression system, pichia, to produce the protein mimicking natural H-FABP, as an immunogen for the production of the specific antibody. A gene fragment encoding H-FABP was cloned in the expressing vector pPICZα, after sequencing. The recombinant plasmid was transformed into the competent cells of the X-33 strain by means of electroporation. The expression of the target peptide induced by methanol was screened by means of Western hlotting, with the available MAb（Clone 6B6）. Highly expressive engineer strains were obtained. The production of recombinant H-FABP under induction was about 0.7 g/L, with an Mr of 14.5 kDa and recognized by a commercially available MAb （Clone 6B6）. The recombinant vector was successfully constructed. Following this, H-FABP was expressed in X-33, and it would become the source of the preparation of specific antibodies, to develop diagnostic kits.

Correlation study of serum epithelial fatty acid binding protein with glucose and lipid metabolism and micro inflammatory reaction in obese children

Objective: To study the correlation of serum epithelial fatty acid binding protein (E-FABP) with glucose and lipid metabolism and micro inflammatory reaction in obese children. Methods: children diagnosed as simple obesity in endocrinology department of my hospital during June 2014 – August 2017 were selected as the obese group, and the health examination children were selected as the control group. The serum was collected and the levels of E-FABP, glucose and lipid metabolism and inflammatory cytokines were determined, peripheral blood was collected and the expression level of insulin signal molecules were measured. Results:serum E-FABP content of obese group was significantly higher than that in the control group;serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), Leptin, Chemerin, F-INS, tumor necrosis factor - α (TNF-α), interleukin -1β (IL-β), interleukin-6 (IL-6), soluble intercellular adhesion molecule -1 (sICAM-1) and monocyte chemoattractant protein 1 (MCP1) of obese group were significantly higher than thosein the control group and positively correlated with serum E-FABP content;serum high density lipoprotein cholesterol (HDL-C), lipoprotein (APN), and C1q/tumor necrosis factor-related proteins 12 (CTRP12), Omentin-1 and the expression intensity of insulin receptor substrate 1 (IRS1), IRS2, glucose transporter -4 (GLUT-4) in peripheral blood were significantly lower than those of the control group and negatively correlated with serum E-FABP content. Conclusion: the excessive secretion of E-FABP in obese children is closely related to the disorder of glucose and lipid metabolism and the activation of micro inflammatory reaction.

Sequencing of Intron 3 of Porcine Heart Fatty Acid-Binding Protein Gene

[ Objective] The aim of this paper is to provide the basic data for marker-assisted selection of pig breeding using porcine heart fatty acid- binding protein （H-FABP） gene. [Method] According to the related sequences of porcine H-FABP gene released in GenBank, specific primers were designed to amplify the intron 3 of porcine H-FABP gene. [ Result] The intron 3 of porcine H-FABP gene was amplified successfully. Its whole sequence was 1 350 bp in length and had been submitted to GenBank （Accession no. ： DQ 002993）. [Condusion] The study lays a theoretical foundation for determination of the major genes affecting intramuscular fat deposition.

Combined assessment of myocardial damage and electrical disturbance in chronic heart failure

AIM To investigate feasibility of combined assessment of biochemical and electrophysiological myocardial impairment markers risk-stratifying patients with chronic heart failure(CHF). METHODS Serum levels of heart-type fatty acid binding protein(H-FABP) as a marker of ongoing myocardial damage and QRS duration on electrocardiogram were measured at admission in 322 consecutive patients with CHF. A prolonged QRS duration was defined as 120 ms or longer. The cut-off value for H-FABP level(4.5 ng/mL) was determined from a previous study. Patients were prospectively followed during a median follow up period of 534 d. The primary endpoint was cardiac deaths and rehospitalization for worsening CHF.RESULTS There were 117 primary events, including 27 cardiac deaths and 90 rehospitalizations. Patients were stratified into four groups according to H-FABP level and QRS duration(≥ 120 ms). Multivariate analysis demonstrated that high H-FABP levels [hazard ratio(HR) = 1.745, P = 0.021] and QRS prolongation(HR1.612, P = 0.0258) were independent predictors of cardiac events. Kaplan-Meier analysis demonstrated that the combination of high H-FABP levels and QRS prolongation could be used to reliably stratify patients at high risk for cardiac events(log rank test P < 0.0001).CONCLUSION Combined assessment of myocardial damage and electrical disturbance can be used to risk-stratify patients with CHF.

