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Integration of inter-simple sequence repeats with machine learning approach for diversity analysis and authentication of Iranian cotton cultivars 基于简单重复序列的伊朗棉品种多样性分析与鉴定
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102435
Rasmieh Hamid , Zahra Ghorbanzadeh , Bahman Panahi
Cotton (Gossypium hirsutum L.) has experienced extensive breeding in recent decades, leading to a narrowed genetic base that presents challenges for accurate germplasm differentiation and cultivar authentication. This study primarily addresses the lack of reliable, scalable, and interpretable tools for distinguishing closely related Iranian cotton cultivars. To overcome this limitation, the research integrates inter-simple sequence repeat (ISSR) markers with machine learning (ML) algorithms to evaluate genetic diversity and establish diagnostic criteria for cultivar identification. Eighteen commercial cultivars were genotyped using 14 ISSR primers and binary scored data (presence/absence of bands) were used to calculate genetic diversity parameters, including the observed number of alleles (Na), effective number of alleles (Ne), Shannon's information index (I), and expected heterozygosity (He) were calculated. Primers 13, 10, and 26 were identified as the most informative loci, yielding the highest values across diversity parameters. Unweighted Pair Group Method with Arithmetic Mean (UPGMA) clustering and principal coordinates analysis (PCoA) revealed five cultivar groups, with several accessions (e.g., Jahesh, Fakhr, Sahel) showing marked genetic distinctiveness. To enhance cultivar authentication, ISSR data were analyzed using ML classifiers. A decision tree model generated transparent band-based rules, while Random Forest feature selection highlighted key diagnostic loci (Primer24_525, Primer2_766). The combined framework achieved high classification accuracy and reproducibility, enabling reliable discrimination among closely related cultivars. These findings demonstrate the novelty and practical utility of integrating multilocus ISSR markers with ML for cultivar authentication, seed certification, and genetic resource management, while also highlighting previously underexplored genetic diversity that can inform cotton breeding programs in Iran.
近几十年来,棉花(Gossypium hirsutum L.)经历了广泛的育种,导致遗传基础缩小,这给准确的种质分化和品种鉴定带来了挑战。本研究主要解决缺乏可靠、可扩展和可解释的工具来区分密切相关的伊朗棉花品种。为了克服这一限制,本研究将ISSR标记与机器学习算法相结合,以评估遗传多样性并建立品种鉴定的诊断标准。利用14条ISSR引物对18个商品品种进行基因分型,利用二元评分数据(条带存在/缺失)计算遗传多样性参数,包括观察等位基因数(Na)、有效等位基因数(Ne)、香农信息指数(I)和期望杂合度(He)。引物13、10和26被确定为信息量最大的位点,在多样性参数中产生最高的值。利用UPGMA聚类和主坐标分析(PCoA)的非加权对类群分析发现了5个品种类群,其中Jahesh、Fakhr、Sahel等品种表现出显著的遗传差异。为了加强品种鉴定,利用ML分类器对ISSR数据进行分析。决策树模型生成透明的基于频带的规则,而随机森林特征选择突出了关键诊断位点(Primer24_525, Primer2_766)。该组合框架具有较高的分类精度和可重复性,能够对近缘品种进行可靠的鉴别。这些发现证明了将多位点ISSR标记与ML结合用于品种鉴定、种子认证和遗传资源管理的新颖性和实用性,同时也强调了以前未被充分开发的遗传多样性,可以为伊朗的棉花育种计划提供信息。
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引用次数: 0
Study on the processing transformation law of CATR and ATR in Xanthii Fructus and the metabolomics mechanism of their transformation products in LO2 cells 苍耳子中CATR和ATR加工转化规律及其转化产物在LO2细胞中的代谢组学机制研究
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102436
Lingling Wang , Huihao Ao , Cheng Huang , Deling Wu , Yan Hong , Yanquan Han

Background

The thermal processing of Xanthii Fructus is known to attenuate its hepatotoxicity. Carboxyatractyloside (CATR) and atractyloside (ATR), the primary toxic constituents, exhibit differential toxicity, with CATR being more potent. While the conversion of CATR to the less toxic ATR during processing is believed to underlie this toxicity reduction, the precise conversion dynamics and associated molecular mechanisms remain to be fully elucidated.

