Delineation of fatty acid metabolism in gastric cancer:Therapeutic implications

BACKGROUND The prognosis of gastric cancer is extremely poor.Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.AIM To illustrate fatty acid metabolic mechanisms in gastric cancer,detect core genes,develop a prognostic model,and provide treatment options.METHODS Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed.Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis.Then,patients from The Cancer Genome Atlas were assigned to high-and low-risk cohorts according to the mean value of the risk score as the threshold,which was verified in the Gene Expression Omnibus database.Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed.RESULTS An integrated evaluation was performed in this study.Fatty acid metabolismrelated genes were used to construct the risk model.Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the“pRRophetic”R package.Patients in the high-risk cohort were associated with type Ⅰ/Ⅱ interferon activation,increased inflammation level,immune cell infiltration,and tumor immune dysfunction based on the exclusion algorithm,indicating the potential benefit of immunotherapy in these patients.CONCLUSION We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis,chemotherapy sensitivity,and immunotherapy.

Metabolic profile analysis of free amino acids in experimental autoimmune uveoretinitis rat plasma

AIM: To determine the differences of amino acid(AA) levels in experimental autoimmune uveoretinitis(EAU). METHODS: AA analysis of the plasma samples in EAU rats induced by interphotoreceptor retinoid-binding protein emulsion were performed with high performance liquid chromatography(HPLC) and phenylisothiocyanate(PITC) pre-column derivation methods were performed. Using partial least squares discriminant analysis(PLS-DA), the potential biomarkers were identified in EAU rat plasma, and the metabolic pathways related to EAU were further analyzed. RESULTS: The method results showed that linear(r≥0.9957), intra-day reproducible [relative standard deviation(RSD)=0.04%-1.33%], inter-day reproducible(RSD=0.06%-2.07%), repeatability(RSD=0.03%-0.89%), stability(RSD=0.05%-2.48%) and recovery(RSD=1.98%-4.39%), with detection limits of 0.853-11.4 ng/mL. The metabolic profile in EAU rats was different from that in the control groups five AAs concentrations were increased and nine AAs were reduced. Moreover, five metabolic pathways were related to the development of EAU. CONCLUSION: The developed method is a simple, rapid and convenient for determination of AAs in EAU rat plasma, and these findings will provide a comprehensiveinsight on the metabolic profiling of the pathological changes in EAU.

Effects of daily nitrogen and phosphorus input on planktonic community metabolism in a semi-enclosed bay by mesocosm experiment

Planktonic metabolism plays an important role in affecting the energy transportation and carbon cycle of the marine ecosystem.However,its regulation mechanism remains unclear under the continuously exogenous nutrient inputs in nearshore waters.In this study,a mesocosm experiment was conducted in a semi-enclosed bay,the Daya Bay,to explore the responses of plankton metabolic balance and community structure to a concentration gradient of daily nitrogen and phosphorus inputs.The results showed that nutrient enrichments promoted phytoplankton biomass,total primary production,and community respiration,and the promoting effect enhanced alongwith the increase of nutrient concentration.However,the net community production fluctuated more violently between autotrophic and heterotrophic with the increase of nutrient inputs and tended to be more heterotrophic from the 5 th day to the 10 th day of the experiment.In addition,the daily flux of nitrogen and phosphorus,2μmol/(L·d)and 0.066μmol/(L·d),respectively,could be regarded as a potential threshold for ecosystem stability and health,since most of the ecological characteristics related to plankton structure and function have undergone significant changes when the nutrient level is higher than that.In the nearshore enclosed or semi-enclosed waters,nutrient from continuous terrigenous input is likely to be concentrated and exceed this level,indicating the ecological risks due to the metabolic unbalance and the deterioration of plankton community structure.

An experimental proposal for low order laboratory animals’ extension of metabolic life

Essential bibliography, with therein references included, is presented owing to the contribution of the author groups to Mitochondrial Filamentation, which is a new emerging field of physiological energy metabolism. These studies provide the first seed concept for trials to extend the metabolic life, for a few days, in low order laboratory mammals killed by electrocution, as a first type of accidental death. It is proposed, essentially, to cool out the corpses very soon after death at 12oC-14oC and take advantage of the effect super magnetism to counteract the force of gravity to install a net recurrent cycle of oxygen consumption and oxygen production by filamented mitochondria in all the organism tissues. Once the cause of death had been corrected adequately, it is possible to try the reanimation to experience the full life of the corpse with highly sophisticated methodology.

