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1.
林笑晗  贲腾  田尧  马林 《转化医学杂志》2022,11(4):233-236+217
目的 探究复方蛋氨酸胆碱结合苦黄注射液在酒精性脂肪肝治疗中的疗效及对肝纤维化的影响。方法 按照随机数字表法将2019年1月至2021年12月海安市人民医院收治并确诊的104例酒精性脂肪肝患者分为对照组和观察组,各52例。对照组给予复方蛋氨酸胆碱治疗,观察组苦黄注射液联合复方蛋氨酸胆碱治疗。两组患者均连续治疗1个月。采用全自动生化分析仪检测两组患者治疗前后血清丙氨酸转移酶(alanine transferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、总胆固醇(total cholesterol ,TC)、三酰甘油(triacylglycerol,TG)、总胆红素(total bilirubin,TBil)水平;采用放射免疫法检测两组患者治疗前后血清层粘连蛋白(laminin,LN)、透明质酸(hyaluronic acid,HA)、Ⅲ型前胶原N端肽(type III procollagen N-terminal peptide,PC Ⅲ)及Ⅳ型胶原(type IV collagen,Ⅳ-C)水平。比较两组患者的临床症状改善情况、临床疗效、肝功能指标及肝纤维化指标。结果 观察组治疗后的腹胀、肝区不适、黄疸、痞满等症状消失时间分别为(3.9±0.1) d、(9.8±0.2) d、(11.5±0.7)d、(3.8±0.2) d,均短于对照组分别为(7.5±0.3) d、(14.3±0.4) d、(15.6±0.8) d、(7.4±0.3) d(均P<0.05)。观察组临床总有效率高于对照组(94.2% vs 78.9%)(χ2=5.283,P=0.022)。观察组ALT、AST、TC、TG、TBil水平分别为(31.5±5.3) IU/L、(36.4±3.4) IU/L、(4.1±0.2) mmol/L、(1.4±0.3) mmol/L、(12.6±3.1) μmol/L,低于对照组[分别为(57.4±5.6) IU/L、(54.7±3.5) IU/L、(6.4±0.4) mmol/L、(2.6±0.5) mmol/L、(21.2±5.3) μmol/L](均P<0.05)。观察组治疗后LN、HA、PC Ⅲ、Ⅳ-C水平分别为(51.6±9.4) μg/L、(32.5±7.4) μg/L、(7.5±1.8) ng/mL、(32.3±4.2) μg/L,均低于对照组[分别为(80.5±10.3) μg/L、(58.7±12.2) μg/L、(16.5±3.6) ng/mL、(71.2±8.6) μg/L](均P<0.05)。对照组和观察组不良反应发生率分别为7.68%、3.84%,两组比较无明显差异(χ2=0.707,P=0.400)。结论 复方蛋氨酸胆碱结合苦黄注射液在酒精性脂肪肝患者中的治疗疗效显著,可改善患者的临床症状和肝功能,延缓肝纤维化的进程,安全性高。  相似文献   
2.
Proton magnetic resonance spectroscopy (MRS) is a promising noninvasive diagnostic technique for investigation of breast cancer metabolism. Spectroscopic imaging data may be obtained following contrast‐enhanced MRI by applying the point‐resolved spectroscopy sequence (PRESS) or the stimulated echo acquisition mode (STEAM) sequence from the MR voxel encompassing the breast lesion. Total choline signal (tCho) measured in vivo using either a qualitative or quantitative approach has been used as a diagnostic test in the workup of malignant breast lesions. In addition to tCho metabolites, other relevant metabolites, including multiple lipids, can be detected and monitored. MRS has been heavily investigated as an adjunct to morphologic and dynamic MRI to improve diagnostic accuracy in breast cancer, obviating unnecessary benign biopsies. Besides its use in the staging of breast cancer, other promising applications have been recently investigated, including the assessment of treatment response and therapy monitoring. This review provides guidance on spectroscopic acquisition and quantification methods and highlights current and evolving clinical applications of proton MRS. Level of Evidence 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.  相似文献   
3.
《药学学报(英文版)》2020,10(10):1926-1942
Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses.  相似文献   
4.