Purpose

This study aimed to elucidate the mechanisms responsible for the reduced hepatotoxicity of Xanthii Fructus following sand-frying. We employed an integrated approach combining ultra-high-performance liquid chromatography (UHPLC), metabolomics, and network pharmacology to investigate the differences in chemical composition and toxicological pathways between the crude and processed herb.

Methods

The UHPLC method was used to establish fingerprint of Xanthii Fructus from different origins before and after processing, and the contents of CATR and ATR were determined. The thermal conversion and comparative toxicity of these compounds were subsequently evaluated. Cellular metabolomics was performed to identify differential metabolites and perturbed pathways, while network pharmacology and molecular docking were used to predict and validate primary protein targets and their binding affinities.

Results

The attenuated hepatotoxicity was primarily attributed to the thermal conversion of CATR to ATR. Metabolomic analysis revealed that CATR significantly impacted alanine, aspartate, and glutamate metabolism and the TCA cycle, whereas ATR predominantly affected pyrimidine, arginine, and proline metabolism. Glutathione metabolism was a common pathway for both. Molecular docking simulations showed that CATR exhibited a stronger binding affinity than ATR towards key protein targets (DSS, DESG2, and ENTPD1), which is consistent with its greater toxicity.
研究背景苍耳子经热处理可减轻其肝毒性。主要毒性成分为羧基白术苷(CATR)和白术苷(ATR),两者毒性差异较大,其中CATR毒性更强。虽然在加工过程中将CATR转化为毒性较低的ATR被认为是这种毒性降低的基础,但精确的转化动力学和相关的分子机制仍有待充分阐明。目的探讨苍耳子煎炸后降低肝毒性的作用机制。采用超高效液相色谱(UHPLC)、代谢组学和网络药理学相结合的综合方法,研究了生药材和加工药材的化学成分和毒理学途径的差异。方法采用高效液相色谱法建立不同产地苍耳子炮制前后的指纹图谱,并测定其CATR和ATR的含量。随后对这些化合物的热转化和相对毒性进行了评价。细胞代谢组学用于鉴定差异代谢物和扰动通路,网络药理学和分子对接用于预测和验证主要蛋白靶点及其结合亲和力。结果肝毒性的减弱主要是由于CATR向ATR的热转化所致。代谢组学分析显示,CATR显著影响丙氨酸、天冬氨酸和谷氨酸的代谢和TCA循环,而ATR主要影响嘧啶、精氨酸和脯氨酸的代谢。谷胱甘肽代谢是两者的共同途径。分子对接模拟结果显示,与ATR相比,CATR对关键蛋白靶点(DSS、DESG2和ENTPD1)具有更强的结合亲和力,这与其更大的毒性是一致的。
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引用次数: 0
Hibiscus sabdariffa calyx aqueous extract mitigates alcohol withdrawal-induced anxiety and oxidative stress in mice 芙蓉花萼水提物减轻小鼠酒精戒断诱导的焦虑和氧化应激
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102423
Nadège Emégam Kouémou , Louis Aimé Sepi , Mireille Sylviane Nguepi Dongmo , Ndzweng Linda Tamanji , Franklin Savo Mbeboh , Stephanie Jacqueline Kameni Ndjapdounke , Paul Aimé Noubissi , Bernard Tiencheu , Elisabeth Ngo Bum

Background

Alcohol withdrawal syndrome (AWS) happens following a sudden interruption of chronic alcohol intake. AWS is a severe condition, often leading to anxiety and seizures. Current treatments against AWS do not target all the features of the disease. This study aimed to evaluate Hibiscus sabdariffa aqueous extract on AWS in mice.

