Journal of Steroid Biochemistry and Molecular Biology最新文献_第10页

Gastric mucosal differentially expressed genes after bariatric surgery: Effects on sterol-related pathways 减肥手术后胃粘膜差异表达基因：对固醇相关途径的影响。

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-01 DOI: 10.1016/j.jsbmb.2025.106824

Maryam Mahjoubin-Tehran , Ali H. Eid , Tannaz Jamialahmadi , Saheem Ahmad , Safia Obaidur Rab , Prashant Kesharwani , Amirhossein Sahebkar

Obesity is currently recognized as a serious global health problem, which accounts for a considerable morbidity and mortality burden. Bariatric surgery is widely accepted as one of the most effective treatments for severe obesity. Roux-en-Y Gastric Bypass (RYGB) is a common type of bariatric surgery. Although the clinical impact of RYGB has been widely studied, the effects of this intervention at the molecular and genetic levels remain largely unknown. In this study, we aimed to identify differentially expressed genes in gastric mucosa after bariatric surgery vs. before in order to recognize genes and pathways influenced by surgery. Data of GSE76762 was downloaded from GEO (NCBI) database. Gene expression of after surgery samples were compared with before. Genes with a │Log fold change (LFC) │ > 1 and adjusted p-value < 0.05 were defined as differentially expressed genes. It was found that 11 genes were differentially upregulated and 6 genes were differentially downregulated after bariatric surgery. Protein-protein interactions assessed using STRNG online database was significant (p-value: 0.000202). SCD, INSIG1, CYP51A1, and LDLR have strong protein-protein interactions. Gene-gene interaction was investigated using GeneMANIA which showed the high co-expression score (97.78 %). GO and pathway enrichment analysis was investigated using EnrichR. Cholesterol Homeostasis, Sterol Homeostasis, and Cellular Response to Sterol are the best results of biological process. Metabolism of steroids, Steroid regulatory element binding proteins signaling, and Bile secretion are the best results of Reactome, WikiPathway, and KEGG, respectively. Importantly, associations of LDLR, KCNJ13, and PMP22 with Familial hypercholesterolemia, Hyperlipoproteinemia, Charcot-marie-tooth disease type 1 and 4, and Leber congenital amaurosis were discovered.

肥胖目前被认为是一个严重的全球健康问题，造成了相当大的发病率和死亡率负担。减肥手术被广泛认为是治疗严重肥胖最有效的方法之一。Roux-en-Y胃旁路手术（RYGB）是一种常见的减肥手术。尽管RYGB的临床影响已被广泛研究，但这种干预在分子和遗传水平上的影响在很大程度上仍然未知。在这项研究中，我们旨在鉴定减肥手术后与术前胃粘膜中差异表达的基因，以识别受手术影响的基因和途径。GSE76762的数据从GEO （NCBI）数据库下载。将术后标本的基因表达与术前进行比较。将│Log fold change （LFC）│> 1且调整后p值< 0.05的基因定义为差异表达基因。结果发现，减肥手术后11个基因差异上调，6个基因差异下调。使用string在线数据库评估的蛋白-蛋白相互作用具有显著性（p值：0.000202）。SCD、INSIG1、CYP51A1和LDLR具有很强的蛋白相互作用。采用GeneMANIA进行基因互作分析，共表达评分较高（97.78%）。利用enrichment分析氧化石墨烯和途径富集分析。胆固醇稳态、固醇稳态和细胞对固醇的反应是生物过程的最佳结果。类固醇代谢、类固醇调节元件结合蛋白信号传导和胆汁分泌分别是Reactome、WikiPathway和KEGG的最佳结果。重要的是，LDLR、KCNJ13和PMP22与家族性高胆固醇血症、高脂蛋白血症、1型和4型白斑病以及Leber先天性黑内障的相关性被发现。