The impact of codon 54 variation in intestinal fatty acid binding protein gene on the pathogenesis of diabetes mellitus in Chinese

Objective To investigate whether or not the intestinal fatty acid binding protein gene (FABP2) Ala54Thr variation is related to non insulin dependent diabetes mellitus (NIDDM), obesity, dyslipidemia and glucose stimulated insulin secretion (GSIS) in Chinese.Methods The FABP2 Ala54Thr variation was detected by PCR/HhaI digestion in 231 Chinese subjects (116 with normal glucose tolerance (NGT), 54 with impaired glucose tolerance (IGT) and 61 with NIDDM). Plasma glucose, insulin and C peptide levels before and after 75 g glucose load as well as fasting lipid profile were determined.Results (1) The Ala54 and Thr54 allele frequencies in Chinese were 0.71 and 0.29 respectively; (2) The FABP2 Ala54Thr variation was neither associated with fasting and post challenged plasma glucose levels nor with NIDDM; (3) This variation was neither associated with fasting lipid profile nor with obesity; (4) The IGT subjects with genotype Thr54(+) (Thr54 homozygotes and heterozygotes) had lower fasting, 2 hour and total C peptide levels and smaller AUC representing lesser C peptide secretion after glucose challenge than those with genotype Thr54( ) (Ala54 homozygotes) (P= 0.04 , 0.03, 0.01 and 0.01 respectively). The serum insulin levels changed in the same tendency.Conclusions The glucose stimulated insulin secretion (GSIS) reserve of islet beta cells is more limited in subjects with FABP2 Thr54(+) genotype than in those with FABP2 Thr54(-) genotype. It suggests that FABP2 codon 54 variation might contribute to the insufficient insulin secretion in the development of NIDDM in Chinese.

Preliminary study on plasma membrane fluidity of Psychrophilic Yeast Rhodotorula sp.NJ298 in low temperature

The ability of cell to modulate the fluidity of plasma membrane was crucial to the survival of microorganism at low temperature.Plasma membrane proteins,fatty acids and carotenoids profiles of Antarctic psychrophilc yeast Rhodotorula sp.NJ298 were investigated at-3 ℃,0 ℃ and 8 ℃.The results showed that plasma membrane protein content was greater at-3 ℃ than that at 8 ℃,and a unique membrane polypeptide composition with an apparent molecular mass of 94.7 kDa was newly synthesized with SDS-PAGE analysis;GC analysis showed that the main changes of fatty acids were the percentage of unsaturated fatty acids(C18:1 and C18:2) and shorter chain saturated fatty acid(C10:0) increased along with the decrease of the culture temperature from 8 ℃ to-3 ℃;HPLC analysis indicated that astaxanthin was the major functional carotenoids of the plasma membrane,percentage of which increased from 54.6±1.5% at 8 ℃ to 81.9±2.1% at-3 ℃.However the fluidity of plasma membrane which was determined by measuring fluorescence anisotropy was similar at-3 ℃,0 ℃ and 8 ℃.Hence these changes in plasma membrane’s characteristics were involved in the cellular cold-adaptation by which NJ298 could maintain normal plasma membrane fluidity at near-freezing temperature.