Methods

Thirty-five male mice were grouped into seven sets of 5 animals. Each set (except the sham control) received alcohol (5 %) as drinking water and, in addition, alcohol at increasing concentrations (5 %–35 %, 0.4 g/kg to 2.8 g/kg) once every 24 h for 28 days. After alcohol weaning on day 29, anxiety was evaluated (days 29–31). Following behavioural recording, animals were euthanised. Brain and liver homogenates were used for biochemical evaluation of oxidative stress parameters. Alanine aminotransferase and Aspartate aminotransferase were assessed in the serum.

Results

Alcohol withdrawal led to a significant (P < 0.001) decrease in open arm activities in the elevated plus maze. Hibiscus sabdariffa administration reversed the ethanol effect and increased open arms stay and exploration. Hibiscus sabdariffa also significantly (P < 0.05) increased center exploration of the open field, which was reduced by alcohol withdrawal. A treatment with Hibiscus sabdariffa significantly (P < 0.01) reduced the increase of brain and liver oxidation induced by alcohol withdrawal. Serum Alanine aminotransferase level was also significantly (P < 0.001) decreased by Hibiscus sabdariffa extract.

Conclusion

This study's results justify the traditional utilisation of the drinks prepared from Hibiscus sabdariffa cayxes in treating patients suffering from AWS.
背景:酒精戒断综合征(AWS)发生在慢性酒精摄入突然中断后。AWS是一种严重的疾病,通常会导致焦虑和癫痫发作。目前针对AWS的治疗方法并没有针对该疾病的所有特征。本研究旨在评价芙蓉水提物对小鼠AWS的影响。方法35只雄性小鼠分为7组,每组5只。每组(假对照组除外)均以酒精(5 %)作为饮用水,此外,每24 h增加一次浓度的酒精(5 % -35 %,0.4 g/kg至2.8 g/kg),持续28天。第29天戒酒后,评估焦虑(第29 - 31天)。在行为记录之后,对动物实施安乐死。用脑和肝脏匀浆进行氧化应激参数的生化评价。测定血清丙氨酸转氨酶和天冬氨酸转氨酶。结果酒精戒断导致高架+迷宫中张开臂活动显著降低(P <; 0.001)。芙蓉提取物逆转了乙醇效应,增加了张开的手臂停留和探索。芙蓉也显著(P <; 0.05)增加了裸地的中心探索,酒精戒断降低了中心探索。木槿提取物显著(P <; 0.01)降低了酒精戒断引起的脑和肝脏氧化的增加。木槿提取物也显著降低了血清丙氨酸转氨酶水平(P <; 0.001)。结论本研究的结果证明了传统的利用芙蓉饮料治疗AWS患者是合理的。
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引用次数: 0
Investigating the inflammatory response to exposure of ultrafine TiO2 particulate matter to HUVECs 研究超细TiO2颗粒物质暴露于HUVECs的炎症反应
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102426
Laura A.E. Brunmaier, Travis W. Walker
Epidemiological studies have indicated that strong causal evidence exists to link the inhalation of particulate matter to the exacerbation of pathology in the cardiovascular system, ranging from myocardial infarction and atherosclerosis to direct cytotoxicity and inflammation. Ultrafine particles are ubiquitous in ambient air, in industrial sites, and in air pollution. When particles are inhaled, deposition can occur in the lungs, and the mechanisms of pathology have been well-studied. However, ultrafine particulate matter can translocate from the lungs into the bloodstream to circulate throughout the body (Choi et al. 2010).Contradictory evidence exists of inflammation and cytotoxicity that is caused from nanoparticle exposure to the endothelium.
When endothelial cells (ECs) are adversely stimulated, they have been shown to secrete cytokines that mediate an inflammatory response. Currently, studies that quantitatively evaluated the secretion of pro-inflammatory cytokines from ECs upon nanoparticle exposure are not accounting for the aggregation that can occur between particles over time and, therefore, are likely exposing cells to a wider range of aggregated sizes. This study evaluates the inflammatory response from ECs after particle exposure, with acute attention devoted to controlling particle aggregation. Specifically, we introduce a protocol that exposes ECs to the particles in a transwell system, where we take advantage of the effects of gravitational settling to expose the ECs only to the smallest fraction of the particles that are in suspension. After 72 h in the transwell assay, we found that the inflammatory response between varying concentrations of particles mirrored the inflammatory response of the positive control of lipopolysaccharide (LPS). These results indicate that the inflammatory response may have a stronger relationship to the particle size than to the concentration of the particles in mass per volume.
流行病学研究表明,有强有力的因果证据表明,颗粒物质的吸入与心血管系统的病理恶化有关,从心肌梗死和动脉粥样硬化到直接的细胞毒性和炎症。超细颗粒在环境空气、工业场所和空气污染中无处不在。当颗粒被吸入,沉积可发生在肺部,病理机制已被充分研究。然而,超细颗粒物可以从肺部转移到血液中,在全身循环(Choi et al. 2010)。存在相互矛盾的证据表明,炎症和细胞毒性是由纳米颗粒暴露于内皮细胞引起的。当内皮细胞(ECs)受到不良刺激时,它们已被证明会分泌介导炎症反应的细胞因子。目前,定量评估纳米颗粒暴露后内皮细胞促炎细胞因子分泌的研究并没有考虑颗粒之间随着时间的推移可能发生的聚集,因此,可能会使细胞暴露于更大范围的聚集大小。本研究评估颗粒暴露后ECs的炎症反应,重点关注控制颗粒聚集。具体来说,我们引入了一种将ec暴露于transwell系统中的粒子的协议,在该协议中,我们利用重力沉降的影响,使ec仅暴露于悬浮粒子的最小部分。在transwell实验72小时后,我们发现不同浓度颗粒之间的炎症反应反映了脂多糖(LPS)阳性对照的炎症反应。这些结果表明,炎症反应可能与颗粒大小的关系比与每体积颗粒的质量浓度的关系更强。
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引用次数: 0
Nanochelate-based BCc1 delivery and its impact on key regulatory pathways in BALB/c breast cancer: An analysis of Beclin-1, ATG-4B, ATG-7, and mTOR expression 基于纳米螯合剂的BCc1传递及其对BALB/c乳腺癌关键调控途径的影响:Beclin-1、ATG-4B、ATG-7和mTOR表达的分析
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102418
Fereshteh Moheb Afzali , Masoumeh Heshmati , Ali Salimi , Somayeh Kalanaky , Saideh Fakharzadeh , Maryam Hafizi , Mohammad Esmail Akbari , Mohammad Hassan Nazaran , Mehrdad Hashemi

