Regulation of Acyl-coenzyme A:Cholesterol Acyltransferase 2 Expression by Saturated Fatty Acids

Objective To verify the regulation of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT 2), which is associated with cholesterol metabolism, by saturated fatty acids (SFAs). Methods Palmitic acid (PA), the most abundant saturated fatty acid in plasma, and oleic acid (OA), a widely distributed unsaturated fatty acid, were used to treat hepatic cells HepG2, HuH7, and mouse primary hepatocytes. In addition, PA at different concentrations and PA treatment at different durations were applied in HepG2 cells. In in vivo experiment, three-month male C57/BL6 mice were fed with control diet and SFA diet containing hydrogenated coconut oil rich of SFAs. The mRNA level of ACAT2 in those hepatic cells and the mouse livers was detected with real-time polymerase chain reaction (PCR). Results In the three types of hepatic cells treated with PA, that SFA induced significant increase of ACAT2 expression (P<0.01), whereas treatment with OA showed no significant effect. That effect of PA was noticed gradually rising along with the increase of PA concentration and the extension of PA treatment duration (both P<0.05). SFA diet feeding in mice resulted in a short-term and transient increase of ACAT2 expression in vivo, with a peak level appearing in the mice fed with SFA diet for two days (P<0.05). Conclusion SFA may regulate ACAT2 expression in human and mouse hepatic cells and in mouse livers.

Sphingosine kinase 1 is upregulated with lysophosphatidic acid receptor 2 in human colorectal cancer

AIM: To examine the expression of Sph K1, an oncogenic kinase that produces sphingosine 1-phosphate(S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid(LPA) receptor overexpressed in various cancers, in human colorectal cancer.METHODS: Real-time reverse-transcription polymerase chain reaction was used to measure the m RNA expression of Sph K1, LPAR2, and the three major S1 P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of Sph K1 and LPAR2.RESULTS: C o l o r e c t a l c a n c e r t i s s u e i n 2 2 o f 2 7 patients had higher levels of Sph K1 m RNA than in normal tissue. In two-thirds of the samples, Sph K1 m RNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 m RNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1 P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between Sph K1 and LPAR2 expression [Pearson's correlation coefficient(r) = 0.784 and P < 0.01]. The m RNA levels of Sph K1 and LPAR2 did not correlate with TNM stage.CONCLUSION: Our findings suggest that S1 P andLPA may play important roles in the development ofcolorectal cancer via the upregulation of Sph K1 andLPAR2, both of which could serve as new therapeutictargets in the treatment of colorectal cancer.

production of extracellular lysophosphatidic acid in the regulation of adipocyte functions and liver fibrosis

Lysophosphatidic acid(LPA), a glycerophospholipid, consists of a glycerol backbone connected to a phosphate head group and an acyl chain linked to sn-1 or sn-2 position. In the circulation, LPA is in submillimolar range and mainly derived from hydrolysis of lysophosphatidylcholine, a process mediated by lysophospholipase D activity in proteins such as autotaxin(ATX). Intracellular and extracellular LPAs act as bioactive lipid mediators with diverse functions in almost every mammalian cell type. The binding of LPA to its receptors LPA1-6 activates multiple cellular processes such as migration, proliferation and survival. The production of LPA and activation of LPA receptor signaling pathways in the events of physiology and pathophysiology have attracted the interest of researchers. Results from studies using transgenic and gene knockout animals with alterations of ATX and LPA receptors genes, have revealed the roles of LPA signaling pathways in metabolic active tissues and organs. The present review was aimed to summarize recent progresses in the studies of extracellular and intracellular LPA production pathways. This includes the functional, structural and biochemical properties of ATX and LPA receptors. The potential roles of LPA production and LPA receptor signaling pathways in obesity, insulin resistance and liver fibrosis are also discussed.

