Journal of Nutritional Biochemistry最新文献_第9页

Serum selenium, selenoprotein P and glutathione peroxidase 3 in rheumatoid, psoriatic, juvenile idiopathic arthritis, and osteoarthritis 类风湿、银屑病、幼年特发性关节炎和骨关节炎患者的血清硒、硒蛋白 P 和谷胱甘肽过氧化物酶 3。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-09 DOI: 10.1016/j.jnutbio.2024.109776

Lukas Wahl , Thilo Samson Chillon , Petra Seemann , Sarah Ohrndorf , Ragna Ochwadt , Wolfgang Becker , Lutz Schomburg , Paula Hoff

Selenoprotein P (SELENOP) controls selenium (Se) transport, and glutathione peroxidase 3 (GPx3) elicits antioxidant activity in blood. Inflammation associates with Se deficiency, but knowledge concerning selenoproteins in inflammatory rheumatic musculoskeletal diseases (iRMD) is limited. We compared three Se biomarkers in patients with rheumatoid (RA), psoriatic (PsA), and juvenile idiopathic arthritis (JIA) in comparison to osteoarthritis (OA) and healthy subjects, to improve the data base on selenoprotein expression in iRMD.

The cross-sectional study enrolled n=272 patients with RA (n=131), PsA (n=67), JIA (n=22) and OA (n=52). Serum Se was quantified by total reflection X-ray fluorescence, SELENOP by ELISA and GPx3 by an enzymatic test. Data from the EPIC trial served as reference. Impairment of daily life was assessed by the Functional Ability Questionnaire (FfbH).

Serum SELENOP and Se concentrations correlated linearly in all groups and were below the average measured in EPIC. Se concentration was not different between the patient groups. Compared to controls, SELENOP levels were low in iRMD patients. GPx3 activity was particularly low in JIA and PsA. Seropositive but not seronegative RA patients displayed a disrupted interaction between GPx3 and Se or SELENOP. SELENOP associated with the functional status measured by the FfbH, most pronounced in OA (R=0.76, P < .01).

The data indicate selenoprotein deficiency in the majority of patients with iRMD, and a positive relation of SELENOP with functional status in OA. Since increased Se supply improves selenoprotein biosynthesis, a personalized correction of diagnosed deficiency merits consideration to improve Se transport and ameliorate disease burden.

简介硒蛋白 P (SELENOP) 控制硒的运输，谷胱甘肽过氧化物酶 3 (GPx3) 在血液中激发抗氧化活性。炎症与硒缺乏有关，但有关炎症性风湿性肌肉骨骼疾病（iRMD）中硒蛋白的知识却很有限。我们比较了类风湿（RA）、银屑病（PsA）和幼年特发性关节炎（JIA）患者与骨关节炎（OA）和健康人的三种硒生物标志物，以完善 iRMD 中硒蛋白表达的数据基础：这项横断面研究共招募了272名RA（131人）、PsA（67人）、JIA（22人）和OA（52人）患者。血清中的硒通过全反射X射线荧光法进行定量，SELENOP通过酶联免疫吸附法进行定量，GPx3通过酶法测试进行定量。EPIC 试验的数据作为参考。日常生活障碍通过功能能力问卷（FfbH）进行评估：结果：在所有组别中，血清 SELENOP 和 Se 浓度呈线性相关，均低于 EPIC 试验中测得的平均值。不同患者组之间的硒浓度没有差异。与对照组相比，iRMD 患者的 SELENOP 水平较低。JIA和PsA患者的GPx3活性特别低。血清反应阳性的 RA 患者与血清反应阴性的 RA 患者之间的 GPx3 与 Se 或 SELENOP 之间的相互作用被破坏。SELENOP与FfbH测量的功能状态相关，在OA中最为明显（R=0.76，p讨论：数据表明，大多数 iRMD 患者缺乏硒蛋白，而 SELENOP 与 OA 的功能状态呈正相关。由于增加 Se 的供应可改善硒蛋白的生物合成，因此值得考虑对诊断出的缺乏症进行个性化矫正，以改善 Se 的转运并减轻疾病负担。

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引用次数: 0

Astaxanthin improves lipotoxicity, lipid peroxidation and oxidative stress in kidney of sucrose-rich diet-fed rats 虾青素可改善富含蔗糖饮食大鼠肾脏的脂毒性、脂质过氧化和氧化应激。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109779