Specific protein-urea interactions

The mechanism of urea's action in protein denaturation remains largely unknown.To provide an experimental basis for molecular dynamics(MD)simulations on urea-protein interactions,we investigated the effect of urea on human intestinal fatty acid binding protein(hIFABP)by nuclear magnetic resonance(NMR).Hydrogen-deuterium exchange(HDX)rates at
2 M urea indicate that urea affects hIFABP in a residue-specific manner via direct urea-protein interactions and preferentially weakens hydrogen bonds between highly protected amides.Residue-specific effects of urea on NMR peak intensities and chemical shifts further support the presence of direct urea-protein interactions.Twodimensional(2D)water-rotating frame Overhauser enhancement(ROE)data shows one protein-bound water molecule in contact with Val66 and Trp82,one putative bound water molecule in interaction with Thr76 and E-F loop,and that urea at low concentrations cannot displace these protein-bound water molecules.Our urea-nuclear Overhauser effect(NOE)experiments using 15N-urea further show no tightly protein-bound urea molecules.Our results thus suggest specific,but weak or transient,urea-protein interactions,supporting the direct interaction model of urea denaturation.

Clinical significance of combined detection of EASI lead and serum H-FABP, IMA in the diagnosis of coronary heart disease patients with myocardial ischemia

Objective:To explore the significance of combined detection of EASI lead and serum H-FABP, IMA in the diagnosis of coronary heart disease patients with myocardial ischemia.Methods:The 106 patients with myocardial ischemia of coronary heart disease treated in our hospital from March 2016 to June 2018 were taken as observation group and 106 healthy adults who were examined in our hospital at the same time were defined as control group. The abnormal rate of electrocardiogram (ECG), serum heart-type fatty acid binding protein (H-FABP) and ischemic modified albumin (IMA) in them, the diagnostic efficacy of single and combined detection in diagnosing myocardial ischemia of coronary heart disease and the area under receiver operating characteristic (ROC) curve of different joint detection were compared. Results: The abnormal rate of ECG, serum H-FABP and IMA levels in the observation group were higher than the control group. The specificity of EASI lead, serum H-FABP and IMA in the diagnosis of coronary heart disease patients with myocardial ischemia was different, the diagnostic specificity of H-FABP was higher than that of EASI lead and serum IMA. TThe sensitivity and negative predictive value of different parallel combined detection in diagnosing coronary heart disease were different. The specificity of different series of combined detection in the diagnosis of coronary heart disease was different. The areas under ROC curve of EASI lead+ H-FABP, H-FABP +IMA and EASI lead+ H-FABP +IMA were 0.713, 0.782 and 0.914, respectively, and the areas under ROC curve of series of combined detection were 0.709, 0.724 and 0.883, respectively. The area under the ROC curve of EASI lead+H-FABP+IMA was higher than that of EASI lead+H-FABP and H-FABP+IMA.Conclusions: The combination of EASI lead and serum H-FABP and IMA is of great significance in the diagnosis of coronary heart patients with myocardial ischemia. Combined application in clinical work can be considered.

血清成纤维细胞生长因子21和脂肪酸结合蛋白4检测对急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗术后心力衰竭的预测价值

目的探究血清成纤维细胞生长因子21(FGF21)和脂肪酸结合蛋白4(FABP4)检测对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后心力衰竭的预测价值。方法选取2020年9月至2022年9月内蒙古医科大学附属医院接诊的113例STEMI患者为研究对象,依据PCI术后1年是否发生心力衰竭(心衰),将其分为心衰组(n=32)和非心衰组(n=81)。应用ELISA法测定血清FGF21、FABP4表达水平,比较两组血清FGF21、FABP4水平,多因素logistic回归分析影响STEMI患者PCI术后发生心力衰竭的相关因素,ROC曲线评估血清FGF21、FABP4水平对STEMI患者PCI术后心力衰竭发生的预测价值。结果心衰组心率次数、C反应蛋白(CRP)、心肌肌钙蛋白(cTnI)、N末端B型利钠肽原(BNP)、利尿剂使用比例均显著高于非心衰组,左心室射血分数(LVEF)显著低于非心衰组(P<0.05)。心衰组血清FGF21、FABP4表达水平均明显高于非心衰组[(228.37±33.07)ng/L比(185.68±25.52)ng/L、(34.26±5.51)ng/ml比(26.87±4.67)ng/ml,t=7.345、7.195,P<0.05]。血清FGF21(95%CI 1.371~8.191)、FABP4(95%CI 1.176~4.090)及发病到至导丝通过时间(95%CI 1.058~8.157)是影响STEMI患者PCI术后发生心力衰竭的危险因素(OR>1,P<0.05),LVEF(95%CI 0.473~0.913)是保护因素(OR<1,P<0.05)。血清FGF21、FABP4单独及二者联合预测STEMI患者PCI术后发生心力衰竭的曲线下面积(AUC)分别为0.828、0.856、0.934,二者联合优于单一(Z二者联合-FGF21=1.971、Z二者联合-FABP4=2.417,P=0.048、P=0.015)。结论STEMI患者PCI术后发生心力衰竭血清FGF21、FABP4水平均明显升高,二者联合对STEMI患者PCI术后发生心力衰竭的风险具有更高的预测价值。