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引用次数: 0

Phytosterols as modulators of gut-brain axis and neuroinflammation in Alzheimer’s disease: A novel therapeutic avenue in aging research 植物甾醇作为阿尔茨海默病肠脑轴和神经炎症的调节剂：衰老研究的新治疗途径

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-16 DOI: 10.1016/j.jsbmb.2025.106836

Nila Ganamurali , Varsha S B , Sarvesh Sabarathinam

Alzheimer’s disease (AD) is characterized by amyloid-β deposition and neuroinflammation. Emerging evidence implicates gut microbiota dysbiosis and gut–brain axis dysfunction in AD pathogenesis, while phytosterols—plant sterols similar to cholesterol—modulate microbiota composition, lipid metabolism, and inflammatory pathways. To review evidence of phytosterols as modulators of the gut–brain axis and neuroinflammation in AD, outlining mechanisms, therapeutic potential, and delivery approaches. A literature search of PubMed, Scopus, and Web of Science identified studies on phytosterols, gut microbiota modulation, neuroinflammation, and AD. Mechanistic data on sterol structure–activity relationships, microbiota-derived metabolites, and in vivo AD outcomes were extracted and synthesized. Phytosterols lower systemic cholesterol, cross the blood–brain barrier, and accumulate in neural tissue. They enrich short-chain fatty acid–producing gut microbes, suppress pathogens, and increase secondary bile acids that activate FXR and TGR5 signaling, attenuating neuroinflammation. Preclinical AD models show reduced amyloid-β, decreased microglial activation, and improved cognition. Nanoencapsulation and esterification strategies enhance CNS bioavailability. Phytosterols modulate cholesterol, gut microbiota, and neuroinflammatory pathways through FXR- and TGR5-mediated signaling. Advanced delivery systems and microbiome-informed dosing strategies may enhance their therapeutic precision and uptake. Future studies should focus on stratified human trials to validate efficacy and enable personalized interventions in Alzheimer’s disease.

阿尔茨海默病（AD）以淀粉样蛋白-β沉积和神经炎症为特征。新出现的证据表明，肠道菌群失调和肠-脑轴功能障碍在阿尔茨海默病的发病机制中，而植物甾醇-类似于胆固醇的植物甾醇-调节微生物群组成、脂质代谢和炎症途径。回顾植物甾醇作为AD患者肠-脑轴和神经炎症调节剂的证据，概述其机制、治疗潜力和给药途径。PubMed， Scopus和Web of Science的文献检索确定了植物甾醇，肠道微生物群调节，神经炎症和AD的研究。提取并合成了有关甾醇结构-活性关系、微生物衍生代谢物和体内AD结果的机制数据。植物甾醇降低全身胆固醇，穿过血脑屏障，并在神经组织中积累。它们丰富了产生短链脂肪酸的肠道微生物，抑制了病原体，增加了激活FXR和TGR5信号的次级胆汁酸，减轻了神经炎症。临床前AD模型显示淀粉样蛋白-β减少，小胶质细胞激活减少，认知能力改善。纳米胶囊化和酯化策略提高中枢神经系统的生物利用度。植物甾醇通过FXR-和tgr5介导的信号通路调节胆固醇、肠道菌群和神经炎症通路。先进的给药系统和微生物组信息的给药策略可以提高它们的治疗精度和摄取。未来的研究应侧重于分层人体试验，以验证阿尔茨海默病的疗效，并实现个性化干预。

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引用次数: 0

The role of cholesterol biosynthesis and metabolism causing medical complexity in patients with Smith-Lemli-Opitz Syndrome (SLOS) “胆固醇生物合成和代谢在史密斯-莱姆利-奥皮茨综合征（SLOS）患者中引起医疗复杂性的作用”。

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-01 DOI: 10.1016/j.jsbmb.2025.106822