Michelle Berenice Vega Joubert , Paola Inés Ingaramo , Pablo Collins , María Eugenia D'Alessandro

Metabolic Syndrome (MS) is a cluster of metabolic risk factors, characterized by abdominal obesity, dyslipidemia, hypertension, insulin resistance, among others. The purpose of the study was to evaluate the astaxanthin (AXT) effects extracted from freshwater crab (Dilocarcinus pagei) at the Paraná Basin on lipotoxicity, lipid peroxidation and oxidative stress in the kidney of rats fed with a sucrose-rich diet (SRD). We hypothesized that daily administration of AXT prevents kidney damage by reducing lipotoxicity, lipid peroxidation, and reactive oxygen species (ROS), and by improving antioxidant enzyme defenses and crosstalk between NrF2 and NF-ĸB transcription factors. Male Wistar rats were fed a reference diet (RD), RD+AXT, SRD and SRD+AXT (AXT daily oral dose: [10 mg/kg body weight]) for 90 days. Systolic and diastolic blood pressure, biochemical assays in serum and urine were evaluated. Renal cortex samples were taken for histological analysis, determination of triglyceride content, ROS, thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzyme activities and glutathione content (GSH). 4-HNE, NrF2, and NF-ĸB p65 expression were analyzed by immunohistochemistry. We demonstrated that daily oral supplementation of AXT to animals fed a SRD reduced systolic and diastolic blood pressure, histological renal damage, lipid accumulation, ROS and lipid peroxidation, and increased CAT and GPx activities. NrF2 protein expression in renal cortex was increased, whilst NF-ĸB p65 was reduced. AXT extracted from freshwater crabs (Dilocarcinus pagei) may be promising nutritional strategy for the prevention of renal alterations present in this model.

代谢综合征（MS）是一组代谢风险因素，以腹部肥胖、血脂异常、高血压、胰岛素抵抗等为特征。本研究旨在评估从巴拉那盆地淡水蟹（Dilocarcinus pagei）中提取的虾青素（AXT）对富含蔗糖饮食（SRD）的大鼠肾脏的脂毒性、脂质过氧化和氧化应激的影响。我们假设，每天服用 AXT 可降低脂毒性、脂质过氧化和活性氧（ROS），改善抗氧化酶的防御能力以及 NrF2 和 NF-ĸB 转录因子之间的串扰，从而防止肾脏损伤。给雄性 Wistar 大鼠喂食参考饮食 (RD)、RD+AXT、SRD 和 SRD+AXT [AXT 每日口服剂量：（10 毫克/千克体重）] 90 天。对收缩压和舒张压、血清和尿液中的生化指标进行了评估。取肾皮质样本进行组织学分析，测定甘油三酯含量、ROS、硫代巴比妥酸活性物质（TBARS）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）的酶活性和谷胱甘肽含量（GSH）。免疫组化法分析了 4-HNE、NrF2 和 NF-ĸB p65 的表达。我们的研究表明，每天口服 AXT 可降低以 SRD 为食的动物的收缩压和舒张压、组织学肾损伤、脂质积累、ROS 和脂质过氧化反应，并提高 CAT 和 GPx 活性。肾皮质中 NrF2 蛋白表达增加，NF-ĸB p65 减少。从淡水蟹（Dilocarcinus pagei）中提取的 AXT 可能是预防该模型中出现的肾脏改变的一种有前景的营养策略。

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引用次数: 0

Lycopene attenuates D-galactose-induced memory and behavioral deficits by mediating microbiota-SCFAs-gut-brain axis balance in female CD-1 mice 番茄红素通过调节雌性CD-1小鼠体内微生物群-SCFAs-肠脑轴的平衡，减轻D-半乳糖诱导的记忆和行为缺陷。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109777