H-FABP、NT-proBNP与急性心力衰竭患者容量负荷状态及预后的相关性

目的 研究心型脂肪酸结合蛋白(H-FABP)、氨基端脑钠肽前体(NT-proBNP)对急性心力衰竭患者容量负荷状态及预后的评估。方法 本研究为前瞻性研究,以2021年1月至2022年1月于安阳市人民医院急诊住院的老年急性心力衰竭患者83例作为研究组,另选取83例健康者作为对照组。根据相对容量平衡水平,将以上83例患者分为容量超负荷组和非容量超负荷组,对所有出院患者随访3个月,将发生死亡的患者归为死亡组,其余为生存组。比较研究组与对照组不同容量负荷、不同预后的H-FABP、NT-proBNP水平之间的差异,研究H-FABP、NT-proBNP与生存状况以及容量负荷状态的相关性。结果 研究组患者的H-FABP、NT-proBNP水平高于对照组(P<0.001);容量超负荷组患者的H-FABP、NT-proBNP水平高于非容量超负荷组(P<0.05);死亡组患者的H-FABP、NT-proBNP水平高于生存组(P<0.05)。通过相关性分析,患者的死亡以及容量超负荷与H-FABP、NT-proBNP呈现正相关(P<0.001)。结论 H-FABP、NT-proBNP与急性心力衰竭患者容量负荷状态及预后呈现相关性,有助于评估急性心力衰竭的严重程度,对预后不良患者起到积极的指导治疗作用。