Ellen Roy Elias

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic disorder associated with complex anatomic abnormalities, accompanied by medical, developmental and behavioral challenges. It was the first human disorder identified to be caused by an error in the complex cholesterol biosynthetic pathway, more than thirty years ago. This review will cover the clinical and developmental phenotype of patients with SLOS, and the understanding of how cholesterol deficiency, accumulation of the cholesterol precursors 7- and 8-dehydrocholesterol (7-DHC and 8-DHC), and the oxidation of these precursors into toxic oxysterols, are now known to cause this complex phenotype. There is a wide range of severity in patients with SLOS. The most severely affected babies may be miscarried or die in the newborn period due to lethal congenital anomalies. The most mildly impacted patients may show few anatomic abnormalities other than 2–3 toe syndactyly, but still display cognitive and behavioral challenges along the autism spectrum. The review will also cover the medical evaluation and interventions which are recommended in caring for patients with SLOS. There is no cure for this devastating disease, but certain interventions can lead to an improved quality of life, and stabilization of progressive problems for these complex patients.

Smith-Lemli-Opitz综合征（SLOS）是一种常染色体隐性遗传疾病，与复杂的解剖异常相关，伴有医学、发育和行为方面的挑战。这是30多年前发现的第一个由复杂的胆固醇生物合成途径中的错误引起的人类疾病。这篇综述将涵盖SLOS患者的临床和发育表型，并了解胆固醇缺乏、胆固醇前体7-和8-脱氢胆固醇（7- dhc和8-DHC）的积累以及这些前体氧化成有毒的氧甾醇是如何导致这种复杂表型的。sls患者的严重程度有很大的差别。受影响最严重的婴儿可能因致命的先天性异常而流产或在新生儿期死亡。最轻微的受影响的患者除了2-3个脚趾并指外，可能没有什么解剖异常，但仍然表现出自闭症谱系中的认知和行为挑战。审查还将包括在照顾慢活症患者时建议的医疗评价和干预措施。这种毁灭性的疾病无法治愈，但某些干预措施可以改善生活质量，并稳定这些复杂患者的进行性问题。

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引用次数: 0

An in-silico investigation of protein–ligand interactions involving dietary flavonoids targeting the nucleotide-binding domain 1 (NBD1) of multidrug resistance-associated protein 1 (MRP1) to overcome multidrug resistance in cancer 一项针对多药耐药相关蛋白1 （MRP1）核苷酸结合结构域1 （NBD1）的膳食黄酮类化合物的蛋白质-配体相互作用的计算机研究，以克服癌症的多药耐药

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-07 DOI: 10.1016/j.jsbmb.2025.106832

Khurshid Ahmad Padder

Multidrug resistance (MDR) continues to pose a tough challenge in the successful chemotherapeutic management of various malignancies. A key contributor to MDR is the multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding cassette (ABC) transporter family comprising 1531 amino acids. MRP1 actively extrudes a broad spectrum of chemotherapeutic agents from cancer cells, thereby reducing their intracellular accumulation and attenuating their cytotoxic effects. In this study, we performed molecular docking analyses to investigate the binding interactions between a series of naturally occurring dietary flavonoids and the Nucleotide Binding Domain 1 (NBD1) of MRP1, aiming to identify structural determinants that enhance ligand affinity and inform the selection of effective MDR modulators. All docking simulations were conducted using the Glide v5.7 software suite (Schrödinger LLC., Portland, USA) in extra precision mode (GlideXP). The 14 naturally occuring flavonoids assessed, rutin, taxifolin, myricetin, isorhamnetin, apigenin, eriodictyol, chrysin, daidzein and genistein exhibited variable binding affinities toward MRP1-NBD1, with several compounds forming key hydrogen bonds with active site amino acid residues. Notably, rutin demonstrated the highest binding affinity (docking score: –10.1958), forming highly stable hydrogen bonds with SER686 and SER689. Taxifolin and myricetin also showed favorable interactions, primarily involving SER686. These findings highlight the potential of specific dietary flavonoids to serve as functional inhibitors of MRP1-mediated drug efflux. Overall, the structural insights gained underscore the utility of flavonoid based scaffolds as promising candidates for overcoming MDR, thereby improving the therapeutic efficacy of anticancer agents.