Jia Wang , Yuqi Shen , Lu Li , Li Li , Juan Zhang , Mengling Li , Fubin Qiu

Aging impairs cognitive function, whereas nutritional intervention can delay aging and age-related diseases. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, the effects of LYC on memory and behavioral deficits induced by D-galactose (D-gal) treatment and the relative contribution of LYC-derived gut microbiota in these process were investigated. Results demonstrated that LYC showed effective protection on D-gal induced cognitive deficit and neuronal damage. Moreover, LYC treatment has beneficial effects on gut barrier damage, microbiota dysbiosis and levels of SCFAs in D-gal-induced subacute aging mice. Next, fecal microbiota transplantation (FMT) experiment was performed and increased SCFAs were observed in mice received stools from D-gal+LYC group when compared with D-gal-FMT group. Thus, we added SCFAs treatment served as a control group in order to evaluated whether the alterations of gut-brain axis could be attributed to LYC-reshaped gut microbiota and SCFAs. Results showed that recipient mice received SCFAs and stools from D-gal+LYC group have similar beneficial effects in improving gut and brain function, demonstrated as: improved intestinal health via elevating antioxidant enzymes contents, increasing the expressions of tight junctions proteins and protecting gut barrier, enhanced mice working memory capacity via alleviating hippocampal neurons impairment, improving synaptic function and enhancing mitochondrial function in the intestinal pseudo-aseptic mice. In conclusion, our results demonstrated that LYC-derived microbiome played a pivotal role in the regulation of cognitive functions during aging and enhanced SCFAs formation might be an important signaling molecule connecting gut microbiome and brain.

衰老会损害认知功能，而营养干预可以延缓衰老和与衰老相关的疾病。番茄红素（LYC）是一种天然类胡萝卜素，具有多种促进健康的特性，包括神经保护功能。本文研究了番茄红素对D-半乳糖（D-gal）处理诱导的记忆和行为缺陷的影响，以及番茄红素衍生的肠道微生物群在这些过程中的相对贡献。结果表明，LYC 能有效保护 D-gal 诱导的认知缺陷和神经元损伤。此外，LYC治疗对D-gal诱导的亚急性衰老小鼠的肠道屏障损伤、微生物群失调和SCFAs水平也有益处。接下来，我们进行了粪便微生物群移植（FMT）实验，结果发现与 D-gal-FMT 组相比，D-gal+LYC 组小鼠粪便中的 SCFAs 增加了。因此，我们添加了 SCFAs 处理作为对照组，以评估肠脑轴的改变是否可归因于 LYC 重组的肠道微生物群和 SCFAs。结果表明，接受 SCFAs 和 D-gal+LYC 组粪便的小鼠在改善肠道和大脑功能方面具有相似的益处，表现为：通过提高抗氧化酶含量、增加紧密连接蛋白的表达和保护肠道屏障来改善肠道健康；通过减轻海马神经元损伤、改善突触功能和增强线粒体功能来提高肠道假性变性小鼠的工作记忆能力。总之，我们的研究结果表明，LYC 衍生的微生物组在衰老过程中对认知功能的调控起着关键作用，而增强 SCFAs 的形成可能是连接肠道微生物组和大脑的重要信号分子。

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引用次数: 0

TGF-β2, EGF and FGF21 influence the suckling rat intestinal maturation TGF-β2、EGF 和 FGF21 对乳鼠肠道成熟的影响

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109778

Blanca Grases-Pintó , Paulina Torres-Castro , Mar Abril-Gil , Margarida Castell , María J. Rodríguez-Lagunas , Francisco J. Pérez-Cano , Àngels Franch

Some of the growth factors present in breast milk, such as transforming growth factor-β (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), play important roles in the development of the intestinal tract. The aim of this study was to determine the effect of a supplementation with TGF-β2, EGF and FGF21 on suckling rats intestinal maturation. For this purpose, Wistar rats were supplemented daily with TGF-β2, EGF or FGF21 throughout the suckling period. We evaluated the functionality of the intestinal epithelial barrier through an in vivo dextran permeability assay, and by a histomorphometric and immunohistochemical study. In addition, the intestinal gene expression of tight junction-associated proteins, mucins, toll-like receptors, and maturation markers was analyzed. Moreover, the intraepithelial lymphocyte (IEL) phenotypical composition was established. During the suckling period, the supplementation with TGF-β2, EGF and FGF21 showed important signs of intestinal maturation. These results suggest that these molecules, present in breast milk, play a modulatory role in the maturation of the intestinal barrier function and the IEL composition during the suckling period.