Background

Breast cancer (BC) ranks as the most prevalent cancer type among women globally. Nanoparticle technology, a promising approach, plays a crucial role in effective cancer diagnosis and treatment. In this context, researchers investigated the efficacy of BCc1 nanomedicine, which utilizes nanochelating technology and possesses anti-neoplastic properties, in mice with breast tumors. Notably, this study represents the first global exploration of BCc1 nanomedicine's potential to induce autophagy, a process mediated by autophagy-related genes (Beclin-1, ATG-4B, ATG-7, and mTOR), while evaluating tumor cell death.

Methods

In this study, female BALB/c mice bearing 4T1 mammary tumors received daily treatments with BCc1 nanomedicine for 24 consecutive days via two administration routes: intraperitoneal (i.p.) injection and oral administration by gavage. The research investigated the impact of BCc1 nanomedicine on autophagy induction. Importantly, BCc1 nanomedicine played a role in mitigating tumor cell death severity by activating essential genes. Real-time PCR facilitated detailed gene expression analysis during the 24-day treatment period.

Results

Cyclophosphamide and BCc1 nanomedicine exhibited distinct regulatory effects on autophagy-associated genes. Beclin-1 expression was significantly upregulated in both cyclophosphamide-treated and BCc1-administered groups compared to controls. In BCc1-treated mice, ATG-4B and ATG-7—genes essential for autophagosome formation and maturation—were markedly downregulated across all dosing regimens. Concurrently, BCc1 induced a significant reduction in mTOR expression, consistent with the removal of a major inhibitory checkpoint in autophagy initiation. Taken together, these findings suggest that BCc1 exerts a stage-specific influence on autophagy, potentially enhancing its initiation phase while attenuating subsequent maturation steps.