Effects of lysophosphatidic acid on human periodontal ligament stem cells from teeth extracted from dental patients

Despite their potential applications in future regenerative medicine, periodontal ligament stem cells(PDLSCs) are difficult to obtain in large amounts from patients. Therefore, maintaining sternness while expanding the cell numbers for medical use is the key to transitioning PDLSCs from the bench to the clinic. Lysophosphatidic acid(LPA), which is present in the human body and saliva, is a signaling molecule derived from phospholipids. In this study, we examined the effects of LPA on sternness maintenance in human PDLSCs. Several spindle-shaped and fibroblast-like periodontal ligament stem-like cell lines were established from PDLSC isolation. Among these cell lines, the most morphologically appropriate cell line was characterized. The expression levels of OCT4, NANOG(a stem cell marker), and CD90(a mesenchymal stem cell marker) were high. However, CD73(a negative marker of mesenchymal stem cells) expression was not observed. Notably, immunofluorescence analysis identified the expression of STRO-1, CD146(a mesenchymal stem cell marker), and sex determining region Y-box 2 at the protein level. In addition, lipid droplets were stained by Oil red O after the induction of adipogenesis for 21 days, and mineralized nodules were stained by Alizarin Red S after the induction of osteogenesis for 14 days. Alkaline phosphate staining also demonstrated the occurrence of osteogenesis. In summary, we established a human PDLSC line, which could be applied as a cell source for tissue regeneration in dental patients. However, further studies are needed to determine the detailed effects of LPA on PDLSCs.

Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

AIM:To study the effects of lysophosphatidic acid(LPA) on proliferation,adhesion,migration,and apoptosis in the human colon cancer cell line,SW480,and its mechanisms of action. METHODS:Methyl tetrazolium assay was used to assess cell proliferation.Flow cytometry was employed to detect cell apoptosis.Cell migration was measured by using a Boyden transwell migration chamber.Cell adhesion assay was performed in 96-well plates according to protocol. RESULTS:LPA significantly stimulated SW480 cell proliferation in a dose-dependent and time-dependent manner compared with the control group(P<0.05) while the mitogen-activated protein kinase(MAPK)inhibitor,PD98059,significantly blocked the LPA stimulation effect on proliferation.LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner(P<0.05).Rho kinase inhibitor, Y-27632,significantly inhibited the up-regulatory effect of LPA on adhesion and migration(P<0.05).LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs,cisplatin and 5-FU(P<0.05), but the phosphoinositide 3-kinase(PI3K)inhibitor, LY294002,significantly blocked the protective effect of LPA on apoptosis. CONCLUSION:LPA stimulated proliferation,adhesion,migration of SW480 cells,and protected from apoptosis.The Ras/Raf-MAPK,G12/13-Rho-RhoA and PI3K- AKT/PKB signal pathways may be involved.

Yangxueqingnao particles inhibit rat vascular smooth muscle cell proliferation induced by lysophosphatidic acid

Objective: To observe the effect of Yangxueqingnao particles on rat vascular smooth muscle cell (VSMC) prolif- eration induced by lysophosphatidic acid (LPA). Methods: The amount of 3H-TdR (3H-thymidine) admixed in cultured rat VSMC was measured and mitogen-activated protein kinase (MAPK) activity and lipid peroxidation end product malondialdehyde (MDA) content of the VSMC were assayed. Results: 1×10?9, 1×10?8, 1×10?7 mol/L LPA in a concentration dependent manner, induced the amount of 3H-TdR admixed, MAP kinase activity, and MDA content of the cultured rat VSMC to increase. However, 5%, 10%, and 15% Yangxueqingnao serum preincubation resulted in a decrease of 23.0%, 42.0%, and 52.0% (P<0.01) respectively in the amount of 3H-TdR admixed, a decline in VSMC MAP kinase activity of 13.9% (P<0.05), 29.6% (P<0.01), and 48.9% (P<0.01) respectively, and also, a decrease in MDA content of VSMC of 19.4%, 24.7%, and 43.2% (P<0.01) respectively, in the 1×10?7 mol/L LPA-treated VSMC. Conclusions: LPA activates the proliferation and lipid peroxidation of VSMC in a concentration dependent manner. The LPA-induced VSMC proliferation is related to the activity of MAP kinases, enzymes involved in an intracellular signalling pathway. The results of the present study showed that Yangxueqingnao particles can effectively inhibit LPA-induced VSMC proliferation, MAP kinase activation, and reduce lipid peroxidative lesion.

