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Dietary curcumin supplementation attenuates hepatic damage and function abnormality in a chronic corticosterone-induced stress model in broilers 在慢性皮质酮诱导的肉鸡应激模型中,补充姜黄素能减轻肝损伤和功能异常。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-19 DOI: 10.1016/j.jsbmb.2024.106579
Xuemei Shan , Xingyu Xu , Lijun Wang , Yao Lu , Xinyu Chen , Fei Li , Min Du , Hua Xing , Shifeng Pan

Chronic stress refers to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated blood contents of ACTH and corticosterone (CORT), exhibiting significant adverse effects on health outcomes. Currently, natural polyphenol compounds are increasingly being explored as potential therapeutic agents and have been considered as a treatment option for a variety of stress-induced diseases. Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong health-beneficial properties. The study aimed to assess the potential protective effects of CUR on hepatic oxidative stress damage and abnormal lipid deposition in a chronic CORT-induced stress (CCIS) model in broilers. One hundred and twenty experimental broilers were randomly divided into 1) control group (CON), 2) CUR group (200 mg/kg feed), 3) CORT group (4 mg/kg BW CORT) and 4) CORT+CUR group (200 mg/kg feed plus 4 mg/kg BW CORT). The liver histology, glycolipid metabolism and oxidative stress were determined. In addition, qPCR was performed to identify shifts in genes expression. Compared with CON group, broilers under CCIS showed a decreased body weight, body weight gain and average daily gain, while dietary CUR significantly reversed these adverse effects. Furthermore, the plasma contents of TCH, TG, HDL-C, LDL-C, TP, GLB and AST were all significantly increased in CCIS broilers, while dietary CUR obviously alleviated the increase of TCH, HDL-C, LDL-C and AST, and relieved the hepatic lipid deposition disorder and liver injury. Moreover, CCIS significantly increased the contents of MDA in both liver and plasma, and decreased the content of plasma SOD, while CUR obviously reversed these changes, showing reduced oxidative stress damage. Finally, the mRNA expressions of FAS, ACC, SCD and the protein level of PPAR-γ were significantly increased, meanwhile the mRNA expression of lipolytic genes ACOX1, ATGL and CPT as well as two major intracellular antioxidant enzymes SOD1 and GPX1 were obviously decreased, while CUR effectively reversed these effects. These results showed that dietary CUR effectively alleviated CCIS-induced body weight loss, hepatic oxidative damage and lipid deposition disorder, suggesting the possible therapeutic effectiveness of CUR against hepatic damage and function abnormality caused by CCIS.

慢性压力是指下丘脑-垂体-肾上腺(HPA)轴被激活,血液中的促肾上腺皮质激素(ACTH)和皮质酮(CORT)含量升高,对健康产生显著的不利影响。目前,天然多酚化合物正被越来越多地开发为潜在的治疗药物,并被认为是治疗各种应激性疾病的一种选择。姜黄素(CUR)是姜黄(Zingiberacea)根茎中的主要物质,具有很强的保健功效。本研究旨在评估 CUR 在慢性 CORT 诱导应激(CCIS)模型中对肉鸡肝脏氧化应激损伤和异常脂质沉积的潜在保护作用。将 120 只实验肉鸡随机分为:1)对照组(CON);2)CUR 组(200 毫克/千克饲料);3)CORT 组(4 毫克/千克体重 CORT);4)CORT+CUR 组(200 毫克/千克饲料加 4 毫克/千克体重 CORT)。对肝组织学、糖脂代谢和氧化应激进行了测定。此外,还进行了 qPCR 分析,以确定基因表达的变化。与CON组相比,CCIS组肉鸡的体重、增重和平均日增重均有所下降,而日粮CUR则显著逆转了这些不良影响。此外,CCIS组肉鸡血浆中TCH、TG、HDL-C、LDL-C、TP、GLB和AST含量均显著升高,而日粮CUR明显缓解了TCH、HDL-C、LDL-C和AST的升高,缓解了肝脏脂质沉积障碍和肝损伤。此外,CCIS明显增加了肝脏和血浆中MDA的含量,降低了血浆中SOD的含量,而CUR明显逆转了这些变化,表明氧化应激损伤减轻。最后,FAS、ACC、SCD 的 mRNA 表达量和 PPAR-γ 蛋白水平明显升高,同时脂肪分解基因 ACOX1、ATGL 和 CPT 以及细胞内两种主要抗氧化酶 SOD1 和 GPX1 的 mRNA 表达量明显降低,而 CUR 能有效逆转这些影响。这些结果表明,膳食CUR能有效缓解CCIS引起的体重下降、肝脏氧化损伤和脂质沉积紊乱,表明CUR对CCIS引起的肝脏损伤和功能异常可能具有治疗作用。
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引用次数: 0
Exploring neuron-specific steroid synthesis and DHEAS therapy in Alzheimer's disease 探索阿尔茨海默病的神经元特异性类固醇合成和 DHEAS 治疗。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-15 DOI: 10.1016/j.jsbmb.2024.106585
Hong-Yi Lin , Yin-Hsun Feng , Tzu-Jen Kao , Hsien-Chung Chen , Guan-Yuan Chen , Chiung-Yuan Ko , Tsung-I. Hsu