多药耐药（MDR）继续对各种恶性肿瘤的成功化疗提出了严峻的挑战。多药耐药的一个关键因素是多药耐药相关蛋白1 (MRP1)，它是由1531个氨基酸组成的atp结合盒（ABC）转运蛋白家族的一员。MRP1积极地从癌细胞中挤出广谱的化疗药物，从而减少它们在细胞内的积累并减弱它们的细胞毒性作用。在这项研究中，我们进行了分子对接分析，研究了一系列天然存在的膳食黄酮类化合物与MRP1核苷酸结合域1 （NBD1）之间的结合相互作用，旨在确定增强配体亲和力的结构决定因素，并为选择有效的MDR调节剂提供信息。所有的对接模拟都是使用Glide v5.7软件套件（Schrödinger LLC., Portland， USA）在超精确模式（GlideXP）下进行的。被测的14种天然黄酮类化合物，芦丁、紫杉醇、杨梅素、异鼠李素、芹菜素、叶黄醇、菊花素、大豆苷元和染料木素与MRP1-NBD1的结合亲和力不同，其中一些化合物与活性位点氨基酸残基形成关键氢键。值得注意的是，芦丁具有最高的结合亲和力（对接分数：-10.1958），与SER686和SER689形成高度稳定的氢键。Taxifolin和杨梅素也表现出良好的相互作用，主要涉及SER686。这些发现强调了特定膳食类黄酮作为mrp1介导的药物外排的功能抑制剂的潜力。总的来说，这些结构上的见解强调了类黄酮支架作为克服耐多药的有希望的候选者的效用，从而提高了抗癌药物的治疗效果。

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引用次数: 0

Targeting 7-ketocholesterol-induced oxidative stress and inflammation: Guggulsterone as a novel vascular protectant 靶向7-酮胆固醇诱导的氧化应激和炎症：古古酮作为一种新的血管保护剂

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-08-25 DOI: 10.1016/j.jsbmb.2025.106846

Sarvesh Sabarathinam , Nila Ganamurali

7-Ketocholesterol (7-KC), a prominent oxysterol found in oxidized LDL, plays a central role in atherosclerosis through mechanisms involving oxidative stress, NF-κB activation, and mitochondrial dysfunction. Guggulsterone (GGS), a bioactive steroid from Commiphora mukul, exhibits antioxidant, anti-inflammatory, and FXR-antagonistic properties. This work highlights guggulsterone’s ability to counteract 7-KC-induced endothelial injury by inhibiting NF-κB translocation, reducing reactive oxygen species (ROS), and modulating apoptosis. These multimodal effects suggest guggulsterone as a promising natural agent for vascular protection. A systems-based pharmacological approach may further define its therapeutic utility in oxysterol-driven cardiovascular diseases.

7-酮胆固醇（7-KC）是在氧化LDL中发现的一种重要的氧甾醇，通过氧化应激、NF-κB激活和线粒体功能障碍等机制在动脉粥样硬化中起核心作用。Guggulsterone （GGS）是一种生物活性类固醇，具有抗氧化、抗炎和fxr拮抗剂的特性。这项工作强调了gugugulsterone通过抑制NF-κB易位、减少活性氧（ROS）和调节细胞凋亡来对抗7- kc诱导的内皮损伤的能力。这些多模态效应表明古固酮是一种很有前途的血管保护天然药物。基于系统的药理学方法可以进一步确定其在氧化甾醇驱动的心血管疾病中的治疗效用。

引用次数: 0

Sexual dimorphism and susceptibility to Alzheimer’s disease: Understanding genetic involvement and other risk factors 两性二态性与阿尔茨海默病的易感性：了解遗传参与和其他危险因素