Conclusion

In summary, BCc1 nanomedicine demonstrates therapeutic potential in BC, in part through the modulation of autophagy pathways. The observed gene expression profile—characterized by mTOR suppression and Beclin-1 upregulation alongside reduced ATG-4B and ATG-7 expression—indicates a selective enhancement of autophagy initiation, coupled with alterations in autophagosome maturation. This nuanced modulation of autophagy may contribute to BCc1's anti-tumor activity and warrants further investigation into its stage-specific mechanistic effects in cancer therapy.
乳腺癌(BC)是全球女性中最常见的癌症类型。纳米粒子技术是一种很有前途的方法,在有效的癌症诊断和治疗中起着至关重要的作用。在此背景下,研究人员研究了BCc1纳米药物对乳腺肿瘤小鼠的疗效。BCc1纳米药物利用纳米螯合技术,具有抗肿瘤特性。值得注意的是,这项研究首次在全球范围内探索了BCc1纳米药物诱导自噬的潜力,这是一个由自噬相关基因(Beclin-1、ATG-4B、ATG-7和mTOR)介导的过程,同时评估了肿瘤细胞的死亡。方法采用BCc1纳米药物腹腔注射和灌胃给药两种给药途径,连续给药24 d。研究BCc1纳米药物对细胞自噬诱导的影响。重要的是,BCc1纳米药物通过激活必需基因来减轻肿瘤细胞死亡的严重程度。实时荧光定量PCR有助于在24天的治疗期间详细分析基因表达。结果环磷酰胺和BCc1纳米药物对细胞自噬相关基因有明显的调控作用。与对照组相比,环磷酰胺处理组和bcc1给药组Beclin-1的表达均显著上调。在bcc1处理的小鼠中,ATG-4B和atg -7基因对自噬体的形成和成熟至关重要,在所有给药方案中都明显下调。同时,BCc1诱导mTOR表达显著降低,这与自噬启动过程中主要抑制检查点的去除一致。综上所述,这些发现表明BCc1对自噬具有阶段特异性影响,可能会增强其起始阶段,同时减弱随后的成熟步骤。综上所述,BCc1纳米药物在BC中显示出治疗潜力,部分是通过调节自噬途径实现的。观察到的基因表达谱-以mTOR抑制和Beclin-1上调以及ATG-4B和ATG-7表达降低为特征-表明自噬起始选择性增强,以及自噬体成熟的改变。这种细微的自噬调节可能有助于BCc1的抗肿瘤活性,值得进一步研究其在癌症治疗中的阶段性机制作用。
{"title":"Nanochelate-based BCc1 delivery and its impact on key regulatory pathways in BALB/c breast cancer: An analysis of Beclin-1, ATG-4B, ATG-7, and mTOR expression","authors":"Fereshteh Moheb Afzali ,&nbsp;Masoumeh Heshmati ,&nbsp;Ali Salimi ,&nbsp;Somayeh Kalanaky ,&nbsp;Saideh Fakharzadeh ,&nbsp;Maryam Hafizi ,&nbsp;Mohammad Esmail Akbari ,&nbsp;Mohammad Hassan Nazaran ,&nbsp;Mehrdad Hashemi","doi":"10.1016/j.bbrep.2025.102418","DOIUrl":"10.1016/j.bbrep.2025.102418","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) ranks as the most prevalent cancer type among women globally. Nanoparticle technology, a promising approach, plays a crucial role in effective cancer diagnosis and treatment. In this context, researchers investigated the efficacy of BCc1 nanomedicine, which utilizes nanochelating technology and possesses anti-neoplastic properties, in mice with breast tumors. Notably, this study represents the first global exploration of BCc1 nanomedicine's potential to induce autophagy, a process mediated by autophagy-related genes (<em>Beclin-1</em>, <em>ATG-4B</em>, <em>ATG-7</em>, and <em>mTOR</em>), while evaluating tumor cell death.</div></div><div><h3>Methods</h3><div>In this study, female BALB/c mice bearing 4T1 mammary tumors received daily treatments with BCc1 nanomedicine for 24 consecutive days via two administration routes: intraperitoneal (i.p.) injection and oral administration by gavage. The research investigated the impact of BCc1 nanomedicine on autophagy induction. Importantly, BCc1 nanomedicine played a role in mitigating tumor cell death severity by activating essential genes. Real-time PCR facilitated detailed gene expression analysis during the 24-day treatment period.