KAI1/CD82 gene and autotaxin-lysophosphatidic acid axis in gastrointestinal cancers

The KAI1/CD82 gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and prognosis.Cell metabolism dysregulation is an important cause of tumor occurrence,development,and metastasis.As one of the important characteristics of tumors,cell metabolism dysregulation is attracting increasing research attention.Phospholipids are an indispensable substance in the metabolism in various tumor cells.Phospholipid metabolites have become important cell signaling molecules.The pathological role of lysophosphatidic acid(LPA)in tumors was identified in the early 1990s.Currently,LPA inhibitors have entered clinical trials but are not yet used in clinical treatment.Autotaxin(ATX)has lysophospholipase D(lysoPLD)activity and can regulate LPA levels in vivo.The LPA receptor family and ATX/lysoPLD are abnormally expressed in various gastrointestinal tumors.According to our recent pre-experimental results,KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating the ATX-LPA axis.However,no relevant research has been reported.Clarifying the mechanism of ATX-LPA in the inhibition of cancer metastasis by KAI1/CD82 will provide an important theoretical basis for targeted cancer therapy.In this paper,the molecular compositions of the KAI1/CD82 gene and the ATX-LPA axis,their physiological functions in tumors,and their roles in gastrointestinal cancers and target therapy are reviewed.

Lysophosphatidic acid transactivates both c-Met and epidermal growth factor receptor, and induces cyclooxygenase-2 expression in human colon cancer LoVo cells

AIM: To examine whether lysophosphatidic acid (LPA)induces phosphorylation of c-Met and epidermal growth factor receptor (EGFR), both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 (COX-2) expression in human colon cancer cells.METHODS: Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis,followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis.RESULTS: Immunoprecipitation analysis revealed that 10 μmol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 μmol/L LPA induced COX-2 expression in a dose-dependent manner.CONCLUSION: Our results suggest that LPA acts upstream of various receptor tyrosine kinases (RTKs) and COX-2,and thus may act as a potent stimulator of colorectal cancer.

Lysophosphatidic acid induced nuclear translocation of nuclear factor-κB in Panc-1 cells by mobilizing cytosolic free calcium

AIM: To clarify whether Lysophosphatidic acid (LPA) activates the nuclear translocation of nuclear factor-κB (NF-κB) in pancreatic cancer. METHODS: Panc-1, a human pancreatic cancer cell line, was used throughout the study. The expression of LPA receptors was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). Cytosolic free calcium was measured by fluorescent calcium indicator fura-2, and the localization of NF-κB was visualized by immunofluorescent method with or without various agents, which effect cell signaling. RESULTS: Panc-1 expressed LPA receptors, LPA1, LPA2 and LPA3. LPA caused the elevation of cytosolic free calcium dose-dependently. LPA also caused the nuclear translocation of NF-κB. Cytosolic free calcium was attenuated by pertussis toxin (PTX) and U73122, an inhibitor of phospholipase C. The translocation of NF-κB was similarly attenuated by PTX and U73122, but phorbol ester, an activator of protein kinase C, alone did not translocate NF-κB. Furthermore, the translocation of NF-κB was completely blocked by Ca2+ chelator BAPTA-AM. Thapsigargin, an endoplasmic- reticulum Ca2+-ATPase pump inhibitor, also promoted the translocation of NF-κB. Staurosporine, a proteinkinase C inhibitor, attenuated translocation of NF-κB induced by LPA. CONCLUSION: These findings suggest that protein kinase C is activated endogenously in Panc-1, and protein kinase C is essential for activating NF-κB with cytosolic calcium and that LPA induces the nuclear translocation of NF-κB in Panc-1 by mobilizing cytosolic free calcium.