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-08-13 DOI: 10.1016/j.jsbmb.2025.106843

Abayomi Oyeyemi Ajagbe , Abdulateef Ayoola Mobolaji , Oluwanisola Akanji Onigbinde , Tolulope Josiah Mosaku , Blessing Simon Oyeleye , Elizabeth Fisayo Ajenikoko-Ugbor , Al-Hassan Soliman Wadan , Abdulrahman Adesola Bello , Michael Kunle Ajenikoko , Ayodeji Zabdiel Abijo

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by persistent cognitive decli ne, tau-containing intracellular neurofibrillary tangles, and β-amyloid (Aβ)-containing extracellular plaques. Early symptoms include patchy memory loss and some behavioural abnormalities. There is a plethora of studies that have reported sexual dimorphism and a higher prevalence of Alzheimer's disease in women. However, the molecular mechanisms responsible for these differences remain an enigma. The increasing aging population, as well as the decline in estrogen levels, have been attributed to increased risk in the development of AD in women. Hormone replacement therapy (HRT) has been proposed as an approach for tackling the increased AD susceptibility in women; increased AD vulnerability in men is also linked to testosterone levels. In addition to the hormonal influence as one of the causative factors for increased risk of AD, there is the involvement of genetic factors, with APOE ε4 gene documented as a risk gene leading to tau pathological changes in the brain of female AD patients. Here, we aim to systematically examine literature on the factors and molecular mechanisms responsible for sexual dimorphism in increased vulnerability and pathological features of AD, with the hope that it may provide information on the diagnosis and therapeutic interventions in AD.

阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是持续的认知能力下降，含有tau的细胞内神经原纤维缠结和含有β-淀粉样蛋白（a β）的细胞外斑块。早期症状包括局部记忆丧失和一些行为异常。有大量的研究报告了两性异形和阿尔茨海默病在女性中的较高患病率。然而，造成这些差异的分子机制仍然是一个谜。人口老龄化的加剧，以及雌激素水平的下降，都被认为是女性患AD风险增加的原因。激素替代疗法（HRT）已被提出作为解决女性阿尔茨海默病易感性增加的方法；男性阿尔茨海默病的易感性增加也与睾丸激素水平有关。除了激素影响是AD风险增加的原因之一外，遗传因素也参与其中，APOE ε4基因是导致女性AD患者大脑tau病变的危险基因。在这里，我们的目的是系统地检查有关AD易感性增加和病理特征中两性二态性的因素和分子机制的文献，希望它可以为AD的诊断和治疗干预提供信息。

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引用次数: 0

Polycystic ovary syndrome: The role of granulosa cell proliferation and apoptosis in disease development 多囊卵巢综合征：颗粒细胞增殖和凋亡在疾病发展中的作用

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-26 DOI: 10.1016/j.jsbmb.2025.106838

Yao Yi , Yu Zhong , Rui-Ning Liang , Cheng-Yi Liu , Yi-Feng Zhang , Yi-Xuan Zhang

Polycystic ovary syndrome (PCOS) is the most prevalent ovarian endocrine disorder in infertile women and significantly impacts their health. Granulosa cell (GC) is the largest functional cell type in follicular development and plays a crucial role in follicle growth, differentiation, and maturation. Studies have shown that women with PCOS experience abnormal GC proliferation and apoptosis, which contribute to symptoms such as inflammation, irregular estrous cycles, hormonal imbalances, and follicular development arrest. These findings suggest that altered GC quantity is a key factor in the pathogenesis and progression of PCOS. Nevertheless, substantial inconsistencies exist in studies regarding GC number changes in PCOS follicles. To explore the underlying causes, we reviewed recent literature on GC proliferation and apoptosis in PCOS over the past years. This review identifies several potential causes contributing to these discrepancies, including overlooked follicular-phase-dependent effects on GC quantity, variations in GC sources (PCOS vs. non-PCOS, human vs. animal models, and human immortalized granulosa cells), and the lack of animal model validation, inadequate detection of relevant indicators, and unclear identification of vital influential factors. To address these issues, we propose several potential solutions to provide valuable insights into elucidating the roles of GC proliferation and apoptosis, their regulatory mechanisms, and potential therapeutic strategies in PCOS.