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Recent studies have suggested a potential role for steroid synthesis in AD pathology. This study investigated the co-localization of steroidogenic enzymes in neuronal cells, changes in enzyme expression in an AD mouse model, and steroid expressions in human AD samples. Additionally, we conducted a steroidomic metabolomics analysis and evaluated the effects of dehydroepiandrosterone sulfate (DHEAS) treatment in an AD mouse model. Immunofluorescence analysis revealed significant co-localization of cytochrome P450 family 17 subfamily A member 1 (CYP17A1) and steroidogenic acute regulatory protein (StAR) proteins with α-synuclein in presynaptic neurons, suggesting active steroid synthesis in these cells. Conversely, such co-localization was absent in astrocytes. In the AD mouse model, a marked decrease in the expression of steroidogenic enzymes (Cyp11a1, Cyp17a1, Star) was observed, especially in areas with amyloid beta plaque accumulation. Human AD and MS brain tissues showed similar reductions in StAR and CYP17A1 expressions. Steroidomic analysis indicated a downregulation of key steroids in the serum of AD patients. DHEAS treatment in AD mice resulted in improved cognitive function and reduced Aβ accumulation. Our findings indicate a neuron-specific pathway for steroid synthesis, potentially playing a crucial role in AD pathology. The reduction in steroidogenic enzymes and key steroids in AD models and human samples suggests that impaired steroid synthesis is a feature of neurodegenerative diseases. The therapeutic potential of targeting steroid synthesis pathways, as indicated by the positive effects of DHEAS treatment, warrants further investigation.

阿尔茨海默病(AD)是一种神经退行性疾病,以认知能力下降和记忆力减退为特征。最近的研究表明,类固醇合成在阿尔茨海默病病理学中可能发挥作用。本研究调查了类固醇生成酶在神经细胞中的共定位、AD 小鼠模型中酶表达的变化以及人类 AD 样本中类固醇的表达。此外,我们还进行了类固醇组代谢组学分析,并评估了硫酸脱氢表雄酮(DHEAS)治疗对AD小鼠模型的影响。免疫荧光分析显示,突触前神经元中的细胞色素P450家族17亚家族A成员1(CYP17A1)和类固醇生成急性调节蛋白(StAR)蛋白与α-突触核蛋白显著共定位,表明这些细胞中类固醇合成活跃。相反,在星形胶质细胞中却没有这种共定位现象。在AD小鼠模型中,观察到类固醇生成酶(Cyp11a1、Cyp17a1、Star)的表达明显减少,尤其是在淀粉样β斑块堆积的区域。人类AD和多发性硬化症脑组织中StAR和CYP17A1的表达也出现了类似的减少。类固醇组学分析表明,AD 患者血清中的主要类固醇出现下调。对AD小鼠进行DHEAS治疗可改善认知功能并减少Aβ的积累。我们的研究结果表明,类固醇合成的神经元特异性途径可能在AD病理学中发挥关键作用。AD 模型和人体样本中类固醇生成酶和关键类固醇的减少表明,类固醇合成受损是神经退行性疾病的一个特征。DHEAS 治疗的积极效果表明,针对类固醇合成途径的治疗潜力值得进一步研究。
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引用次数: 0
Effects of a supraphysiological dose of testosterone cypionate on salivary gland function in adult male Wistar rats 超生理剂量的环戊丙酸睾酮对成年雄性 Wistar 大鼠唾液腺功能的影响
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-14 DOI: 10.1016/j.jsbmb.2024.106587
Larissa Victorino Sampaio , Heloisa Rodrigues dos Santos Landim , Arieli Raymundo Vazão , Gabriela Alice Fiais , Rayara Nogueira de Freitas , Allice Santos Cruz Veras , Rita Cassia Menegatti Dornelles , Walid D. Fakhouri , Rafael Rodrigues Lima , Giovana Rampazzo Teixeira , Antonio Hernandes Chaves-Neto