2型糖尿病伴干眼症病人血清和泪液分泌型卷曲相关蛋白5、脂肪酸结合蛋白4水平与病情严重程度的相关性

目的分析分泌型卷曲相关蛋白5(SFRP-5)、脂肪酸结合蛋白4(FABP4)在2型糖尿病(T2DM)伴干眼症病人血清和泪液中的表达及其与病情严重程度的相关性。方法选取2020年12月至2021年12月唐山市眼科医院收治的T2DM病人145例,其中单纯T2DM病人84例168眼(T2DM组),伴干眼症病人61例122眼(T2DM伴干眼症组),另选取同期该院体检健康者50例100眼作为对照组。T2DM伴干眼症病人又分为轻度组(29例)、中度组(17例)、重度组(15例)。利用酶联免疫吸附法测定所有受试者血清和泪液中SFRP-5、FABP4水平;相关性分析采用Pearson法或Spearman法;logistic回归分析影响T2DM病人干眼症发生的因素。结果T2DM伴干眼症组、T2DM组血清和泪液SFRP-5水平均低于对照组(106.09±8.37、135.72±9.26比158.34±9.45,28.85±5.13、58.27±6.14比45.18±5.92),T2DM伴干眼症组低于T2DM组(P<0.05);T2DM伴干眼症组、T2DM组血清和泪液FABP4水平均高于对照组(70.63±6.59、58.27±6.14比45.18±5.92,15.91±3.76、10.28±3.58比7.72±3.29),T2DM伴干眼症组高于T2DM组(P<0.05)。重度组、中度组血清和泪液SFRP-5水平(68.29±7.15、95.54±8.34比131.82±9.02,12.83±4.62、24.72±5.49比39.56±5.18)、泪膜破裂时间(BUT)、泪液分泌试验(SIT)低于轻度组,重度组低于中度组(P<0.05);重度组、中度组血清和泪液FABP4水平(84.56±6.83、73.18±6.94比61.93±6.27,25.64±4.19、17.15±3.86比10.16±3.47)及眼表疾病指数量表(OSDI)积分高于轻度组,重度组高于中度组(P<0.05)。T2DM伴干眼症病人血清与泪液SFRP-5水平呈正相关,血清与泪液FABP4水平也呈正相关(P<0.05)。T2DM伴干眼症病人血清和泪液SFRP-5水平与OSDI积分均呈负相关,与BUT、SIT均呈正相关(P<0.05);血清和泪液FABP4水平与OSDI积分均呈正相关,与BUT、SIT均呈负相关(P<0.05)。血清和泪液SFRP-5水平是影响T2DM病人干眼症发生的独立保护因素,而血清和泪液FABP4水平是独立危险因素(P<0.05)。结论SFRP-5在T2DM伴干眼症病人血清和泪液中均低表达,FABP4均高表达,二者与病情严重程度密切相关。

脂肪酸结合蛋白5结合Vimentin蛋白在肝癌中的作用机制

目的 筛选和验证与脂肪酸结合蛋白5(FABP5)结合的互作蛋白,同时研究FABP5与候选蛋白的调控关系,进一步探讨FABP5在肝癌中的作用机制。方法 采用免疫沉淀联合串联质谱分析方法(IP-MS)筛选出与FABP5相互结合的蛋白;通过免疫共沉淀实验(Co-IP)从外源性和内源性层面验证FABP5与候选互作蛋白的结合关系;利用RT-qPCR、Western blot和免疫荧光法观察敲低FABP5对肝癌细胞中波形蛋白(Vimentin)转录和翻译水平的影响;通过鬼笔环肽染色实验观察过表达FABP5对肝癌细胞骨架的影响。结果 IP-MS鉴定出336个与FABP5相互结合的潜在靶蛋白,结合文献,挑选出5个与肿瘤相关的候选蛋白,分别为PRDX1、PRSS3、PKM、HSP90AA1和Vimentin蛋白。通过外源性和内源性Co-IP实验证实FABP5与Vimentin蛋白存在结合关系。敲低FABP5对肝癌细胞中Vimentin mRNA的表达没有显著作用,但可抑制Vimentin蛋白的表达,而过表达FABP5会影响肝癌细胞的骨架。结论 FABP5促进肝癌细胞的迁移和侵袭,其机制可能与FABP5结合调控Vimentin蛋白和影响细胞骨架重塑有关,有望成为抗肝癌的潜在靶点,为肝癌的治疗提供新的思路。

肠脂肪酸结合蛋白和D-乳酸在早期诊断嵌顿疝肠坏死中的应用研究

目的:探讨肠脂肪酸结合蛋白(I-FABP)和D-乳酸(D-LAC)早期诊断嵌顿疝肠坏死的价值。方法:选取36只SD大鼠,实验组(n=18)制作嵌顿疝动物模型,对照组(n=18)未制作。在术后30 min、2 h、4 h、6 h、8 h和12 h,采用ELISA检测两组血清D-LAC和I-FABP的水平;RT-qPCR鉴定嵌顿疝肠管组织中I-FABP的表达。通过嵌顿肠管大体标本、苏木素伊红(HE)染色和Chiu’s评分判定肠坏死情况。结果:与对照组相比,实验组在术后6 h时嵌顿肠管大体标本和HE染色呈典型肠绞窄表现,Chiu’s评分有统计学意义(P=0.001),血D-LAC明显升高(P=0.002);8 h时肠管逐渐向肠坏死过渡,血D-LAC进一步升高(P=0.012),血I-FABP也明显升高(P=0.001),并且肠组织中的I-FABP表达明显升高(P=0.002)。12 h时肠管呈现明显肠坏死特征、Chiu’s评分有统计学意义(P=0.001),血D-LAC和I-FABP均升至最高[(2019.60±16.17)μg/L vs(273.18±14.63)μg/L,P=0.001;(1210.94±5.96)μg/L vs(220.46±9.63)μg/L,P=0.001];肠管组织中的I-FABP表达最高[(8.20±0.60)μg/L vs(1.13±0.16)μg/L,P=0.001]。结论:嵌顿疝大鼠血清I-FABP和D-LAC水平升高,为早期诊断嵌顿疝肠管坏死的临床研究提供了依据。