多囊卵巢综合征（PCOS）是不孕妇女中最常见的卵巢内分泌疾病，严重影响其健康。颗粒细胞（Granulosa cell， GC）是卵泡发育中最大的功能细胞类型，在卵泡生长、分化和成熟过程中起着至关重要的作用。研究表明，多囊卵巢综合征的女性会经历异常的GC增殖和凋亡，从而导致炎症、月经周期不规则、激素失衡和卵泡发育停滞等症状。这些结果提示GC量的改变是PCOS发病和发展的关键因素。然而，关于PCOS卵泡中GC数变化的研究存在很大的不一致性。为了探讨其潜在的原因，我们回顾了近年来关于PCOS中GC增殖和凋亡的最新文献。本综述确定了导致这些差异的几个潜在原因，包括忽略了卵泡期对GC量的依赖作用，GC来源的变化（PCOS与非PCOS，人类与动物模型，人类永生化颗粒细胞），缺乏动物模型验证，相关指标检测不足，以及对重要影响因素的不明确识别。为了解决这些问题，我们提出了几种可能的解决方案，为阐明GC增殖和凋亡的作用、它们的调节机制和PCOS的潜在治疗策略提供有价值的见解。

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引用次数: 0

Identification of cholesterol homeostasis related genes and potential pathogenesis mechanisms in ulcerative colitis 溃疡性结肠炎胆固醇稳态相关基因的鉴定及其潜在的发病机制

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-09 DOI: 10.1016/j.jsbmb.2025.106833

Jie Wan , Yuchao Zhang , Ning Ge , Hongya Guan , Jia Liu

Background and aims

Cholesterol metabolism (CM) plays essential roles in human disease. Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with significant morbidity and healthcare burden. However, the role of CM in UC remains unclear.

Methods

Gene expression data of UC patients and control samples were retrieved and merged from GSE75214, GSE92415, GSE16879, and GSE48958. Differential analysis was performed for the identification of cholesterol homeostasis-related differentially expressed genes (DEGs), followed by machine learning for cholesterol homeostasis-related hub DEGs. Five cholesterol homeostasis related genes were identified. We further assessed the related pathways of 5 hub genes.

Results

Five overlapped cholesterol homeostasis related genes were identified by DEGs analysis. LIPC, LIPG, CETP, ABCB11, and APOH were identified as hub genes.

Conclusions

The current study identified 5 cholesterol homeostasis related genes, LIPC, LIPG, CETP, ABCB11, and APOH, that might play key roles in the development of UC. These findings offer new insights for further exploring UC and its underlying mechanisms.

背景与目的胆固醇代谢（CM）在人类疾病中起着重要作用。溃疡性结肠炎（UC）是一种慢性炎症性肠病，具有显著的发病率和医疗负担。然而，CM在UC中的作用仍不清楚。方法检索UC患者和对照样本GSE75214、GSE92415、GSE16879和GSE48958基因表达数据并进行合并。对胆固醇稳态相关的差异表达基因（DEGs）进行差异分析，然后对胆固醇稳态相关的中心DEGs进行机器学习。鉴定出5个胆固醇稳态相关基因。我们进一步评估了5个枢纽基因的相关通路。结果通过DEGs分析鉴定出5个重叠的胆固醇稳态相关基因。中心基因为LIPC、LIPG、CETP、ABCB11和APOH。结论本研究发现5个胆固醇稳态相关基因LIPC、LIPG、CETP、ABCB11和APOH可能在UC的发生发展中起关键作用。这些发现为进一步探索UC及其潜在机制提供了新的见解。