The abusive use of anabolic androgenic steroids has become a serious health problem worldwide, but its effects on oral health are still poorly understood. Therefore, the objective of this study was to evaluate the effects of a supraphysiological dose of testosterone cypionate (TC) on salivary biochemical, histomorphology, immunohistochemistry, and redox state parameters of parotid and submandibular glands. Twenty male Wistar rats, 12 weeks old, were divided into two groups (n=10/group): a control group and TC group, which received a dose of 20 mg/kg, once a week, for 6 weeks. Post treatment, the saliva and glands were collected. A supraphysiological dose of TC increased plasma and salivary testosterone concentrations. Although TC did not alter salivary flow, pH, and buffering capacity, the treatment increased the salivary secretion of total protein and reduced amylase, calcium, phosphate, and potassium. TC reduced the connective tissue area in the parotid gland and acinar area of the submandibular gland, while increasing the granular convoluted tubule area in the submandibular gland. Proliferating cell nuclear antigen was higher in the acinar cells of the submandibular glands from the TC group. Moreover, TC increased concentrations of total oxidant capacity and damaged lipids in both salivary glands, while total antioxidant activity and uric acid were lower in the submandibular gland, and reduced glutathione was higher in both glands. Superoxide dismutase, catalase, and glutathione peroxidase activities were higher in the parotid gland, while only glutathione peroxidase activity was lower in the submandibular gland of the TC group. In conclusion, TC abuse may be a potential factor for dysfunction of the parotid and submandibular glands, becoming a risk factor for the oral and systemic health of users.

滥用合成代谢雄性类固醇已成为全球严重的健康问题,但人们对其对口腔健康的影响仍知之甚少。因此,本研究旨在评估超生理剂量的环戊丙酸睾酮(TC)对腮腺和颌下腺唾液生化、组织形态学、免疫组化和氧化还原状态参数的影响。将 20 只 12 周大的雄性 Wistar 大鼠分为两组(n=10/组):对照组和 TC 组,对照组每周一次,每次 20 毫克/千克,连续 6 周。治疗后,收集唾液和腺体。超生理剂量的睾酮增加了血浆和唾液中的睾酮浓度。虽然 TC 没有改变唾液流量、pH 值和缓冲能力,但治疗增加了唾液中总蛋白质的分泌,降低了淀粉酶、钙、磷酸盐和钾的含量。TC减少了腮腺的结缔组织面积和颌下腺的针状腺面积,但增加了颌下腺的颗粒状曲小管面积。TC组颌下腺的针状细胞中增殖细胞核抗原含量较高。此外,TC 还增加了两种唾液腺的总氧化能力和受损脂质的浓度,而总抗氧化活性和尿酸在下颌下腺中较低,还原型谷胱甘肽在两种唾液腺中均较高。腮腺的超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性较高,而 TC 组的颌下腺中只有谷胱甘肽过氧化物酶活性较低。总之,滥用三氯乙酸可能是导致腮腺和颌下腺功能失调的潜在因素,成为影响使用者口腔和全身健康的危险因素。
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引用次数: 0
Triclosan affects steroidogenesis in mouse primary astrocytes in vitro with engagement of Sirtuin 1 and 3 三氯生通过参与 Sirtuin 1 和 3 影响体外小鼠原发性星形胶质细胞的类固醇生成。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-14 DOI: 10.1016/j.jsbmb.2024.106586
Konrad A. Szychowski , Bartosz Skóra

Triclosan (TCS) is a widely used antimicrobial, antifungal, and antiviral agent. To date, it has been reported that TCS can enter the human body and disrupt hormonal homeostasis. Therefore, the aim of our paper was to evaluate the impact of TCS on astrocytes, i.e. a crucial population of cells responsible for steroid hormone production. Our data showed that, in mouse primary astrocyte cultures, TCS can act as an endocrine disrupting chemical through destabilization of the production or secretion of progesterone (P4), testosterone (T), and estradiol (E2). TCS affects the mRNA expression of enzymes involved in neurosteroidogenesis, such as Cyp17a1, 17β-Hsd, and Cyp19a1. Our data showed that a partial PPARγ agonist (honokiol) prevented changes in Cyp17a1 mRNA expression caused by TCS. Similarly, honokiol inhibited TCS-stimulated P4 release. However, rosiglitazone (classic PPARγ agonist) or GW9662 (PPARγ antagonist) had a much stronger effect. Therefore, we believe that the changes observed in the P4, T, and E2 levels are a result of dysregulation of the activity of the aforementioned enzymes, whose expression can be affected by TCS through a Pparγ-dependent pathway. TCS was found to decrease the aryl hydrocarbon receptor (AhR) and Sirtuin 3 protein levels, which may be the result of the activation of the these proteins. Since our study showed dysregulation of the production or secretion of neurosteroids in astrocytes, it can be concluded that TCS reaching the brain may contribute to the development of neurodegenerative diseases in which an abnormal amount of neurosteroids is observed.

