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.

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.

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

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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.

Binding of naturally occurring hydroxycinnamic acids to bovine serum albumin

Hydroxycinnamic acids (HCAs) possess numer- ous biological effects including antioxidant, antiallergic, antimicrobial, and immunomodulatory activities and due to these properties are widely used in folk medicine. Nevertheless, they can interact with protein molecules and cause some structural and functional changes. The possib- ility of HCAs binding to bovine serum albumin (BSA) under physiological conditions was inve- stigated by the UV-VIS absorption spectroscopy and fluorescence quenching method. Apart from rosmarinic acid, all tested HCAs quenched tryptophan fluorescence of BSA in the studied range of concentrations (0-20 μM) mainly by static quenching mechanism (formation of non- fluorescent HCA-BSA complexes). The binding constants, number of binding sites and free energy changes were determined. The binding affinities of HCAs were ranked in the order: chlorogenic acid > sinapic acid ≥ caffeic acid > ferulic acid > o-coumaric acid > p-coumaric acid ≥ m-coumaric acid, which was confirmed by spectral overlaps of BSA emission spectrum with absorption spectrum of HCA. All free energy changes possessed negative sign indicating the spontaneity of HCA-BSA interaction.

Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen,ketoprofen and etodolac binding with HSA

The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin （HSA） was investigated using indirect chiral high performance liquid chromatography （HPLC） and ultrafiltration techniques. S-（-）-1-（1-naphthyl）- ethylamine （S-NEA） was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for the separation and assay of the three pairs of enantiomer. The method had good linear relationship over the investigated concentration range without interference. The average extraction efficiency was higher than 85% in different systems, and the intra-day and inter-day precisions were less than 15%. In serum albumin, the protein binding of etodolac enantiomers showed significant stereoselectivity that the affinity of S-enantiomer was stronger than R-enantiomer, and the stereoselectivity ratio reached 6.06; Flurbiprofen had only weak stereoselectivity in HSA, and ketoprofen had no stereoselectivity at all. Scatchard curves showed that all the three chiral drugs had two types of binding sites in HSA.

Histone Deacetylase Inhibitor SAHA Induces Expression of Fatty Acid-Binding Protein 4 and Inhibits Replication of Human Cytomegalovirus

Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity,SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus(HCMV) has not, however, been investigated. Here, we showed that the replication of HCMV was significantly suppressed by treatment with SAHA at concentrations that did not show appreciable cytotoxicity. SAHA reduced transcription and protein levels of HCMV immediate early genes, showing that SAHA acts at an early stage in the viral life-cycle. RNAsequencing data mining showed that numerous pathways and molecules were affected by SAHA. Interferon-mediated immunity was one of the most relevant pathways in the RNA-sequencing data, and we confirmed that SAHA inhibits HCMV-induced IFN-mediated immune responses using quantitative Real-time PCR(qRT-PCR). Fatty acid-binding protein 4(FABP4), which plays a role in lipid metabolism, was identified by RNA-sequencing. We found that FABP4 expression was reduced by HCMV infection but increased by treatment with SAHA. We then showed that knockdown of FABP4 partially rescued the effect of SAHA on HCMV replication. Our data suggest that FABP4 contributes to the inhibitory effect of SAHA on HCMV replication.

Effects of Yigan Tiaozhi Decoction on Serum NO, Endotoxin and RBP4 in Patients with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To explore the effects of Yigan Tiaozhi Decoction on serum nitric oxide(NO), endotoxin and retinol binding protein 4(RBP4) in patients with nonalcoholic fatty liver disease(NAFLD), and to provide evidence for clinical treatment of such patients. METHODS: A total of 92 patients with NAFLD admitted to Army General Hospital 263 Clinic from March 2013 to March 2017 were selected, and all patients were divided into the control group(n = 46) and the observation group(n = 46) according to the random number table method. The patients in the control group were given conventional treatment, and the patients in the observation group were treated with Yigan Tiaozhi Decoction on the basis of the control group. Liver function, blood lipid levels, serum NO, endotoxin, RBP4 levels and clinical efficacy were observed and compared between the 2 groups before and after treatment. RESULTS: Before treatment, there was no significant difference in serum alanine aminotransferase, glutamyltranspeptidase, aspartate aminotransferase, total cholesterol and triglyceride levels between the 2 groups(P > 0.05); after treatment, the serum levels of alanine aminotransferase, glutamyltranspeptidase, aspartate aminotransferase, total cholesterol and triglyceride in the observation group were lower than those in the control group, and the difference was statistically significant(P < 0.05); before treatment, there was no significant difference in serum NO, endotoxin and RBP4 levels between the 2 groups(P > 0.05); after treatment, the serum NO, endotoxin and RBP4 levels in the observation group were lower than those in the control group, and the difference was statistically significant(P < 0.05); the total effective rate of treatment in the observation group(89.13%) was significantly higher than that in the control group(76.09%), and the difference was statistically significant(P < 0.05). CONCLUSION: Yigan Tiaozhi Decoction is effective in NAFLD, which can reduce serum NO, endotoxin and RBP4 levels, improve liver function and reduce blood lipid levels.