Free radicals in development of experimental gastric carcinoma and precan cerous lesions in ducedby N-methyl-N'-nitro-N-nitrosoguanidine in rats

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Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma

INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.

Inhibitory effects of two oligosaccharideson murine melanoma experimental liver metastasis

AIM To observe the effects of a chemically synthesized tetrose and a natural yeast mannan on experimental liver metastasis of mouse melanoma. METHODS After treated with 4mg tetrose (tetrose group) or 4mg mannan (mannan group) for 30 minutes at 37℃, 0 5ml 1×10 6 B16 MBK melanoma cells were injected into the spleen of mice. Fifty five days later, melanoma metastatic nodes on the surface of the liver and in other organs as well as mouse survival time were observed. RESULTS Of the 6 mice in control (B16 cell+PBS) group, 4 died naturally within 55 days, and 2 were killed on the 55th day. All of the 6 mice had metastases in livers, the total number of the melanoma nodes on each liver surface ranged from 2 to 30, with the largest one merging into the whole liver. One mouse had a neoplasm in the remnant site of injection, and 3 had metastases in lungs. In contrast, of the 6 mice in tetrose group, only one died on the 50th day after injection, with 3 metastases in the liver, the largest being 10mm in diameter, the other 5 mice survived until being dissected on the 55th day after injection and had no liver metastasis, but 3 of them had neoplasms in their remnant sites of injection. In mannan group, all of the 6 mice survived and no metastasis was seen except for 2 liver nodes in one mouse with the largest diameter of 1mm. Neither tetrose nor mannan group had metastasis out of the liver, and the weight of liver in the two groups was significantly lower than those in the control group. CONCLUSION Both tetrose and mannan had the effects of preventing melanoma cells from experimental metastasis to and out of the liver, and prolonging the survival time of the mouse.

Diffusion tensor imaging and proton magnetic resonance spectroscopy in brain tumor Correlation between structure and metabolism

Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individual fractional anisotropy values with N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in tumors, edema, and normal white matter. This study divided the brain parenchyma into tumor, pedtumoral edema, and normal-appearing white matter according to MRI data, and analyzed the correlation of metabolites with water molecular diffusion. Results demonstrated that in normal-appearing white matter, N-acetylaspartate/creatine ratios were positively correlated with fractional anisotropy values, negatively correlated with radial diffusivities, and positively correlated with maximum eigenvalues. Maximum eigenvalues and radial diffusivities in peritumoral edema showed a negative correlation with choline, N-acetylaspartate, and creatine. Radial diffusivities in tumor demonstrated a negative correlation with choline. These data suggest that the relationship between metabolism and structure is markedly changed from normal white matter to peritumoral edema and tumor. Neural metabolism in the peritumoral edema area decreased with expanding extracellular space. The normal relationship of neural function and microstructure disappeared in the tumor region.

Way back for fructose and liver metabolism:Bench side to molecular insights

The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy.The consumption of sugarsweetened beverages is the main source of added sugars.Fructose,together with glucose,as a component of high fructose corn syrups or as a component of the sucrose molecule,is one of the main sweeteners present in this kind of beverages.Data from prospective and intervention studies clearly point to high fructose consumption,mainly in the form of sweetened beverages,as a risk factor for several metabolic diseases in humans.The incidence of hypertension,nonalcoholic fatty liver disease(NAFLD),dyslipidemia(mainly hypertriglyceridemia),insulin resistance,type 2 diabetes mellitus,obesity,and the cluster of many of these pathologies in the form of metabolic syndrome is higher in human population segments that show high intake of fructose.Adolescent and young adults from lowincome families are especially at risk.We recently reviewed evidence from experimental animals and human data that confirms the deleterious effect of fructose on lipid and glucose metabolism.In this present review we update the information generated in the past 2 years about high consumption of fructose-enriched beverages and the occurrence of metabolic disturbances,especially NAFLD,type 2 diabetes mellitus,and metabolic syndrome.We have explored recent data from observational and experimental human studies,as well as experimental data from animal and cell models.Finally,using information generated in our laboratory and others,we provide a view of the molecular mechanisms that may be specifically involved in the development of liver lipid and glucose metabolic alterations after fructose consumption in liquid form.