三氯生(TCS)是一种广泛使用的抗菌剂、抗真菌剂和抗病毒剂。迄今为止,已有报道称三氯生可进入人体并破坏荷尔蒙平衡。因此,我们的论文旨在评估三氯氢硅对星形胶质细胞(即负责类固醇激素分泌的重要细胞群)的影响。我们的数据显示,在小鼠原代星形胶质细胞培养物中,三氯氢硅可通过破坏孕酮(P4)、睾酮(T)和雌二醇(E2)的产生或分泌的稳定性,起到干扰内分泌的化学物质的作用。TCS会影响参与神经类固醇生成的酶的mRNA表达,如Cyp17a1、17β-Hsd和Cyp19a1。我们的数据显示,PPARγ部分激动剂(honokiol)可阻止TCS引起的Cyp17a1 mRNA表达变化。同样,honokiol 也抑制了 TCS 刺激的 P4 释放。然而,罗格列酮(典型的 PPARγ 激动剂)或 GW9662(PPARγ 拮抗剂)的作用更强。因此,我们认为在 P4、T 和 E2 水平上观察到的变化是上述酶活性失调的结果,而 TCS 可通过 Pparγ 依赖性途径影响这些酶的表达。研究发现,TCS 可降低芳基烃受体(AhR)和 Sirtuin 3 蛋白水平,这可能是这些蛋白被激活的结果。由于我们的研究显示星形胶质细胞中神经类固醇的产生或分泌失调,因此可以得出结论,三氯生化碳酸盐进入大脑可能会导致神经类固醇含量异常的神经退行性疾病的发生。
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引用次数: 0
Associations between serum metabolites and female cancers: A bidirectional two-sample mendelian randomization study 血清代谢物与女性癌症之间的关系:双向双样本泯灭随机研究
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-13 DOI: 10.1016/j.jsbmb.2024.106584
ZheXu Cao, XiongZhi Long, LiQin Yuan

Female cancers, especially breast, ovarian, cervical, and endometrial cancers, constitute a major threat to women's health worldwide. In view of the complex genetic background of cancers cannot be fully explained with current genetic information, we used a bidirectional two-sample mendelian randomization approach to explore the causal associations between serum metabolites and four major female cancers—breast, ovarian, cervical, and endometrial cancers. We analyzed the metabolites dataset from the Canadian Longitudinal Study of Aging and cancer datasets from the 10th round of the Finngen project. Replication analyses was performed with Cancer Association Consortium and Leo’s studies. Instrumental variables were analyzed using methods including the Wald ratio, inverse-variance weighted, MR-Egger, and weighted median. To ensure robustness, sensitivity analyses were performed using Cochrane’s Q, Egger’s intercept, MR-PRESSO, and leave-one-out methods. After meticulous analysis, we obtained levels of 3-hydroxyoleoylcarnitine, hexadecanedioate, tetradecanedioate, and carnitine C14 with robust causal associations with breast cancer, levels of 5alpha-androstan-3alpha,17beta-diol monosulfate (1), androstenediol (3beta,17beta) monosulfate (1), androsterone sulfate, and 5alpha-androstan-3beta,17beta-diol disulfate causal associations with endometrial cancer. The reverse analysis showed that breast, ovarian, and endometrial cancer and survival of breast and ovarian cancer were found to have causal relationships with 8, 5, 2, 6, and 3 metabolites, respectively. These insights underscore the potential roles of specific metabolites in the etiology of female cancers, providing new biomarkers for early detection, risk stratification, and disease progression monitoring. Further research could elucidate how these metabolites influence specific pathways in cancer development, offering theoretical foundations for prevention and treatment strategies.