多重标志物联合检测模型在诊断4a型急性心肌梗死中的应用

目的与单一标志物高敏肌钙蛋白T(cTnT)进行对比,初步探索多重心肌标志物[和肽素(copeptin)、cTnT和心脏型脂肪酸结合蛋白(HFABP)]联合检测模型在诊断4a型急性心肌梗死(AMI)中的应用价值。方法纳入2022年3月至12月期间在南京医科大学第一附属医院接受择期经皮冠状动脉介入治疗(PCI)且术后cTnT升高超过正常参考值上限(URL)第99百分位数的非AMI患者。根据《第四版心肌梗死通用定义》,按照术后是否出现4a型AMI将患者分为非4a型AMI组和4a型AMI组。采用化学发光免疫金纳米组装体免疫传感阵列(ciGold)测定AMI生物标志物浓度。通过受试者工作特征(ROC)曲线分析单一标志物和多重联合心肌标志物诊断模型的诊断性能,从ROC曲线获得敏感性和特异性,计算ROC曲线下面积(AUCROC)评估各自诊断价值。使用Kappa分析评估多重标志物联合检测模型与《第四版心肌梗死通用定义》诊断的一致性。结果共纳入65例患者,女性占23.1%。ROC曲线分析显示,多重联合心肌标志物诊断模型的特异性为96.5%,敏感性为92.3%,符合率为94.6%,阳性预测值为92.3%,阴性预测值为96.2%,AUCROC为0.979。cTnT模型的特异性为94.2%,敏感性为100%,符合率为95.7%,阳性预测值为100%,阴性预测值为94.9%,AUCROC为0.987。虽然多重标志物联合检测模型诊断敏感性较低(P=0.011),但具有更高的特异性(P=0.016)。两种诊断模型准确性的AUCROC差异性分析提示P>0.05,诊断准确性无明显统计学差异。Kappa分析结果表明,多重联合心肌标志物检测模型与《第四版心肌梗死通用定义》诊断4a型AMI具有高度一致性,Cohen′s Kappa系数为0.818。结论多重标志物联合检测模型与cTnT在诊断4a型AMI方面性能相近,诊断一致性高,但联合检测模型具有更高的特异性优势。

血清胎球蛋白A和脂肪酸结合蛋白4及微小RNA-31对妊娠期糖尿病妊娠结局的预测价值

目的探讨血清胎球蛋白A、脂肪酸结合蛋白4(FABP4)和微小RNA-31(miR-31)与妊娠期糖尿病(GDM)的关系及对妊娠结局的预测价值。方法选取新疆维吾尔自治区人民医院2022年1月至2023年3月收治的GDM患者120例作为观察组,同时选取健康孕妇120例作为对照组。检测2组血清胎球蛋白A、FABP4、miR-31水平,分析不同临床特征患者胎球蛋白A、FABP4、miR-31水平及其与胰岛素抵抗指数(HOMA-IR)相关性,以及预测不良妊娠结局的价值。结果观察组血清胎球蛋白A、FABP4、miR-31水平均高于对照组[(40±10)μg/L比(30±7)μg/L、(27.1±3.6)mg/L比(15.6±2.9)mg/L、(2.03±0.41)比(1.00±0.26)](均P<0.001)。观察组HOMA-IR≥5、发生不良妊娠结局患者胎球蛋白A、FABP4、miR-31水平均分别高于HOMA-IR<5、未发生不良妊娠结局患者(均P<0.05)。观察组患者血清胎球蛋白A、FABP4、miR-31均与HOMA-IR呈正相关(均P<0.001)。血清胎球蛋白A、FABP4、miR-31预测不良妊娠结局的受试者工作特征曲线下面积分别为0.733、0.831和0.824。结论GDM患者血清胎球蛋白A、FABP4、miR-31水平升高,与HOMA-IR呈正相关,在预测不良妊娠结局方面有一定应用价值。