Autotaxin and lysophosphatidic acid signalling in lung pathophysiology

Autotaxin(ATX or ENPP2) is a secreted glycoprotein widely present in biological fluids. ATX primarily functions as a plasma lysophospholipase D and is largely responsible for the bulk of lysophosphatidic acid(LPA) production in the plasma and at inflamed and/or malignant sites. LPA is a phospholipid mediator produced in various conditions both in cells and in biological fluids, and it evokes growth-factor-like responses, including cell growth, survival, differentiation and motility, in almost all cell types. The large variety of LPA effector functions is attributed to at least six G-protein coupled LPA receptors(LPARs) with overlapping specificities and widespread distribution. Increased ATX/LPA/LPAR levels have been detected in a large variety of cancers and transformed cell lines, as well as in non-malignant inflamed tissues, suggesting a possible involvement of ATX in chronic inflammatory disorders and cancer. In this review, we focus exclusively on the role of the ATX/LPA axis in pulmonary pathophysiology, analysing the effects of ATX/LPA on pulmonary cells and leukocytes in vitro and in the context of pulmonary pathophysi-ological situations in vivo and in human diseases.

LPA对牦牛卵丘细胞扩张因子HAS2、PTGS2和PTX3表达的影响

本研究以溶血磷脂酸(lysophosphatidic acid,LPA)在卵丘细胞扩张中的作用为切入点,旨在探讨不同浓度LPA对牦牛卵丘细胞(yak cumulus cells,YCCs)中卵丘扩张因子(透明质酸合成酶2(hyaluronate synthase 2,HAS2)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)和正五聚蛋白3(pentraxin 3,PTX3))表达的影响。本研究以健康成年(3~4岁)雌牦牛的YCCs为研究对象,取对数生长期的YCCs,将不同浓度的LPA(空白对照、阴性对照、5、15、30和50μmol·L^(-1))作用于体外培养的YCCs,分别培养12、24、36、48 h后,CCK-8检测YCCs的细胞活性,采用RT-qPCR和Western-blot法检测YCCs中HAS2、PTGS2和PTX3 mRNA和蛋白相对表达量,细胞免疫荧光染色法检测卵丘扩张因子HAS2、PTGS2和PTX3在YCCs中的分布。试验中每个处理组3个重复。结果显示,LPA孵育12、24、36和48 h,对YCCs的活性有着明显的促进作用。当孵育时间为24 h时,LPA对YCCs活性的促进作用最明显。相比较于对照组而言,当LPA浓度为15μmol·L^(-1)时,不同孵育时间中YCCs的活性提升最为显著(P<0.05)。当LPA浓度为15μmol·L^(-1)时,与空白对照组相比,HAS2、PTGS2和PTX3的mRNA和蛋白相对表达量最高(P<0.05),且YCCs中HAS2、PTGS2和PTX3的荧光强度明显增强。当LPA浓度大于15μmol·L^(-1)时,HAS2、PTGS2和PTX3的mRNA和蛋白相对表达量逐渐下降。本研究表明,LPA对YCCs活性具有促进作用。当孵育时间为24 h,并且LPA浓度为15μmol·L^(-1)时,活性提升最为显著(P<0.05)。LPA可以增强YCCs中卵丘扩张因子HAS2、PTGS2、PTX3的表达,且其作用浓度具有剂量依赖性,最佳浓度为15μmol·L^(-1)。研究结果为阐明LPA促进牦牛卵丘细胞扩张的分子机制提供了理论依据,为进一步提高牦牛卵母细胞的质量和体外受精(in vitro fertilization,IVF)成功率提供理论基础。