女性癌症,尤其是乳腺癌、卵巢癌、宫颈癌和子宫内膜癌,是全球女性健康的主要威胁。鉴于目前的遗传信息无法完全解释癌症复杂的遗传背景,我们采用了双向双样本亡羊补牢随机方法来探讨血清代谢物与四种主要女性癌症--乳腺癌、卵巢癌、宫颈癌和子宫内膜癌之间的因果关系。我们分析了加拿大老龄化纵向研究的代谢物数据集和第十轮芬根项目的癌症数据集。与癌症协会联合会和利奥的研究进行了重复分析。工具变量的分析方法包括沃尔德比率、逆方差加权、MR-Egger 和加权中位数。为确保稳健性,我们使用 Cochrane's Q、Egger's 截距、MR-PRESSO 和 leave-one-out 方法进行了敏感性分析。经过细致的分析,我们得到了与乳腺癌有密切因果关系的 3-hydroxyoleoylcarnitine、十六碳二酸酯、十四碳二酸酯和肉碱 C14 的水平,以及 5alpha androstan-3alpha、17beta-二醇单硫酸盐 (1)、雄二醇 (3beta,17beta) 单硫酸盐 (1)、雄甾酮硫酸盐和 5α-雄甾烷-3beta,17beta-二醇二硫酸盐的水平与子宫内膜癌存在因果关系。反向分析表明,乳腺癌、卵巢癌和子宫内膜癌以及乳腺癌和卵巢癌的存活率分别与 8、5、2、6 和 3 种代谢物存在因果关系。这些发现强调了特定代谢物在女性癌症病因中的潜在作用,为早期检测、风险分层和疾病进展监测提供了新的生物标志物。进一步的研究可以阐明这些代谢物如何影响癌症发展的特定途径,为预防和治疗策略提供理论基础。
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引用次数: 0
The anti-aromatase and anti-estrogenic activity of plant products in the treatment of estrogen receptor-positive breast cancer 植物产品在治疗雌激素受体阳性乳腺癌中的抗芳香化酶和抗雌激素活性。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-10 DOI: 10.1016/j.jsbmb.2024.106581

Despite being the focal point of decades of research, female breast cancer (BC) continues to be one of the most lethal cancers in the world. Given that 80 % of all diagnosed BC cases are estrogen receptor-positive (ER+) with carcinogenesis driven by estrogen-ERα signalling, current standard of care (SOC) hormone therapies are geared towards modulating the function and expression levels of estrogen and its receptors, ERα and ERβ. Currently, aromatase inhibitors (AIs), selective ER modulators (SERMs) and selective ER degraders (SERDs) are clinically prescribed for the management and treatment of ER+ BC, with the anti-aromatase activity of AIs abrogating estrogen biosynthesis, while the anti-estrogenic SERMs and SERDs antagonise and degrade the ER, respectively. The use of SOC hormone therapies is, however, significantly hampered by the onset of severe side-effects and the development of resistance. Given that numerous studies have reported on the beneficial effects of plant compounds and/or extracts and the multiple pathways through which they target ER+ breast carcinogenesis, recent research has focused on the use of dietary chemopreventive agents for BC management. When combined with SOC treatments, several of these plant components and/or extracts have demonstrated improved efficacy and/or synergistic impact. Moreover, despite a lack of in vivo investigations, plant products are generally reported to have a lower side-effect profile than SOC therapies and are therefore thought to be a safer therapeutic choice. Thus, the current review summarizes the findings from the last five years regarding the anti-aromatase and anti-estrogenic activity of plant products, as well as their synergistic anti-ER+ BC effects in combination with SOC therapies.

尽管女性乳腺癌(BC)是几十年来研究的重点,但它仍然是世界上致死率最高的癌症之一。在所有确诊的乳腺癌病例中,80%为雌激素受体阳性(ER+),癌变由雌激素-ERα信号驱动,因此目前的标准治疗(SOC)激素疗法旨在调节雌激素及其受体(ERα和ERβ)的功能和表达水平。目前,芳香化酶抑制剂(AIs)、选择性雌激素受体调节剂(SERMs)和选择性雌激素受体降解剂(SERDs)被临床用于控制和治疗ER+ BC,其中芳香化酶抑制剂的抗芳香化酶活性可抑制雌激素的生物合成,而抗雌激素的SERMs和SERDs则可分别拮抗和降解ER。然而,SOC 激素疗法的使用因出现严重副作用和产生抗药性而受到严重阻碍。鉴于许多研究都报道了植物化合物和/或提取物的有益作用,以及它们针对ER+乳腺癌发生的多种途径,最近的研究集中于使用膳食化学预防剂来治疗乳腺癌。当这些植物成分和/或提取物与SOC疗法结合使用时,其中几种植物成分和/或提取物已显示出更好的疗效和/或协同作用。此外,尽管缺乏体内研究,但一般报告称植物产品的副作用低于 SOC 疗法,因此被认为是更安全的治疗选择。因此,本综述总结了过去五年中有关植物产品抗芳香化酶和抗雌激素活性的研究结果,以及它们与 SOC疗法结合的协同抗ER+ BC效果。
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引用次数: 0
Profile of key metabolites and identification of HMGCS1-DHEA pathway in porcine Sertoli cells treated by Vitamin C 用维生素 C 处理猪 Sertoli 细胞的关键代谢物概况和 HMGCS1-DHEA 通路的鉴定。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-10 DOI: 10.1016/j.jsbmb.2024.106580