BACKGROUND Arachidyl amido cholanoic acid(Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis. In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH), 52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c, an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model [induced with a 0.1% methionine and choline deficient diet(0.1 MCD)] after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20 μmol/L Aramchol or vehicle for 48 h. Subsequently, analyses were performed including Western blot, proteomics by mass spectrometry, and fluxomic analysis with ~(13)C-uniformly labeled glucose. For the in vivo part of the study, male C57 BL/6 J mice were randomly fed a control or 0.1 MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk. Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes. This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA) synthesis and oxidation [PACCα/β(S79), SCD1, CPT1A/B, HADHA, and HADHB], oxidative phosphorylation(NDUFA9, NDUFB11, NDUFS1, NDUFV1, ETFDH, and UQCRC2), tricarboxylic acid(TCA) cycle(MDH2, SUCLA2, and SUCLG2), and ribosome(P-p70S6K[T389] and P-S6[S235/S236]). Flux experiments with ~(13)C uniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes, as indicated by the increase in the number of rounds that malate remained in the TCA cycle. Finally, liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1 MCD fed mice in a dose-dependent manner, showing normalization of glucose, G6P, F6P, UDP-glucose, and Rbl5 P/Xyl5 P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1, which in turn activate FA β-oxidation and oxidative phosphorylation.  相似文献   
5.
6.
李珍  倪娟  周滔  王晗  汪旭 《癌变.畸变.突变》2015,27(3):197-201,206
目的:探讨不同还原态叶酸和胆碱对人结肠腺癌细胞DNA错配修复基因hMLH1和hMSH2转录水平的影响。方法:根据受试物在生理和离体情形下维持人基因组结构稳定的最适浓度,以含15、30、120 nmol/L的氧化型叶酸(FA)或还原型叶酸(5-MeTHF)与12 μmol/L氯化胆碱(CC)组合,以及不同浓度CC(1.5、3 μmol/L)与120 nmol/L FA组合的修饰RPMI-1640培养基,对人结肠腺癌细胞株COLO205进行20 d干预培养。以实时荧光定量PCR检测hMLH1和hMSH2 mRNA水平。结果:受试细胞株hMLH1和hMSH2 mRNA水平与FA、5-MeTHF和CC浓度呈显著负相关(P<0.01或P<0.05)。30 和120 nmol/L浓度下,5-MeTHF对上述细胞hMLH1和hMSH2转录水平的影响显著强于同等浓度的FA(P<0.01或P<0.05)。结论:FA、5-MeTHF和CC缺乏可上调结肠腺癌细胞hMLH1和hMSH2转录水平,这可能是细胞对叶酸和胆碱缺乏导致的DNA损伤和异常甲基化的应答反应。  相似文献   
7.
Intestinal microbiota is a “dynamic organ” influencing host metabolism, nutrition, physiology and immune system. Among its several interactions, the role of a phosphatidylcholine metabolite derived by gut flora activity, i.e., trimethylamine-N-oxide (TMAO), allows perceiving a novel insight in the cardiovascular risk scenario, being a strong predictor of this condition. Based on current reports, including the paper of Tang et al., we describe here: the possible role of intestinal microbiota in cardiovascular risk as well as potential interventions to reduce gut flora TMAO production by diet, probiotics and antibiotics. Finally, we highlight the possibility of evaluating, monitoring and modulating TMAO in order to use its serum levels as a marker of cardiovascular risk in the next future, when the need of controlled studies on large series will be satisfied.  相似文献   
8.
目的 采用离子色谱法测定氯化琥珀胆碱原料及注射液中的氯化胆碱和氯化琥珀酰单胆碱。方法 采用Dionex RFICTM Ionpac CS17色谱柱(4 mm×250 mm),以甲烷磺酸溶液为流动相进行梯度洗脱,流速为1.0 mL·min-1,采用抑制电导检测器进行测定。结果 氯化胆碱、氯化琥珀酰单胆碱浓度分别在18.0~562.8 μg·mL-1r=0.999 9)和14.4~449.8 μg·mL-1r=0.999 9)内线性关系良好,定量限均为0.01 μg·mL-1。原料中氯化胆碱、氯化琥珀酰单胆碱回收率分别为103.4%~105.7%和102.4%~107.1%;注射液中氯化胆碱、氯化琥珀酰单胆碱回收率分别为95.6%~100.2%和94.4%~103.5%。结论 该方法专属性强、准确、简便、快速,适用于氯化琥珀胆碱原料及制剂中的有关物质测定。  相似文献   
9.
Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end-nets and flower-spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double-labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high-resolution maps of the rat subendocardial neural plexus at the cavo-atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo-atrial junction than the mid-atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post-ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower-spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.  相似文献   
10.
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