2型糖尿病合并代谢综合征患者血清CTRP9、A-FABP水平变化及临床意义

目的研究2型糖尿病(T2DM)合并代谢综合征(MS)(T2DM~MS)患者血清补体C1q肿瘤坏死因子相关蛋白(CTRP9)、脂肪型脂肪酸结合蛋白(A-FABP)水平变化及临床意义。方法前瞻性选择2021年1月至2023年12月于广西医科大学第二附属医院治疗的90例T2DM患者纳入研究组,根据是否合并MS将其分为T2DM~MS组(n=71)、T2DM未合并MS组(n=19)。将同期于广西医科大学第二附属医院进行体检的90名健康者纳入对照组。检测并比较研究组与对照组、T2DM~MS组与T2DM未合并MS组的糖脂代谢指标[空腹血糖、高密度脂蛋白(HDL-C)、总胆固醇、低密度脂蛋白(LDL-C)、甘油三酯]及血清CTRP9、A-FABP水平。采用Pearson相关性分析CTRP9、A-FABP与各糖脂代谢指标的相关性;采用受试者操作特征(ROC)曲线评价CTRP9、A-FABP对T2DM~MS的诊断效能。结果研究组的空腹血糖、总胆固醇、LDL-C、甘油三酯及血清A-FABP水平分别为(9.37±0.95)mmol/L、(4.38±0.45)mmol/L、(2.83±0.29)mmol/L、(1.58±0.17)mmol/L、(15.48±1.72)ng/mL,均高于对照组,研究组HDL-C及血清CTRP9水平分别为(1.23±0.14)mmol/L、(8.38±0.85)ng/mL,均低于对照组,差异均有统计学意义(P<0.05)。T2DM~MS组空腹血糖、总胆固醇、LDL-C、甘油三酯及血清A-FABP水平分别为(10.26±1.32)mmol/L、(4.51±0.47)mmol/L、(3.15±0.33)mmol/L、(1.74±0.20)mmol/L、(18.21±2.06)ng/mL,均高于T2DM未合并MS组,T2DM~MS组HDL-C及血清CTRP9水平分别为(1.12±0.13)mmol/L、(7.26±0.75)ng/mL,均低于T2DM未合并MS组,差异均有统计学意义(P<0.05)。经Pearson相关分析,血清CTRP9水平与空腹血糖、总胆固醇、LDL-C、甘油三酯均呈负相关(r=-0.902、-0.780、-0.745、-0.753;均P<0.05),与HDL-C呈正相关(r=0.827,P<0.05);血清A-FABP水平与空腹血糖、总胆固醇、LDL-C、甘油三酯均呈正相关(r=0.843、0.812、0.839、0.722;均P<0.05),与HDL-C呈负相关(r=-0.768,P<0.05)。经ROC曲线分析,血清CTRP9联合A-FABP对T2DM~MS的诊断效能高于两者单独诊断。结论T2DM~MS患者血清CTRP9水平低表达,A-FABP水平高表达,血清CTRP9、A-FABP水平与糖脂代谢指标密切相关。血清CTRP9联合A-FABP可提高T2DM~MS的诊断效能,监测血清CTRP9、A-FABP水平有助于预测T2DM~MS的发生。