Vitamin C (Ascorbic acid, AA), as vital micro-nutrient, plays an essential role for male animal reproduction. Previously, we showed that vitamin C reprogrammed the transcriptome and proteome to change phenotypes of porcine immature Sertoli cells (iSCs). Here, we used LC-MS-based non-targeted metabolomics to further investigate the metabolic effects of vitamin C on porcine iSCs. The results identified 43 significantly differential metabolites (DMs) (16 up and 27 down) as induced by vitamin C (L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) treatment of porcine iSCs, which were mainly enriched in steroid related and protein related metabolic pathways. ELISA (Enzyme-Linked ImmunoSorbent Assay) showed that significantly differential metabolites of Dehydroepiandrosterone (DHEA) (involved in steroid hormone biosynthesis) and Desmosterol (involved in steroid degradation) were significantly increased, which were partially consistent with metabolomic results. Further integrative analysis of metabolomics, transcriptomics and proteomics data identified the strong correlation between the key differential metabolite of Dehydroepiandrosterone and 6 differentially expressed genes (DEGs)/proteins (DEPs) (HMGCS1, P4HA1, STON2, LOXL2, EMILIN2 and CCN3). Further experiments validated that HMGCS1 could positively regulate Dehydroepiandrosterone level. These data indicate that vitamin C could modulate the metabolism profile, and HMGCS1-DHEA could be the pathway to mediate effects exerted by vitamin C on porcine iSCs.

维生素 C(抗坏血酸,AA)作为重要的微量营养素,对雄性动物的繁殖起着至关重要的作用。此前,我们曾发现维生素 C 可重构转录组和蛋白质组,从而改变猪未成熟 Sertoli 细胞(iSCs)的表型。在这里,我们使用基于 LC-MS 的非靶向代谢组学进一步研究了维生素 C 对猪 iSCs 的代谢影响。结果发现,维生素 C(L-抗坏血酸 2-磷酸倍半镁盐水合物,AA2P)处理猪 iSCs 可诱导 43 种明显不同的代谢物(16 种向上,27 种向下),这些代谢物主要富集在类固醇相关和蛋白质相关的代谢途径中。酶联免疫吸附试验(ELISA)显示,参与类固醇激素生物合成的脱氢表雄酮(DHEA)和参与类固醇降解的去甲斑蝥素(Desmosterol)的代谢物明显增加,这与代谢组学结果部分吻合。对代谢组学、转录组学和蛋白质组学数据的进一步综合分析发现,关键的差异代谢物脱氢表雄酮与 6 个差异表达基因(DEGs)/蛋白质(DEPs)(HMGCS1、P4HA1、STON2、LOXL2、EMILIN2 和 CCN3)之间存在很强的相关性。进一步的实验验证了 HMGCS1 能正向调节脱氢表雄酮的水平。这些数据表明,维生素 C 可调节新陈代谢,而 HMGCS1-DHEA 可能是维生素 C 对猪 iSCs 产生影响的途径。
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引用次数: 0
Seasonal changes in vitamin A metabolism-related factors in the oviduct of Chinese brown frog (Rana dybowskii) 中国褐蛙输卵管中维生素 A 代谢相关因子的季节性变化
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-09 DOI: 10.1016/j.jsbmb.2024.106583

The oviduct of the Chinese brown frog (Rana dybowskii) expands during pre-brumation rather than the breeding period, exhibiting a special physiological feature. Vitamin A is essential for the proper growth and development of many organisms, including the reproductive system such as ovary and oviduct. Vitamin A is metabolized into retinoic acid, which is crucial for oviduct formation. This study examined the relationship between oviducal expansion and vitamin A metabolism. We observed a significant increase in the weight and diameter of the oviduct in Rana dybowskii during pre-brumation. Vitamin A and its active metabolite, retinoic acid, notably increased during pre-brumation. The mRNA levels of retinol binding protein 4 (rbp4) and its receptor stra6 gene, involved in vitamin A transport, were elevated during pre-brumation compared to the breeding period. In the vitamin A metabolic pathway, the mRNA expression level of retinoic acid synthase aldh1a2 decreased significantly during pre-brumation, while the mRNA levels of retinoic acid α receptor (rarα) and the retinoic acid catabolic enzyme cyp26a1 increased significantly during pre-brumation, but not during the breeding period. Immunohistochemical results showed that Rbp4, Stra6, Aldh1a2, Rarα, and Cyp26a1 were expressed in ampulla region of the oviduct. Western blot results indicated that Aldh1a2 expression was lower, while Rbp4, Stra6, RARα, and Cyp26a1 were higher during pre-brumation compared to the breeding period. Transcriptome analyses further identified differential genes in the oviduct and found enrichment of differential genes in the vitamin A metabolism pathway, providing evidences for our study. These results suggest that the vitamin A metabolic pathway is more active during pre-brumation compared to the breeding period, and retinoic acid may regulate pre-brumation oviductal expansion through Rarα-mediated autocrine/paracrine modulation.