Immunohistochemical study on expression of epidermal growth factor receptor at hepatocyte nuclei in experimental rat liver cirrhosis

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TUMOR NECROSIS FACTOR－α ALTERS PROTEINMETABOLISM AND CELL－CYCLE KINETICSIN MALIGNANT TUMOR

The effects of tumor necrosis factor-α(TNF) on protein metabolism and cell-cycle kinetics were investigated in malignant tumor. Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma,were injected intraperitoneally with recombinant human TNF at a dose of 4-75×106 U/kg for 3 consecutive days.Tumor protein metabolism and cell-cycle kinetics were analyzed. The results showed a significant decrease in tumor volume and weight in comparison with control.TNF resulted in significant decrease in tumor Protein fractional synthesis rate, Protein synthesis and fractional growth rate, but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index and GI phase increase of tumor cells, 6 hours after bromodeoxyuridine injection, by cytometry. The results indicated that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.

新形势下护理《生物化学》思政育人教学实践——以糖代谢为例

物质代谢与调节在生物化学课程中是比较重要的章节,属于重难点内容之一,糖代谢是物质代谢的最开始讲授的内容,学好糖代谢,对其它后续课程知识具有积极的促进作用。随着新高考的改革,目前本科护理专业学生的生物化学基础知识薄弱,且专业思想不稳定。本项目结合时事新闻热点、科研精神、学校特色的人文精神,把集体主义、奋斗精神、社会行为规范、社会主义核心价值观、对立统一和否定之否定原理等,融入糖代谢的理论和实验教学中。经过两年的实施,学生满意度高,教学成效明显,为护理生物化学的思政教学提供一定借鉴。

益气活血法对慢性心力衰竭大鼠心肌能量代谢及炎性因子的影响

目的:基于益气活血法探讨全真一气汤合补阳还五汤对慢性心力衰竭(CHF)大鼠心肌能量代谢及炎性因子的影响。方法:将30只健康雄性SD大鼠随机分为对照组、模型组和中药组,每组10只。采用腹腔注射阿霉素制备CHF模型,中药组给予全真一气汤合补阳还五汤干预。采用酶联免疫吸附法(ELISA)检测三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)、白细胞介素6(IL-6)、N末端脑钠肽前体(NT-proBNP)水平;采用逆转录定量聚合酶链式反应(qRT-PCR)检测miR-21水平。结果:与对照组比较,模型组ATP、ADP、AMP降低(P<0.05),IL-6、NT-proBNP、miR-21表达均升高(P<0.05);与模型组比较,中药组ATP、ADP、AMP均升高(P<0.05),IL-6、NT-proBNP、miR-21表达均降低(P<0.05)。结论:益气活血法治疗可提高CHF大鼠心肌能量供应,减轻炎症反应,改善心功能。

不同双能CT虚拟单能谱图像衍生影像组学特征的可重复性:实验研究

目的比较3种双能CT(DECT)系统在不同条件下所获VX2兔肝肿瘤模型虚拟单能谱图像(VMI)增强CT影像组学特征(RF)的可重复性及其与诊断效能的关系。方法将15只VX2兔肝肿瘤模型随机均分为3组,分别接受采用双源DECT(dsDECT)、快速kV切换DECT(rsDECT)或双层探测器DECT(dlDECT)于不同体积CT剂量指数(CTDIvol)(6、9及12 mGy)下腹部增强CT扫描,于40~140 keV内每间隔10 keV重建单能图像并提取RF;以组内相关系数(ICC)计算RF可重复性,以ICC≥0.80为可重复RF,比较不同CT仪配对之间及不同CTDIvol下可重复RF占比(R),以及相同CTDIvol下不同CT仪配对可重复RF数量(N)最大值相应重建能量水平;绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),比较最佳可重复条件下可重复RF与其他RF的诊断效能,计算RF的ICC与相应AUC的Spearman相关系数。结果R rsDECT-dsDECT[6.45%,95%CI(2.36%,8.87%)]高于R dlDECT-dsDECT[0.72%,95%CI(0.15%,1.79%)]及R rsDECT-dlDECT[1.43%,95%CI(0.60%,4.06%)](校正P均<0.05);R_(9mGy)[3.70%,95%CI(1.31%,5.73%)]及R_(12mGy)[2.63%,95%CI(0.60%,6.69%)]高于R_(6mGy)[1.31%,95%CI(0.12%,1.55%)](校正P均<0.05)。6、9及12 mGy下,RF最佳可重复重建能量水平集中于50~70 keV,可重复RF的AUC均高于其他RF(校正P均<0.05),且RF可重复性与诊断效能相关(r s=0.102~0.516,P<0.05)。结论兔肝肿瘤模型VMI CT增强图像RF可重复性与DECT设备、CTDIvol水平及重建能量水平相关,可重复RF可能诊断效能更佳。