脑梗死患者脑脊液溶血磷脂酸水平与神经功能缺损状态的相关性分析

目的探讨与分析脑梗死(cerebral infarction,CI)患者脑脊液溶血磷脂酸(plasma lysophosphatidic acid,LPA)水平与神经功能缺损状态的相关性分析。方法选择2020年3月—2022年11月在北京市昌平区中西医结合医院诊治的67例脑梗死患者作为研究对象,所有患者在入院时进行神经功能缺损状态美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分,检测脑脊液溶血磷脂酸水平并进行相关性分析。结果在67例患者中,平均神经功能缺损状态NIHSS评分为(18.32±2.15)分,其中>21分17例(重度组)。重度组性别、身体质量指数、受教育程度、合并疾病等与非重度组对比,差异无统计学意义(P>0.05),重度组与非重度组的年龄、发病到入院时间等对比,差异有统计学意义(P<0.05)。重度组与非重度组的血糖、同型半胱氨酸、总胆固醇、甘油三酯含量对比,差异无统计学意义(P>0.05),重度组的低密度脂蛋白胆固醇含量高于非重度组,差异有统计学意义(P<0.05)。重度组的脑脊液溶血磷脂酸水平显著高于非重度组,差异有统计学意义(P<0.05)。Pearson分析显示NIHSS评分与年龄、发病到入院时间、脑脊液溶血磷脂酸水平都存在正相关性(P<0.05)。logistic回归分析显示年龄、发病到入院时间、脑脊液溶血磷脂酸水平为影响脑梗死患者NIHSS评分的重要因素(P<0.05)。结论脑梗死患者的神经功能缺损状态比较严重,神经功能缺损状态越差的脑梗死患者,脑脊液溶血磷脂酸水平越高,脑梗死患者脑脊液溶血磷脂酸水平与神经功能缺损状态存在相关性。

溶血磷脂酸对意大利蜜蜂进食的影响

【目的】探究肠道细菌代谢产物溶血磷脂酸(lysophosphatidic acid,LPA)对蜜蜂摄食行为的影响。【方法】对照组饲喂普通的蔗糖溶液,处理组饲喂含有LPA的蔗糖溶液,构建补充LPA的意大利蜜蜂Apis mellifera ligustica模型,利用群体水平取食测定法和个体水平取食测定法计算意大利蜜蜂6日龄成蜂的取食量,利用食物敏感度测定方法检测LPA对意大利蜜蜂成蜂食物敏感度的影响,最后对意大利蜜蜂成蜂的头、胸、腹和整个个体分别进行重量测定。【结果】LPA会减少意大利蜜蜂成蜂在群体水平上的取食量,对照组和处理组的群体水平每日平均取食量分别为4.23和2.38 mL。LPA不会影响意大利蜜蜂成蜂在群体水平上对食物的敏感度,也不会影响意大利蜜蜂成蜂在个体水平上对不适口食物的消耗量。分析不同饥饿水平意大利蜜蜂成蜂个体水平食物消耗量发现,LPA会使意大利蜜蜂成蜂个体水平上的饥饿感钝化,即使是饥饿状态下,处理组成蜂的取食量未能达到对照组的正常水平。对比意大利蜜蜂成蜂头、胸、腹和整个个体的重量发现,LPA降低成蜂的食物摄入导致头、胸、腹和整个个体重量显著下降。【结论】蜜蜂肠道细菌的代谢产物LPA会抑制宿主意大利蜜蜂成蜂的食物摄入,进而引起体重下降。

慢性阻塞性肺疾病患者血浆溶血磷脂酸和可溶性ST2的表达水平及其临床意义

目的研究慢性阻塞性肺疾病(COPD)患者血浆中溶血磷脂酸(LPA)、可溶性ST2(sST2)的表达水平及其临床意义。方法选取本院2021年10月-2022年6月收治的42例急性加重COPD患者作为急性加重期组,接受治疗后,将其纳入稳定期组,并将40例健康受试者纳入对照组。收集各组的基本资料及外周血,检测COPD患者及对照组的肺功能,并通过酶联免疫吸附法检测血浆中LPA和sST2水平。结果COPD急性加重期的LPA、sST2水平均高于稳定期组,差异有统计学意义(均P<0.05);急性加重期和稳定期的LPA、sST2水平均高于对照组,差异有统计学意义(均P<0.05);在急性加重期和稳定期,LPA水平均与sST2水平呈正相关;急性加重期LPA、sST2水平与白细胞计数、中性粒细胞百分比、红细胞分布宽度、中性粒细胞与淋巴细胞比率、白蛋白呈正相关,LPA水平与单核细胞与高密度脂蛋白比率呈正相关,sST2水平与嗜酸性粒细胞计数呈正相关;稳定期LPA、sST2水平与第1秒用力呼气容积占预计值百分比(FEV1%pred)、第1秒用力呼气容积/用力肺活量比值(FEV1/FVC)呈负相关,与白细胞计数、中性粒细胞百分比、红细胞分布宽度、中性粒细胞/淋巴细胞比率呈正相关,LPA水平与血小板/淋巴细胞比率呈正相关,sST2水平与嗜酸性粒细胞计数、白蛋白呈正相关。结论LPA和sST2的水平在COPD患者外周血中升高,两者水平呈正相关,并且与肺功能、临床指标相关,提示LPA和sST2可能共同参与慢阻肺的发生发展。