中国褐蛙(Rana dybowskii)的输卵管在发情前期而非繁殖期扩张,表现出一种特殊的生理特征。维生素 A 是许多生物(包括卵巢和输卵管等生殖系统)正常生长和发育所必需的物质。维生素 A 会代谢成视黄酸,而视黄酸对输卵管的形成至关重要。本研究探讨了输卵管扩张与维生素 A 代谢之间的关系。我们观察到雏鸟蜕皮前期输卵管的重量和直径明显增加。维生素 A 及其活性代谢物视黄酸在蜕皮前期明显增加。参与维生素A转运的视黄醇结合蛋白4(rbp4)及其受体stra6基因的mRNA水平在产卵前期比繁殖期升高。在维生素 A 代谢途径中,视黄酸合成酶 aldh1a2 的 mRNA 表达水平在蜕皮前期显著下降,而视黄酸 α 受体(larα)和视黄酸分解酶 cyp26a1 的 mRNA 水平在蜕皮前期显著上升,但在繁殖期则没有上升。免疫组化结果显示,Rbp4、Stra6、Aldh1a2、Rarα和Cyp26a1在输卵管安瓶区表达。Western 印迹结果表明,与繁殖期相比,Aldh1a2 的表达量在产卵前期较低,而 Rbp4、Stra6、RARα 和 Cyp26a1 的表达量较高。转录组分析进一步确定了输卵管中的差异基因,发现差异基因在维生素 A 代谢途径中富集,为我们的研究提供了证据。这些结果表明,与繁殖期相比,产卵前期维生素A代谢途径更为活跃,视黄酸可能通过Rarα介导的自分泌/旁分泌调节作用调控产卵前期的输卵管扩张。
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引用次数: 0
Effects of vitamin D supplementation on metabolic syndrome parameters in patients with obesity or diabetes in Brazil, Europe, and the United States: A systematic review and meta-analysis 维生素 D 补充剂对巴西、欧洲和美国肥胖症或糖尿病患者代谢综合征参数的影响:系统回顾和荟萃分析。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-09 DOI: 10.1016/j.jsbmb.2024.106582

Plasma 25-dihydroxyvitamin D levels appear reduced in patients with obesity or type 2 diabetes, as reported in several observational studies. However, the association between these reduced hormone levels and metabolic parameters is unclear. In any case, vitamin D supplementation in patients with Metabolic Syndrome is standard. Still, the impacts of this supplementation on conditions such as glycemia, blood pressure, and lipidemia are debatable. Based on this question, we carried out a systematic review and meta-analysis of randomized clinical trials in Brazil, Europe, and the United States that analyzed the effects of vitamin D supplementation on Metabolic Syndrome parameters in patients with obesity or type 2 diabetes. Our search yielded 519 articles and included 12 randomized controlled trials in the meta-analysis. Vitamin D supplementation had no effect on any of the outcomes analyzed (fasting blood glucose and insulinemia, glycated hemoglobin, HOMA index, systolic and diastolic blood pressure, weight, waist circumference, total cholesterol, LDL and HDL, and triglycerides). However, subgroup analyses indicated that using vitamin D up to 2000 IU daily reduced participants' fasting blood glucose and glycated hemoglobin. Furthermore, the intervention reduced diastolic blood pressure only in participants with vitamin D deficiency. At least two studies showed a high risk of bias using the Rob2 protocol. According to the GRADE protocol, the evidence quality varied from moderate to very low. These results indicate that vitamin D supplementation does not improve patients' metabolic parameters and that the association between plasma 25-dihydroxyvitamin D levels and Metabolic Syndrome may not be causal but caused by other confounding characteristics. However, in any case, the quality of evidence is still low, and more randomized clinical trials are essential to clarify these relationships.