基于整合药理学和实验验证探讨健脾除痰解毒方干预肺癌的作用机制

基于整合药理学和实验验证探讨健脾除痰解毒方(Jianpi Chutan Jiedu Decoction,JCJD)干预肺癌的作用机制。采用中医药整合药理学研究平台(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,TCMIP)V2.0,检索并获取健脾除痰解毒方靶标及功能信息,以及肺癌疾病靶标及功能信息,借助中医关联网络挖掘平台构建“疾病-方剂”关联网络,并通过网络拓扑特征计算、自定义多维关联网络可视化(方剂-中药材-核心靶标-通路-疾病)以及基因本体(GO)功能和依托Reactome数据库的Pathway信息进行富集分析,发现健脾除痰解毒方干预肺癌的关键网络靶标及其作用机制。最后通过动物实验进一步验证整合药理学结果。结果共获得健脾除痰解毒方干预肺癌的核心靶标53个;GO富集分析得到生物过程有20种条目,细胞组分有11种条目,分子功能有20种条目;Reactome Pathway富集分析得到11个条目,主要涉及呼吸电子传递、TP53调节代谢基因、细胞内受体的SUMO化、白细胞介素(IL)-4和IL-13通路等信号通路。动物实验结果显示与模型组比较,联合组肿瘤组织中乳酸含量明显下降(P<0.05),联合组可明显上调肿瘤组织中磷酸酯酶与张力蛋白同源物(PTEN)蛋白平均光密度值(P<0.05),降低丙酮酸激酶M2(PKM2)和己糖激酶2(HK2)蛋白平均光密度值(P<0.05);与模型组比较,联合组可明显上调肿瘤组织中肿瘤抑制蛋白(P53)、PTEN mRNA及蛋白表达(P<0.01,P<0.05),降低肿瘤组织中TP53诱导的糖酵解与凋亡调控因子(TIGAR)、葡萄糖转运蛋白1(GLUT1)、PKM2、HK2 mRNA及蛋白表达(P<0.01)。综上,健脾除痰解毒方通过TP53调节代谢基因来下调葡萄糖代谢,从而抑制肺癌增殖。

超声分子影像组学评估前列腺癌前列腺特异膜抗原表达:实验研究

目的 观察超声分子影像组学评估前列腺癌(PCa)前列腺特异膜抗原(PSMA)表达的价值。方法 分别于裸鼠皮下接种22RV1细胞(PSMA阳性表达,n=9)或PC-3细胞(PSMA阴性表达,n=10),构建不同PSMA表达水平人前列腺癌细胞移植瘤裸鼠模型。制备靶向PSMA的超声纳米泡(PSMA-NB),进行表征检测及体内、外超声分子成像。以7∶3比例将裸鼠随机分为训练集及测试集,提取训练集纹理特征,以组内相关系数、单因素分析、最小绝对收缩和选择算子等方法筛选特征,构建超声分子影像组学模型,并评估模型诊断PSMA阳性PCa的效能。结果 所制备PSMA-NB平均粒径为(392.2±31.56)nm, Zeta电位为(-29.3±0.95)mV,体外显像效果理想,稳定性好。共基于训练集数据提取1 561个纹理特征,最终筛选出3个特征,包括exponential_glszm_ZoneVariance、wavelet_HHH_gldm_SmallDependenceLowGrayLevelEmphasis及logarithm_gldm_DependenceVariance,以之构建的超声分子影像组学模型诊断训练集、测试集PSMA阳性表达PCa的曲线下面积分别为0.950、0.875。结论 基于靶向PSMA超声分子影像组学模型可用于评估PCa裸鼠PSMA表达。