母乳中的一些生长因子，如转化生长因子-β（TGF-β）、表皮生长因子（EGF）和成纤维细胞生长因子 21（FGF21），在肠道发育中发挥着重要作用。本研究旨在确定补充 TGF-β2、EGF 和 FGF21 对乳鼠肠道成熟的影响。为此，我们在 Wistar 大鼠的整个哺乳期每天为其补充 TGF-β2、EGF 或 FGF21。我们通过体内葡聚糖渗透性试验以及组织形态学和免疫组化研究评估了肠上皮屏障的功能。此外，还分析了肠道紧密连接相关蛋白、粘蛋白、收费样受体和成熟标志物的基因表达。此外，还确定了上皮内淋巴细胞（IEL）的表型组成。在哺乳期，补充 TGF-β2、EGF 和 FGF21 可显示肠道成熟的重要迹象。这些结果表明，母乳中的这些分子对哺乳期肠道屏障功能和IEL组成的成熟起着调节作用。

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引用次数: 0

In vivo and in silico insights into the antidiabetic efficacy of EVOO and hydroxytyrosol in a rat model 对 EVOO 和羟基酪醇在大鼠模型中抗糖尿病功效的体内和硅学洞察。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109775

Mahmoud Gamal , Mohamed A. Awad , Azizeh Shadidizaji , Marwa A. Ibrahim , Magdy A. Ghoneim , Mohamad Warda

Extra virgin olive oil (EVOO) has a putative antidiabetic activity mostly attributed to its polyphenol Hydroxytyrosol. In this study, we explored the antidiabetic effects of EVOO and Hydroxytyrosol on an in vivo T2D-simulated rat model as well as in in silico study. Wistar rats were divided into four groups. The first group served as a normal control (NC), while type 2 diabetes (T2D) was induced in the remaining groups using a high-fat diet (HFD) for 12 weeks followed by a single dose of streptozotocin (STZ, 30 mg/kg). One diabetic group remained untreated (DC), while the other two groups received an 8-week treatment with either EVOO (90 g/kg of the diet) (DO) or Hydroxytyrosol (17.3 mg/kg of the diet) (DH). The DC group exhibited hallmark features of established T2D, including elevated fasting blood glucose levels, impaired glucose tolerance, increased HOMA-IR, widespread downregulation of insulin receptor expression, heightened oxidative stress, and impaired β-cell function. In contrast, treatments with EVOO and Hydroxytyrosol elicited an antidiabetic response, characterized by improved glucose tolerance, as indicated by accelerated blood glucose clearance. Systematic analysis revealed the underlying antidiabetic mechanisms: both treatments enhanced insulin receptor expression in the liver and skeletal muscles, increased adiponectin levels, and mitigated oxidative stress. Moreover, while EVOO reduced intramyocellular lipids, Hydroxytyrosol restored adipose tissue insulin sensitivity and enhanced β-cell survival. Molecular docking and dynamics confirm Hydroxytyrosol's high affinity binding to PGC-1α, IRE-1α, and PPAR-γ, particularly IRE-1α, highlighting its potential to modulate diabetic signaling pathways. Collectively, these mechanisms highlight the putative antidiabetic role of EVOO and Hydroxytyrosol. Moreover, the favorable docking scores of Hydroxytyrosol with PGC-1α, IRE-1α, and PPAR-γ support the antidiabetic potential and offer promising avenues for further research and the development of novel antidiabetic therapies.

特级初榨橄榄油（EVOO）具有抗糖尿病活性，这主要归功于其多酚羟基酪醇。在这项研究中，我们探讨了特级初榨橄榄油和羟基酪醇对模拟 T2D 大鼠模型的体内抗糖尿病作用，并进行了硅学研究。Wistar 大鼠分为四组。第一组为正常对照组（NC），其余各组均采用高脂饮食（HFD）诱导 2 型糖尿病（T2D），持续 12 周，然后单剂量注射链脲佐菌素（STZ，30 毫克/千克）。一个糖尿病组仍未接受治疗（DC），而其他两组则接受了为期八周的EVOO（90克/千克食物）（DO）或羟基酪醇（17.3毫克/千克食物）（DH）治疗。DC组表现出已确立的T2D的标志性特征，包括空腹血糖水平升高、糖耐量受损、HOMA-IR升高、胰岛素受体表达广泛下调、氧化应激增加以及β细胞功能受损。与此相反，EVOO 和羟基酪醇可引起抗糖尿病反应，其特点是葡萄糖耐量得到改善，血糖清除率加快。系统分析揭示了其潜在的抗糖尿病机制：这两种疗法都能增强肝脏和骨骼肌中胰岛素受体的表达，提高脂肪连素水平，减轻氧化应激。此外，EVOO 减少了细胞内脂类，而羟基酪醇则恢复了脂肪组织的胰岛素敏感性，并提高了 β 细胞的存活率。分子对接和动力学证实了羟基酪醇与 PGC-1α、IRE-1α 和 PPAR-γ（尤其是 IRE-1α）的高亲和力结合，突显了其调节糖尿病信号通路的潜力。总之，这些机制凸显了EVOO和羟基酪醇可能具有的抗糖尿病作用。此外，羟基酪醇与 PGC-1α、IRE-1α 和 PPAR-γ 的良好对接得分支持了其抗糖尿病的潜力，并为进一步研究和开发新型抗糖尿病疗法提供了前景广阔的途径。