</div></div><div><h3>Results</h3><div>Cyclophosphamide and BCc1 nanomedicine exhibited distinct regulatory effects on autophagy-associated genes. <em>Beclin-1</em> expression was significantly upregulated in both cyclophosphamide-treated and BCc1-administered groups compared to controls. In BCc1-treated mice, <em>ATG-4B</em> and <em>ATG-7</em>—genes essential for autophagosome formation and maturation—were markedly downregulated across all dosing regimens. Concurrently, BCc1 induced a significant reduction in <em>mTOR</em> expression, consistent with the removal of a major inhibitory checkpoint in autophagy initiation. Taken together, these findings suggest that BCc1 exerts a stage-specific influence on autophagy, potentially enhancing its initiation phase while attenuating subsequent maturation steps.</div></div><div><h3>Conclusion</h3><div>In summary, BCc1 nanomedicine demonstrates therapeutic potential in BC, in part through the modulation of autophagy pathways. The observed gene expression profile—characterized by <em>mTOR</em> suppression and <em>Beclin-1</em> upregulation alongside reduced <em>ATG-4B</em> and <em>ATG-7</em> expression—indicates a selective enhancement of autophagy initiation, coupled with alterations in autophagosome maturation. This nuanced modulation of autophagy may contribute to BCc1's anti-tumor activity and warrants further investigation into its stage-specific mechanistic effects in cancer therapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102418"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mammalian fatty acid synthase and O-GlcNAc transferase preferentially interact via their respective N-terminal regions 哺乳动物脂肪酸合成酶和O-GlcNAc转移酶通过各自的n端区域优先相互作用
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102427
Dimitri Vanauberg, Céline Schulz, Guillaume Brysbaert, Nessim Raouraoua, Peggy Mistarz-Gruau, Marc F. Lensink, Anne-Sophie Vercoutter-Edouart, Tony Lefebvre
Fatty Acid Synthase (FASN) is a central enzyme in the de novo lipogenesis pathway. By producing fatty acids, FASN is implicated in numerous crucial cellular processes, but it is also frequently overexpressed in cancer. O-GlcNAc Transferase (OGT) governs the addition of N-acetylglucosamine residues onto cytosolic, nuclear and mitochondrial proteins. Like FASN, OGT actively participates in carcinogenesis. We previously showed that OGT regulates FASN in different ex vivo and in vivo models. Reciprocally, FASN promotes OGT expression and activity. The two enzymes physically interact together and contribute to cancer cell survival. It is therefore fundamental to define the respective interaction region of each enzyme to explore new therapeutic solutions for patients suffering from cancer. By using the hepatocarcinoma cell line Hep3B, we show thanks to two series of deletion mutants that both enzymes preferentially interact via their respective N-terminal regions. Analysis of the O-GlcNAc status of the various FASN deletion mutants shows that stronger interaction with OGT correlates with higher glycosylation, suggesting that OGT catalyzes the transfer of GlcNAc with limited substrate specificity.