脂代谢重编程与原发性肝癌发生发展的关系

脂质代谢作为维持生命之本,是保持细胞存活的前提,脂质稳态能迅速对代谢变化做出协调反应。在癌症发生发展过程中,为了满足质膜合成和能量产生,癌细胞的脂质代谢会升高。脂质代谢异常对原发性肝癌的进展起着重要作用。本文综述二者之间的关联,以期寻找进一步防治原发性肝癌的靶点。

脑梗死脂质代谢基因鉴定及活血荣络方的干预作用

目的鉴定脑梗死脂质代谢基因,并探讨活血荣络方的干预作用。方法采用多芯片联合差异分析(GSE61616、GSE30655),结合Reactome数据库,鉴定出脑梗死脂质代谢基因,并在GSE97537芯片中鉴定并验证脑梗死脂质代谢基因的表达差异;采用Pearson相关性分析GSE61616、GSE30655、GSE97537、GSE137595、GSE22255、GSE163614、GSE78731数据集中51个脑梗死样本mRNA表达相关性;通过STRING数据库、R语言clusterProfiler包对脑梗死脂质代谢基因进行蛋白相互作用及GO、KEGG富集分析。制备脑梗死模型大鼠,并予活血荣络方浸膏11.7 g/kg灌胃给药,连续7 d,观察大鼠神经功能缺损症状、Nissl小体变化及脑梗死脂质代谢关键基因PLA2G4A、SPHK1、PTGS1 mRNA表达。结果TSPO、CYP1B1、PLIN2、CH25H、PLA2G4A、ANGPTL4、PTGS1、SPHK1、PTGES被鉴定为脑梗死脂质代谢基因,在脑梗死中显著高表达且显著正相关,其中PTGS1、PLA2G4A、SPHK1相互作用关系最强,是脑梗死脂质代谢关键基因;脑梗死脂质代谢基因主要发挥氧化还原酶活性、铁离子结合、血红素结合等分子功能,介导花生四烯酸代谢、磷脂酶D信号通路、VEGF信号通路,参与脂质代谢调控进程、脂肪酸代谢进程、脂肪酸衍生物代谢过程。脑梗死模型大鼠神经功能缺损症状严重(P<0.001),活血荣络方能有效改善模型大鼠神经功能缺损(P<0.001);Nissl染色结果提示,脑梗死后神经元结构异常,数目明显减少(P<0.001),活血荣络方能增加神经元数目(P<0.001),修复神经元结构;RT-qPCR结果提示,脑梗死脂质代谢关键基因在脑梗死中显著高表达(P<0.001),与生物信息学结果一致,活血荣络方能降低脂质代谢关键基因PTGS1、PLA2G4A、SPHK1表达(P<0.001,P<0.01,P<0.05)。结论活血荣络方能下调PTGS1、PLA2G4A、SPHK1表达,发挥氧化还原酶活性、铁离子结合、血红素结合等分子功能,介导花生四烯酸代谢、磷脂酶D信号通路、VEGF信号通路,参与脂质代谢调控进程、脂肪酸代谢进程、脂肪酸衍生物代谢过程,增加Nissl小体数目,改善神经功能缺损症状,发挥神经保护作用。

双酚类化合物的生物代谢机理研究进展

以双酚A(bisphenol A,简称BPA)及其替代物为代表的双酚类化合物(bisphenols,简称BPs)在各种环境介质、食品、消费品以及人类和动物体中被广泛检出,表明BPs存在全球性大规模污染趋势.除了BPs自身毒性外,其在生物体内的转化代谢产物可能具有比母体化合物更复杂的内分泌干扰效应和毒性效应,对于人体生命健康的影响不容小觑.本文就BPs生物代谢的实验和理论计算研究方法及其取得的研究成果等方面进行回顾总结,在分析现有研究存在的问题和不足上对未来的研究重点提出了展望.