血浆溶血磷脂酸受体1水平对高血压脑出血患者预后的预测价值

【目的】探讨血浆溶血磷脂酸受体1(LPAR1)水平对高血压脑出血患者预后的预测价值。【方法】选择2016年3月至2020年3月本院收治的130例高血压脑出血患者(观察组),另选同期在本院体检的50例健康者为对照组。采用酶联免疫吸附法检测两组血浆LPAR1水平,根据观察组患者发病30 d后的格拉斯哥预后量表(GOS)评分分为预后良好组(n=67)和预后不良组(n=63)。观察组患者的预后不良影响因素采用多因素Logistic回归进行分析,绘制受试者工作特征(ROC)曲线,评估血浆LPAR1水平与高血压脑出血患者预后不良的预测价值。【结果】观察组血浆LPAR1水平高于对照组,差异有统计学意义(P<0.05)。预后良好组、预后不良组患者的出血量、美国国立卫生研究院卒中量表(NIHSS)评分及治疗方案比较,差异有统计学意义(P<0.05)。预后不良组患者血浆LPAR1水平高于预后良好组,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,LPAR1>4.22μg/L、NIHSS评分>(23.62±2.55)分均是高血压脑出血患者预后不良的独立危险因素(P<0.05)。ROC曲线分析显示,血浆LPAR1水平诊断高血压脑出血疾病患者预后不良的AUC为0.857(95%CI:0.753~0.869),截断值为3.68μmol/L,其灵敏度、特异度分别为81.3%、85.6%。【结论】血浆LPAR1水平对高血压脑出血疾病患者预后有一定预测价值,可为临床早期评估患者预后提供一定参考。

加味补阳还五汤联合依达拉奉对急性脑梗死患者血浆溶血磷脂酸水平的影响

目的 探讨加味补阳还五汤联合依达拉奉对急性脑梗死患者血浆溶血磷脂酸水平的影响。方法 随机选取衡阳市中医医院于2021年3月—2023年3月收治的80例急性脑梗死患者为研究对象,依据不同治疗方法分为治疗组与对照组,每组40例,对照组采用依达拉奉治疗,治疗组采用加味补阳还五汤与依达拉奉联合治疗,比较两组的治疗效果。结果 治疗前,两组患者血浆溶血磷脂酸水平对比,差异无统计学意义(P>0.05);治疗后3、5、7、14 d,治疗组患者血浆溶血磷脂酸水平低于对照组,差异有统计学意义(P均<0.05)。治疗组治疗总有效率为92.50%,高于对照组的75.00%,差异有统计学意义(χ^(2)=4.501,P<0.05)。结论 急性脑梗死患者进行加味补阳还五汤联合依达拉奉治疗效果明显,能够有效降低血浆溶血磷脂酸水平,对抑制血小板聚集。

Conjugated Linoleic Acid and Dietary Fats Differentially Affect Hepatic ACAT Activity and LDL-Cholesterol in Postweanling Pigs Fed Low-Fat Diets