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引用次数: 0

Chenodeoxycholic acid fortified diet drives ovarian steroidogenesis to improve embryo implantation through enhancing uterine receptivity via progesterone receptor signaling pathway in rats 陈去氧胆酸强化膳食通过黄体酮受体信号通路增强大鼠子宫的受孕能力，从而促进卵巢类固醇生成以改善胚胎着床。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-09-28 DOI: 10.1016/j.jnutbio.2024.109774

Meixia Chen , Xiaoyi Zhao , Zhuo Chang , Hui Liu , Longlong Zhu , Sixin Wang , Dongyang Zhang , Jing Wang

Infertility is a worldwide reproductive health problem influenced by the embryo implantation efficiency. We previously revealed that dietary chenodeoxycholic acid (CDCA) positively influence the early embryo implantation. But how CDCA regulate embryo implantation is largely unexplored. Herein, we investigated the mechanism behind CDCA's regulation on embryo implantation in rats. Results showed that CDCA promoted uterine receptivity, leading to increased number of implantation sites. Mechanistically, CDCA reshaped maternal amino acid metabolism and enhanced serum progesterone levels. CDCA enhanced ovarian progesterone synthesis by improving steroidogenesis-related protein (StAR and CYP11A1) expression via Takeda G-protein-coupled receptor 5. Elevated progesterone exaggerated uterine progesterone but weakened the estradiol signaling in the CDCA group, contributing to better uterine receptive for embryo implantation. Additionally, elevated transcription repressor Stat5b induced the down-regulation of progesterone-metabolizing enzyme 20-hydroxysteroid dehydrogenase 20α-HSD, complementally explained uterine progesterone signaling enhancement. Overall, our data revealed that CDCA drove ovarian steroidogenesis to improve embryo implantation through enhancing uterine receptivity via progesterone receptor pathway in rats. Therefore, CDCA diet may be a potential favorable nutritional strategy for infertility and pregnancy management.

不孕症是受胚胎植入效率影响的世界性生殖健康问题。我们曾发现，膳食中的酚去氧胆酸（CDCA）对早期胚胎着床有积极影响。但 CDCA 是如何调控胚胎着床的，目前尚无定论。在此，我们研究了 CDCA 调节大鼠胚胎着床的机制。结果表明，CDCA能促进子宫的接受能力，从而增加胚胎着床点的数量。从机制上看，CDCA重塑了母体氨基酸代谢，提高了血清孕酮水平。CDCA 通过武田 G 蛋白偶联受体 5 改善类固醇生成相关蛋白（StAR 和 CYP11A1）的表达，从而促进卵巢孕酮的合成。在 CDCA 组中，孕酮升高使子宫孕酮增加，但削弱了雌二醇信号传导，从而使子宫更容易接受胚胎着床。此外，转录抑制因子Stat5b的升高诱导了孕酮代谢酶20-羟基类固醇脱氢酶20α-HSD的下调，补充解释了子宫孕酮信号增强的原因。总之，我们的数据显示，CDCA 通过孕酮受体途径增强大鼠子宫的接受能力，从而促进卵巢类固醇生成，改善胚胎着床。因此，CDCA饮食可能是治疗不孕症和妊娠的潜在有利营养策略。

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引用次数: 0

Association of serum n-3 and n-6 docosapentaenoic acids with cognitive performance in elderly adults: National Health and Nutrition Examination Survey 2011–2014 血清 n-3 和 n-6 二十二碳五烯酸与老年人认知能力的关系：2011-2014 年全国健康与营养调查。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-09-25 DOI: 10.1016/j.jnutbio.2024.109773