据几项观察性研究报告,肥胖症或 2 型糖尿病患者的血浆 25-二羟维生素 D 水平似乎有所降低。然而,这些降低的激素水平与代谢参数之间的关系尚不清楚。无论如何,代谢综合征患者补充维生素 D 是标准做法。但是,这种补充对血糖、血压和血脂等情况的影响仍有争议。基于这一问题,我们对巴西、欧洲和美国的随机临床试验进行了系统回顾和荟萃分析,分析了补充维生素 D 对肥胖症或 2 型糖尿病患者代谢综合征参数的影响。我们共搜索到 519 篇文章,并在荟萃分析中纳入了 12 项随机对照试验。维生素 D 补充剂对任何分析结果(空腹血糖和胰岛素血症、糖化血红蛋白、HOMA 指数、收缩压和舒张压、体重、腰围、总胆固醇、低密度脂蛋白和高密度脂蛋白以及甘油三酯)均无影响。不过,亚组分析表明,每天服用多达 2000 IU 的维生素 D 可降低参与者的空腹血糖和糖化血红蛋白。此外,干预措施仅降低了维生素 D 缺乏症参与者的舒张压。根据 GRADE 协议,证据质量从中等到极低不等。这些结果表明,补充维生素 D 并不能改善患者的代谢参数,血浆 25-二羟维生素 D 水平与代谢综合征之间的关联可能不是因果关系,而是由其他混杂特征引起的。然而,无论如何,证据的质量仍然很低,更多的随机临床试验对于澄清这些关系至关重要。
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引用次数: 0
Ellagic acid mitigates heat-induced testicular detriment in a mouse model 鞣花酸可减轻小鼠模型中由热引起的睾丸损伤。
IF 2.7 2区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-08 DOI: 10.1016/j.jsbmb.2024.106576
Rahul Kumar , Vikash Kumar , Guruswami Gurusubramanian , Saurabh Singh Rathore , Vikas Kumar Roy

Heat stress has been shown to have a detrimental impact on testicular activity and spermatogenesis. Ellagic acid is a plant-derived organic compound that has a variety of biological functions. Thus, it is believed that ellagic acid may improve heat-stressed testicular dysfunction. There has been no research on the impact of ellagic acid on heat-stressed testicular dysfunction. The mice were divided into 4 groups. The first group was the normal control group (CN), and the second received heat stress (HS) by submerging the lower body for 15 min in a water bath with a thermostatically controlled temperature kept at 43°C (HS), and the third and fourth groups were subjected to heat-stress similar to group two and given two different dosages of ellagic acid (5 mg/kg (EH5) and 50 mg/kg (EH50) for 14 days. Ellagic acid at a dose of 50 mg/kg improved the level of circulating testosterone (increased 3βHSD) and decreases the oxidative stress. The testicular and epididymal architecture along with sperm parameters also showed improvement. Ellagic acid treatment significantly increases the germ cell proliferation (GCNA, BrdU staining) and Bcl2 expression and decreases active caspase 3 expression. Heat stress downregulated the expression of AR, ER-α and ER-β, and treatment with ellagic acid increased the expression of ER-α and ER-β markers in the 50 mg/kg treatment group. Thus, our finding suggests that ellagic acid ameliorates heat-induced testicular impairment through modulating testosterone synthesis, germ cell proliferation, and oxidative stress. These effects could be manifested by regulating androgen and estrogen receptors. However, the two doses showed differential effects of some parameters, which require further investigation.

研究表明,热应激会对睾丸活动和精子生成产生不利影响。鞣花酸是一种源自植物的有机化合物,具有多种生物功能。因此,人们认为鞣花酸可以改善热应激导致的睾丸功能障碍。目前还没有关于鞣花酸对热应激睾丸功能障碍影响的研究。小鼠被分为 4 组。第一组为正常对照组(CN),第二组接受热应激(HS),将下半身浸入恒温水浴中 15 分钟,温度保持在 43°C(HS),第三组和第四组接受与第二组类似的热应激,并给予两种不同剂量的鞣花酸(5 毫克/千克(EH5)和 50 毫克/千克(EH50),持续 14 天。剂量为 50 毫克/千克的鞣花酸提高了循环睾酮的水平(增加了 3βHSD),并降低了氧化应激。睾丸和附睾结构以及精子参数也有所改善。鞣花酸处理能明显增加生殖细胞的增殖(GCNA、BrdU 染色)和 Bcl2 的表达,降低活性 caspase 3 的表达。热应激下调了 AR、ER-α 和 ER-β 的表达,而鞣花酸处理可增加 50 毫克/公斤处理组中 ER-α 和 ER-β 标记的表达。因此,我们的研究结果表明,鞣花酸可通过调节睾酮合成、生殖细胞增殖和氧化应激来改善热引起的睾丸损伤。这些作用可能是通过调节雄激素和雌激素受体表现出来的。不过,两种剂量对某些参数的影响有所不同,需要进一步研究。
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引用次数: 0
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Journal of Steroid Biochemistry and Molecular Biology
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