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。

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。

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。

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。

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。

脂肪酸结合蛋白4在2型糖尿病肾病中的诊断价值

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清脂肪酸结合蛋白4(fatty acid-binding protein 4,FABP4)与糖尿病肾病(diabetic nephropathy,DN)的相关性及其作为DN早期诊断的应用价值。方法:纳入T2DM患者218例及健康体检者(对照组)20名,收集受试者的一般临床资料如身高、体质量、腰围、糖尿病病程等,计算BMI;收集血糖、糖化血红蛋白、空腹胰岛素、空腹C肽、肝肾功能、血脂等指标,计算稳态模型胰岛素抵抗指数(homeostasis model assessment-insulin resistance index,HOMA-IR)。采用ELISA测定血清FABP4水平;采用联合血肌酐(serum creatinine,Scr)和胱抑素C(cystatin C,Cys C)的慢性肾脏病流行病学协作方程式计算肾小球滤过率;测定尿白蛋白和肌酐水平,计算尿微量蛋白与肌酐比值(urinary albumin to creatinine ratio,UACR)。根据估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)水平将T2DM患者分为肾功能正常组(eGFR≥90 mL/min/1.73 m^(2))、轻度肾功能不全组(eGFR 60~<90 mL/min/1.73 m^(2))和中度肾功能不全组(eGFR 30~<60 mL/min/1.73 m^(2));根据UACR水平分为正常蛋白尿组(UACR<30 mg/g)、微量蛋白尿组(UACR 30~<300 mg/g)和大量蛋白尿组(UACR≥300 mg/g)。采用回归分析评估FABP4与eGFR、UACR严重程度的相关性。结果:(1)与对照组相比,T2DM患者的血清FABP4显著升高。(2)在根据eGFR分层的3个亚组中,随着eGFR的下降,血清FABP4水平显著增加(P<0.001)。但在UACR亚组中差异无统计学意义(P=0.382)。(3)Spearman相关分析显示FABP4与eGFR呈负相关(r=-0.203,P=0.001),与UACR无相关性(r=0.130,P=0.055)。(4)多元线性回归表明,FABP4与eGFR呈独立负相关(r=-0.211,P<0.001),与UACR无相关性(r=-0.047,P=0.534)。(5)ROC曲线显示FABP4诊断DN的最佳截断值为103.9μg/L,AUC为0.745(灵敏度51.2%,特异度92.7%)。结论:T2DM患者血清FABP4水平升高与DN发生发展相关,有可能作为DN早期诊断的生物标志物。

缺血修饰白蛋白与心脏型脂肪酸结合蛋白联合检测对不典型急性心肌梗死患者的早期诊断价值

目的:探讨缺血修饰白蛋白(IMA)与心脏型脂肪酸结合蛋白(H-FABP)联合检测对不典型急性心肌梗死(AMI)患者的早期诊断价值。方法:选择2021年1月—2022年6月湖南中医药高等专科学校附属第一医院收治的发病6 h内的176例可疑AMI患者作为研究对象,依照临床最终诊断结果将其分为有胸痛AMI组90例、无胸痛AMI组32例、非AMI组54例。选择同期在医院体检的30名健康者作为健康对照组。测定各组研究对象H-FABP、IMA、肌钙蛋白I(c TnI)及肌酸激酶同工酶(CK-MB)含量,计算H-FABP、IMA、H-FABP+IMA、cTnI、CK-MB对无胸痛AMI组患者的诊断性试验评价指标。结果:有胸痛AMI组及无胸痛AMI组患者IMA、H-FABP、cTnI、CK-MB水平均高于非AMI组患者及健康对照组研究对象,差异均有统计学意义(F=7.362、12.275、8.938、3.294、8.729、16.736、10.283、5.726,P<0.05);有胸痛AMI组患者与无胸痛AMI组患者IMA、H-FABP、cTnI、CK-MB水平比较,差异均无统计学意义(t=2.428、1.594、2.875、3.179,P>0.05)。IMA联合H-FABP检测诊断无胸痛AMI组患者的灵敏度、特异度、阳性预测值、阴性预测值、诊断效率均高于IMA、H-FABP、cTnI、CK-MB单独检测数据,差异均有统计学意义(χ^(2)=12.328、16.972、9.375、11.547,P<0.05)。结论:IMA与H-FABP联合检测对不典型AMI患者的早期诊断具有较高的临床价值。

miR-409-3p通过靶向脂肪酸结合蛋白4影响子宫内膜癌细胞转移的研究

目的用生物信息学方法预测脂肪酸结合蛋白4(FABP4)的上游调控miRNA,体外培养子宫内膜癌细胞Ishikawa,了解微小核糖核酸-409-3p(miR-409-3p)是否通过抑制FABP4的表达水平,进而影响Ishikawa细胞的生物学行为。方法实验分为control组、miR-409-3p mimics组、miR-409-3p inhibitor组、miR-409-3p NC组、FABP4-OE组及FABP4-shRNA组6组,采用实时定量聚合酶链式反应及蛋白质印迹法检测miR-409-3p及FABP4在Ishikawa中的表达情况;采用细胞增殖实验(CCK-8)、细胞侵袭及迁移实验(Transwell法)检测miR-409-3p与FABP4对Ishikawa细胞增殖、侵袭以及迁移能力的影响;用双荧光素酶报告基因实验在Ishikawa细胞中检测miR-409-3p对FABP4的调控作用。结果1)在Ishikawa细胞中下调FABP4的表达后,Ishikawa细胞的增殖、侵袭和迁移能力均显著降低(P<0.05);在Ishikawa细胞中上调FABP4的表达后,Ishikawa细胞的增殖、侵袭和迁移能力均显著升高(P<0.05)。2)在Ishikawa细胞中转染miR-409-3p mimics后,FABP4的表达水平以及Ishikawa细胞的增殖、侵袭和迁移能力均显著降低(P<0.05);而转染miR-409-3p inhibitor后,FABP4的表达水平以及Ishikawa细胞的增殖、侵袭和迁移能力均显著升高(P<0.05)。3)双荧光素酶报告基因结果显示,在Ishikawa细胞中miR-409-3p可靶向调控FABP4。结论高表达的FABP4促进Ishikawa细胞增殖、侵袭及迁移,miR-409-3p可通过下调FABP4的表达进而抑制Ishikawa细胞发生转移。