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引用次数: 0

Obituary Étienne-Émile Baulieu (1927–2025) 讣告：Etienne - Emile Baulieu（1927-2025）。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-16 DOI: 10.1016/j.jsbmb.2025.106834

Jerzy Adamski

引用次数: 0

Very high-dose vitamin D₃ supplementation reduces the expression of genes and proteins engaged in β-oxidation in healthy pigs 非常高剂量的维生素D₃可以减少健康猪体内参与β-氧化的基因和蛋白质的表达

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2025-11-01 Epub Date: 2025-07-16 DOI: 10.1016/j.jsbmb.2025.106835

Anna Steg , Grzegorz Smołucha , Małgorzata Świątkiewicz , Maria Oczkowicz

Vitamin D plays a multifaceted role in the body, influencing a wide range of physiological processes. While its benefits in deficiency states are well recognized, the effects of high-dose vitamin D₃ supplementation in vitamin D-sufficient individuals remain poorly understood. In this study, we applied an integrative transcriptomic and proteomic approach to assess the dose-dependent effects of long-term dietary vitamin D₃ supplementation (5000 and 10,000 IU/kg feed) in healthy pigs. Despite the absence of phenotypic alterations in fattening characteristics, we observed significant molecular changes in liver tissue, particularly in pathways related to fatty acid β-oxidation, amino acid catabolism, and oxidative stress response. High-dose vitamin D₃ supplementation led to consistent downregulation of key genes and proteins involved in mitochondrial and peroxisomal β-oxidation, including ACSL5, ACADVL, HADHA, ACAA1 (gene expression), and ACADM, ECHDC1, and ECHDC2 (protein level). These findings suggest a reduced hepatic capacity for activating and degrading long-, very long-, and medium-chain fatty acids, potentially resulting in the accumulation of lipid intermediates and a shift toward alternative metabolic pathways. Our findings indicate that very high-dose vitamin D₃ supplementation in non-deficient states may lead to adverse metabolic shifts in the liver, including lipid accumulation and compromised energy metabolism. These effects appear to be dose-dependent, and while they may not manifest phenotypically in short-lived species, they offer important insights into non-classical toxicological effects of high-dose vitamin D₃ supplementation. Importantly, this study highlights the context-dependent nature of vitamin D’s effects and provides a new direction for research focused on its metabolic roles beyond classical pathways.

维生素D在人体中起着多方面的作用，影响着广泛的生理过程。虽然它对缺乏维生素D的人的好处已经得到了充分的认识，但对维生素D充足的人补充高剂量维生素D₃的影响仍然知之甚少。在这项研究中，我们应用了综合转录组学和蛋白质组学方法来评估健康猪的长期膳食维生素D₃补充（5000和10000 IU/kg饲料）的剂量依赖效应。尽管增肥特征没有表型改变，但我们观察到肝组织中显著的分子变化，特别是在脂肪酸β氧化、氨基酸分解代谢和氧化应激反应相关的途径中。高剂量补充维生素D₃导致参与线粒体和过氧化物酶体β-氧化的关键基因和蛋白质的持续下调，包括ACSL5、ACADVL、HADHA、ACAA1（基因表达）和ACADM、ECHDC1、ECHDC2（蛋白质水平）。这些发现表明，肝脏激活和降解长链、超长链和中链脂肪酸的能力降低，可能导致脂质中间体的积累，并向替代代谢途径转变。我们的研究结果表明，在非缺乏状态下，非常高剂量的维生素D₃补充可能会导致肝脏的不良代谢变化，包括脂质积累和能量代谢受损。这些影响似乎是剂量依赖的，虽然它们可能不会在短命物种中表现出表型，但它们为高剂量维生素D₃补充剂的非经典毒理学效应提供了重要的见解。重要的是，这项研究强调了维生素D作用的环境依赖性，并为关注其在经典途径之外的代谢作用的研究提供了一个新的方向。

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引用次数: 0