Guoxin Lin , Juan Tang , Youjie Zeng , Li Zhang , Wen Ouyang , Yongzhong Tang

Limited information exists on the influence of docosapentaenoic acid (DPA) on cognitive function. We investigated the association between serum n-3 and n-6 DPAs and cognitive performance in an elderly population from the National Health and Nutrition Examination Survey, 2011–2014. Restricted cubic spline and logistic regression analyses were utilized. A total of 1,366 older participants were included. Elevated proportions of DPA(n3) in total serum fatty acids were slightly associated with higher DSST scores (OR 0.61, 95% CI (0.38–0.97)), and higher proportions of DPA(n6) in total serum fatty acids were significantly associated with lower scores on different cognitive tests (CERAD (1.64, 1.02-2.65), AFT (2.31, 1.43- 3.75), DSST (3.21, 1.98-5.22) and global cognition (2.85, 1.74–4.66)). After multivariable adjustment, DPA(n3) exhibited no association with cognitive performance, whereas DPA(n6) remained correlated with AFT (1.98, 1.13–3.48), DSST (2.63, 1.43–4.82) and global cognition (2.15, 1.19–3.90). In stratified analyses, higher levels of DPA(n3) were associated with better performance in CERAD among participants aged ≥70, in DSST among those without diabetes and in global cognition among people with lower incomes. Increased DPA(n6) levels were associated with worse performance in AFT and DSST among those aged 60–70 and in all cognitive tests among those with better incomes. In conclusions, elevated levels of serum DPA(n3) may be beneficial for cognitive performance among elderly adults, especially in those over 70 years, with lower incomes and without diabetes. Serum n-6 DPA might be negatively associated with cognitive function, and this association is more pronounced among those who aged 60–70 with higher incomes.

有关二十二碳五烯酸（DPA）对认知功能影响的信息十分有限。我们研究了 2011-2014 年全国健康与营养调查中老年人群血清中 n-3 和 n-6 DPA 与认知能力之间的关系。我们采用了限制性三次样条分析和逻辑回归分析。共纳入 1366 名老年参与者。血清总脂肪酸中 DPA(n3) 比例的升高与较高的 DSST 分数略有关联（OR 0.61，95% CI (0.38-0.97)），而较高的 DPA(n3) 比例与较高的 DSST 分数略有关联（OR 0.61，95% CI (0.38-0.97)血清总脂肪酸中 DPA(n6) 比例较高与不同认知测试（CERAD（1.64，1.02-2.65）、AFT（2.31，1.43-3.75）、DSST（3.21，1.98-5.22）和总体认知（2.85，1.74-4.66））得分较低显著相关。）经多变量调整后，DPA(n3)与认知表现没有关联，而DPA(n6)仍与AFT（1.98，1.13-3.48）、DSST（2.63，1.43-4.82）和总体认知（2.15，1.19-3.90）相关。在分层分析中，DPA(n3)水平越高，年龄≥70岁的参与者在CERAD中的表现越好，无糖尿病者在DSST中的表现越好，而收入较低者在总体认知中的表现越好。在 60-70 岁的人群中，DPA(n6) 水平升高与 AFT 和 DSST 成绩下降有关，而在收入较高的人群中，与所有认知测试成绩下降有关。总之，血清中 DPA(n3) 水平的升高可能对老年人的认知能力有益，尤其是对 70 岁以上、收入较低且无糖尿病的老年人。血清 n-6 DPA 可能与认知功能呈负相关，这种关联在收入较高的 60-70 岁老年人中更为明显。

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引用次数: 0

A natural small molecule pinocembrin resists high-fat diet-induced obesity through GPR120-ERK1/2 pathway 天然小分子 pinocembrin 可通过 GPR120-ERK1/2 通路抵抗高脂饮食诱发的肥胖症。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-09-21 DOI: 10.1016/j.jnutbio.2024.109772

Ziyi Zhang, Zhaozhao He, Xinyi Wang, Boyu Huang, Wanrong Zhang, Yiwen Sha, Weijun Pang