脂肪酸合成酶(FASN)是新生脂肪生成途径中的中心酶。通过产生脂肪酸,FASN参与了许多关键的细胞过程,但它也经常在癌症中过度表达。O-GlcNAc转移酶(OGT)控制n -乙酰氨基葡萄糖残基在细胞质、核和线粒体蛋白上的添加。与FASN一样,OGT也积极参与致癌作用。我们之前的研究表明,在不同的离体和体内模型中,OGT调节FASN。反过来,FASN促进OGT的表达和活性。这两种酶相互作用,促进癌细胞存活。因此,确定每种酶各自的相互作用区域对于探索癌症患者的新治疗方案至关重要。通过使用肝癌细胞系Hep3B,我们发现由于两个系列的缺失突变,这两种酶都优先通过各自的n端区域相互作用。对各种FASN缺失突变体O-GlcNAc状态的分析表明,与OGT的相互作用越强,糖基化程度越高,表明OGT催化GlcNAc转移的底物特异性有限。
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引用次数: 0
Humanin improves bone health in a glucocorticoid-treated mouse model of Duchenne muscular dystrophy 人源素改善糖皮质激素治疗的杜氏肌营养不良小鼠模型的骨骼健康
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102421
Therése Cedervall , Baptiste Jude , Ferdinand von Walden , Lilly Velentza , Johanna T. Lanner , Thomas Sejersen , Farasat Zaman , Lars Sävendahl
Duchenne muscular dystrophy (DMD) is a progressive muscle disease for which glucocorticoid (GC) treatment is standard therapy. Patients typically suffer from short stature and osteoporosis, caused by the underlying disease and adverse effects of GCs. We investigated whether the mitochondrial peptide humanin (HNG) could prevent GC-induced growth retardation and osteoporosis in mouse models of DMD.
Male mdx mice (B10.mdx and D2.mdx) were treated with GCs, with/without HNG, from 5 to 9 weeks of age using two different treatment regimens. Tibial growth was monitored by weekly X-ray imaging; growth plates analyzed with immunohistochemistry and histomorphometry; and bone structure examined using peripheral quantitative computed tomography. Effects on skeletal muscle were evaluated by immunohistochemistry, qPCR, and ex vivo force measurements.
D2.mdx, but not B10.mdx, showed decreased bone growth and impaired bone structure compared with wild type (WT). D2.mdx also displayed increased growth plate height with lower endogenous humanin expression than D2.WT. GC treatment caused growth retardation and reductions in cortical bone area, thickness, and mineral content. Co-administration with HNG prevented bone growth impairment at one week of treatment and mitigated GC adverse effects on cortical bone in B10.mdx mice. Adding HNG to GCs did not exacerbate skeletal muscle pathology; in fact, HNG had a mild enlarging effect on muscle fibers.
These data suggest that HNG is a potential candidate for improving bone health in DMD during GC therapy. Further in vivo studies are needed to determine optimal HNG dosing and to assess the effects of long-term treatment on skeletal muscle function.
杜氏肌营养不良症(DMD)是一种进行性肌肉疾病,糖皮质激素(GC)治疗是标准治疗方法。患者通常患有矮小和骨质疏松症,这是由潜在疾病和GCs的不良反应引起的。我们研究了线粒体肽humanin (HNG)是否能预防gc诱导的DMD小鼠模型的生长迟缓和骨质疏松。雄性mdx小鼠(B10;mdx和D2。mdx)在5 - 9周龄期间使用两种不同的治疗方案,分别使用GCs(含/不含HNG)进行治疗。每周x线检查胫骨生长情况;用免疫组织化学和组织形态学分析生长板;用外围定量计算机断层扫描检查骨结构。通过免疫组织化学、qPCR和离体力测量来评估对骨骼肌的影响。mdx,但不是B10。与野生型(WT)相比,mdx表现出骨生长减少和骨结构受损。D2。mdx的生长板高度也比D2.WT高,内源人蛋白表达量较低。GC处理导致生长迟缓和皮质骨面积、厚度和矿物质含量减少。与HNG共给药可在治疗一周后防止骨生长损伤,并减轻GC对B10皮质骨的不良影响。mdx老鼠。在GCs中加入HNG不会加重骨骼肌病理;事实上,HNG对肌纤维有轻微的扩大作用。这些数据表明,在GC治疗期间,HNG是改善DMD患者骨骼健康的潜在候选者。需要进一步的体内研究来确定最佳的HNG剂量,并评估长期治疗对骨骼肌功能的影响。
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引用次数: 0
Melatonin alleviates gentamicin-induced acute kidney injury through the Keap1/Nrf2/HO-1 signaling pathway 褪黑素通过Keap1/Nrf2/HO-1信号通路减轻庆大霉素诱导的急性肾损伤