ABSTRACT：Two separate studies tested the hypoth- esis that plasma low-density lipoprotein cholesterol LDL-C ） can be decreased by conjugated linoleic acid （CLA） by depressing hepatic acyl-coenzyme A： cholesterol acyltransferase （ACAT） activity. In the first experiment, 3 groups of 6 early-weaned piglets were fed low-fat diets containing either 1.5% CLA, 1.5% corn oil or 1.5% beef tallow;fat provided 8% of the energy intake. In the second experiment, 4 groups of 6 early-weaned piglets were fed high-fat di- ets containing either 15% beef tallow, 12% beef tal- low plus 3% CLA, 15% corn oil, or 12% corn oil plus 3% CLA; fat provided 29% of energy intake. Cholesterol was balanced across diets in both experi-ments. In pigs fed the low-fat diets, all dietary fats in- creased LDL-C and triacylglycerols and decreased high-density lipoprotein cholesterol （ HDL-C ） and very low-density lipoprotein cholesterol （VLDL-C）. LDL-C was the same in pigs fed low-fat tallow or low-fat CLA diets. However, ACAT activity was near- ly 80% higher in pigs fed the low-fat tallow diet than in pigs fed the low-fat CLA diets. All high-fat diets increased LDL-C, HDL-C and triacylglycerols equally with no effect on VLDL-C. There were no unique fat- ty acid effects of the high-fat diets on ACAT activity. We conclude that supplemental fats had differential effects on hepatic ACAT activity and LDL-C, but on- ly in pigs fed low-fat diets.

原发性肝癌患者血清FGF19、GP73、LPA的水平及临床意义

目的探讨血清成纤维细胞生长因子19(FGF19)、高尔基体跨膜糖蛋白73(GP73)和溶血磷脂酸(LPA)在原发性肝癌患者中的水平及临床意义。方法将2020年5月至2023年5月诊治的106例原发性肝癌患者设为观察组,选取同期53例健康体检者设为对照组,对比两组的血清FGF19、GP73、LPA水平变化;采用Kendall′s tau-b法分析FGF19、GP73、LPA水平与原发性肝癌患者临床病理特征的相关性;Logistic回归模型和受试者工作特征(ROC)曲线分析FGF19、GP73、LPA联合诊断原发性肝癌的效能。结果观察组的FGF19、GP73、LPA水平均高于对照组(P<0.05)。不同TNM分期、分化程度、淋巴结转移患者的血清FGF19、GP73、LPA水平比较,差异有统计学意义(P<0.05)。FGF19、GP73、LPA水平与TNM分期、分化程度、淋巴结转移呈正相关(P<0.05)。ROC曲线分析显示,FGF19、GP73、LPA及三项联合诊断原发性肝癌的曲线下面积分别为0.833、0.846、0.864和0.945,敏感度分别为77.40%、82.10%、94.30%和92.50%,特异度分别为83.00%、79.20%、81.10%和83.00%。结论血清FGF19、GP73、LPA在原发性肝癌患者中呈异常表达,监测其水平变化有助于为及时发现原发性肝癌提供重要依据。

CXCL10、LPA蛋白在卵巢癌组织中的表达及与预后的关系

目的 分析CXC趋化因子配体10(CXCL10)、溶血磷脂酸(LPA)蛋白在卵巢癌组织中的表达及与预后的关系。方法 选取2017年1月—2019年12月行卵巢切除术的103例原发性卵巢癌以及同期60例卵巢良性肿瘤为研究对象。所有患者术后取卵巢组织标本,采用免疫组化法检测CXCL10、LPA蛋白表达情况。比较不同卵巢组织CXCL10、LPA蛋白表达情况,分析CXCL10、LPA蛋白表达与卵巢癌患者临床特征及预后的关系。结果 卵巢癌组织CXCL10、LPA蛋白阳性表达率分别为68.93%(71/103)、75.73%(78/103),高于卵巢良性肿瘤组织的26.67%(16/60)、33.33%(20/60)(P<0.05);CXCL10、LPA蛋白表达与卵巢癌分化程度、国际妇产科联合会分期、腹水、淋巴结转移、肿瘤直径有关(P<0.05,P<0.01),而与年龄、组织学类型无关(P>0.05)。Kaplan-Meier生存曲线分析结果显示,CXCL10、LPA蛋白阳性表达组3年无进展生存率分别为23.94%、20.51%,低于阴性表达组的40.63%、56.00%(P<0.05)。结论 卵巢癌组织中CXCL10与LPA蛋白呈高表达状态,不同临床特征卵巢癌患者CXCL10与LPA蛋白表达存在差异,二者与预后有关。