Obesity is a widely concerned health problem. Mobilizing white adipose tissue and reducing fat synthesis are considered as effective strategies in the treatment of obesity. Here, using Connectivity Map (CMap) approach, we identified the pinocembrin (PB), a natural flavonoid primarily found in propolis, as a potential anti-obesity drug. Therefore, high-fat-diet (HFD) mice were randomly divided into two groups and fed a HFD or HFD with PB in this study. In vivo experiments showed that supplementation of PB reduced the body weight gain and ameliorated insulin resistance in HFD-induced mice. More importantly, PB did not cause side effect through detecting the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine (CRE) and blood urea nitrogen (BUN) in serum of mice. Additionally, PB reduced expansion of white adipose tissue with upregulation of genes related lipolysis and downregulation of genes related lipogenesis. Furthermore, in vitro experiments revealed that PB treatment dose-dependently inhibited lipid droplet formation with upregulation of genes related lipolysis and downregulation of genes related lipogenesis. Molecular docking analysis combined with cellular thermal shift assay (CETSA) suggested that PB has a high affinity to the G protein-coupled receptor 120 (GPR120). Meanwhile, we confirmed that PB efficiently inhibited adipogenic differentiation of preadipocytes by directly binding to GPR120 and subsequently activating the downstream phosphorylation extracellular regulated kinase 1/2 (ERK1/2). Collectively, PB exerted anti-obesity effect through GPR120-ERK1/2 signaling pathway, providing a novel and promising natural drug for the treatment of obesity.

肥胖症是一个广受关注的健康问题。调动白色脂肪组织和减少脂肪合成被认为是治疗肥胖症的有效策略。在此，我们利用连接图（CMap）方法，将主要存在于蜂胶中的天然类黄酮--pinocembrin（PB）确定为一种潜在的抗肥胖药物。因此，本研究将高脂饮食（HFD）小鼠随机分为两组，分别喂食高脂饮食或喂食含 PB 的高脂饮食。体内实验表明，补充 PB 可减少高脂饮食诱导的小鼠体重增加，并改善胰岛素抵抗。更重要的是，通过检测小鼠血清中丙氨酸转氨酶（ALT）、天门冬氨酸转氨酶（AST）、肌酐（CRE）和血尿素氮（BUN）的水平，PB 不会产生副作用。此外，PB 还能减少白色脂肪组织的扩张，上调与脂肪分解相关的基因，下调与脂肪生成相关的基因。此外，体外实验显示，PB 可抑制脂滴的形成，上调与脂肪分解相关的基因，下调与脂肪生成相关的基因。分子对接分析结合细胞热转移试验（CETSA）表明，PB 与 G 蛋白偶联受体 120（GPR120）具有很高的亲和力。同时，我们证实了 PB 通过直接与 GPR120 结合并激活下游磷酸化细胞外调控激酶 1/2（ERK1/2），从而有效抑制了前脂肪细胞的成脂分化。总之，PB通过GPR120-ERK1/2信号通路发挥抗肥胖作用，为治疗肥胖症提供了一种新型的、有前景的天然药物。

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引用次数: 0

The flavonoid hydroxygenkwanin reduces inflammation and neointimal formation 黄酮类羟基黄酮能减少炎症和新内膜的形成。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-09-18 DOI: 10.1016/j.jnutbio.2024.109771

Pin-Yu Chen , Mao-Shin Lin , Chin-Chuan Chen , Yann-Lii Leu , Shu-Huei Wang

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play crucial roles in neointimal hyperplasia and restenosis progression in response to stimulation with various inflammatory cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and tumour necrosis factor-α (TNF-α). Hydroxygenkwanin (HGK) exerts remarkable anti-inflammatory, antitumour, antiproliferative and antimigratory effects. The aim of the study was to elucidate the therapeutic effect and regulatory mechanism of HGK on neointimal hyperplasia. The results showed that HGK inhibited the abnormal proliferation, migration, and inflammation of PDGF-BB- or TNF-α-treated VSMCs through regulation of the PDK1/AKT/mTOR pathway. In addition, HGK promoted circulating endothelial progenitor cell (EPC) chemotaxis. In an in vivo assay, HGK dramatically enhanced re-endothelization and reduced neointimal hyperplasia after femoral artery denudation with a guide wire in mice. These results suggest that HGK can serve as a therapeutic target drug or a functional food supplement for the treatment of restenosis.

背景和目的：血管平滑肌细胞（VSMC）在血小板衍生生长因子-BB（PDGF-BB）和肿瘤坏死因子-α（TNF-α）等各种炎症细胞因子的刺激下，出现异常增殖和迁移，在新内膜增生和再狭窄进展中起着至关重要的作用。羟基花青素（HGK）具有显著的抗炎、抗肿瘤、抗增殖和抗移行作用。本研究旨在阐明 HGK 对新内膜增生的治疗作用和调控机制：方法：在体外进行 Western 印迹分析、细胞周期分析、MTT、BrdU 结合、伤口愈合和粘附试验，以确定 HGK 对 PDGF-BB 或 TNF-α 处理的 VSMC 的治疗效果。此外，还进行了对接分析和细胞热转移试验，以阐明 HGK 调节作用的机制。对断裂的股动脉进行组织学和免疫组化染色，以阐明HGK在体内的治疗效果：结果和结论：HGK通过调节PDK1/AKT/mTOR通路，抑制了PDGF-BB或TNF-α处理的VSMC的异常增殖、迁移和炎症反应。此外，HGK 还能促进循环内皮祖细胞（EPC）的趋化。在体内试验中，HGK 显著增强了小鼠股动脉导丝剥脱后的再内皮化并减少了新内膜增生。这些结果表明，HGK 可作为治疗再狭窄的靶向药物或功能性食品补充剂。

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引用次数: 0

Refining the Rab7-V1G1 axis to mitigate iron deposition: Protective effects of quercetin in alcoholic liver disease 完善 Rab7-V1G1 轴以减轻铁沉积：槲皮素对酒精性肝病的保护作用。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-09-14 DOI: 10.1016/j.jnutbio.2024.109767

Hongkun Lin , Xiaoping Guo , Jingjing Liu , Li Chen , Huimin Chen , Ying Zhao , Hongxia Li , Shuang Rong , Ping Yao

Iron overload is a common feature of alcoholic liver disease (ALD) and contributes significantly to disease progression. Quercetin, a flavonoid known for its iron-chelating properties, has emerged as a potential protective compound against ALD. However, research on quercetin's regulatory effects on iron levels in ALD is limited. To address this, we conducted a study using male C57BL/6J mice were subjected to a Lieber De Carli liquid diet containing ethanol (28% energy replacement) with or without quercetin supplementation (100 mg/kg.BW) for 12 weeks. Additionally, HepG2 cells, after transfection with the CYP2E1 plasmid, were incubated with ethanol and/or quercetin. Our findings revealed that ethanol consumption led to iron overload in both hepatocytes and lysosomes. Interestingly, despite the increase in iron levels, cells exhibited impaired iron utilization, disrupting normal iron metabolism. Further analysis identified a potential mechanism involving the Rab7-V1G1 (V-ATPase subunit) axis. Inhibition of V-ATPase by Concanamycin A caused elevated ROS levels, impaired lysosomal and mitochondria function, and increased expression of HIF1α and IRP2. Ultimately, this disruption in cellular processes led to iron overload and mitochondrial iron deficiency. Quercetin supplementation mitigated ethanol-induced hepatocyte damage by reversing iron overload through modulation of the Rab7-V1G1 axis and improving the interaction between lysosomes and mitochondria. In conclusion, this study elucidates a novel pathophysiological mechanism by which quercetin protects against ALD through its regulation of iron homeostasis.

铁超载是酒精性肝病（ALD）的一个常见特征，对疾病的进展起着重要作用。槲皮素是一种黄酮类化合物，以其螯合铁的特性而闻名，它已成为一种潜在的防止酒精性肝病的保护性化合物。然而，有关槲皮素对 ALD 中铁水平的调节作用的研究还很有限。为了解决这个问题，我们用雄性 C57BL/6J 小鼠进行了一项研究，让它们食用含有乙醇（28% 的能量替代）的 Lieber De Carli 液体饮食，同时补充或不补充槲皮素（100 mg/kg.BW），持续 12 周。此外，用 CYP2E1 质粒转染 HepG2 细胞后，与乙醇和/或槲皮素一起培养。我们的研究结果表明，服用乙醇会导致肝细胞和溶酶体中铁超载。有趣的是，尽管铁含量增加了，但细胞对铁的利用却出现了障碍，破坏了正常的铁代谢。进一步分析发现了涉及 Rab7-V1G1（V-ATP 酶亚基）轴的潜在机制。康那霉素 A 抑制 V-ATP 酶会导致 ROS 水平升高、溶酶体和线粒体功能受损以及 HIF1α 和 IRP2 表达增加。细胞过程的这种破坏最终导致铁超载和线粒体缺铁。补充槲皮素可通过调节 Rab7-V1G1 轴和改善溶酶体与线粒体之间的相互作用来逆转铁超载，从而减轻乙醇诱导的肝细胞损伤。总之，本研究阐明了槲皮素通过调节铁稳态防止 ALD 的一种新的病理生理机制。

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引用次数: 0