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102433
Ningning Li , Xianghua Liu , Wei Liu , Saifei Li , Yanfei Lei , Baoying Wang
Drug-related factors represent a primary cause of acute kidney injury. Gentamicin (GM), while being one of the most effective and commonly used clinical agents against Gram-negative bacteria, frequently induces nephrotoxicity and triggers acute kidney injury during treatment. Melatonin, a natural antioxidant produced by the pineal gland, has been shown in recent studies to mitigate drug-induced nephrotoxicity. This study aimed to delineate the dose-dependent effects and underlying mechanisms of GM-induced acute kidney injury, along with the protective role of melatonin. Results demonstrated that GM administration elicited dose-dependent nephrotoxicity in rats, significantly elevating urinary biomarkers of tubular injury (KIM-1 and NGAL) and serum markers of renal dysfunction (BUN and SCr) at doses ≥50 mg/kg. Histopathological analysis revealed progressive renal damage including brush border loss, epithelial necrosis, basement membrane disruption, and interstitial inflammation. GM further exacerbated renal oxidative stress, depleting SOD and GSH while elevating MDA levels. Mechanistically, GM dose-dependently upregulated Keap1 and downregulated NRF2 expressions, consequently suppressing downstream antioxidants (GPX1, NQO1, HO-1). However, melatonin treatment significantly ameliorated high-dose GM-induced acute kidney injury by normalizing biochemical markers of renal impairment, attenuating histopathological damage, restoring antioxidant capacity, and reactivating the KEAP1/NRF2 pathway through suppression of Keap1 while enhancing NRF2 and its target proteins (GPX1/NQO1/HO-1) to nearly double of GM-H group levels, confirming its renoprotective role against GM-induced oxidative injury.
药物相关因素是急性肾损伤的主要原因。庆大霉素(genamicin, GM)是临床最有效和常用的抗革兰氏阴性菌药物之一,但在治疗过程中经常引起肾毒性和急性肾损伤。褪黑素是一种由松果体产生的天然抗氧化剂,在最近的研究中显示可以减轻药物引起的肾毒性。本研究旨在描述转基因诱导的急性肾损伤的剂量依赖性效应和潜在机制,以及褪黑激素的保护作用。结果表明,在剂量≥50 mg/kg时,转基因给药引起大鼠剂量依赖性肾毒性,显著升高尿小管损伤生物标志物(KIM-1和NGAL)和血清肾功能障碍标志物(BUN和SCr)。组织病理学分析显示进行性肾损害包括肾刷缘丢失、上皮坏死、基底膜破坏和间质炎症。转基因进一步加重了肾脏氧化应激,使SOD和GSH消耗,同时使MDA水平升高。在机制上,GM剂量依赖性地上调Keap1和下调NRF2表达,从而抑制下游抗氧化剂(GPX1, NQO1, HO-1)。然而,褪黑素治疗显著改善了高剂量gm诱导的急性肾损伤,通过使肾损害的生化标志物正常化,减轻组织病理损伤,恢复抗氧化能力,并通过抑制KEAP1重新激活KEAP1/NRF2途径,同时使NRF2及其靶蛋白(GPX1/NQO1/HO-1)水平提高到GM-H组的近两倍,证实了其对gm诱导的氧化损伤的肾保护作用。
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引用次数: 0
Normal spermatogenesis and fertility in Spmip8 deficiency male mice Spmip8缺陷雄性小鼠的正常精子发生和生育能力
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102406
Zeling Zhang , Meihong Hu , Di Yan, Yuanqi Zhao, Wen Tao, Shengyuan Chen, Meijie Qi, Lei Luo, Xiaohua Jiang, Bo Xu, Shun Bai
Spmip8, also known as Tepp, is a protein-coding gene which highly conserved in the mammals. Although SPMIP8 has been reported to be highly expressed in the testis, the function of SPMIP8 in spermatogenesis and male fertility remain unknown. In this study, we used CRISPR/cas9-mediated genome editing system to generate Spmip8-deficient mice. The phenotype of Spmip8 knockout (KO) male mice was performed by fertility tests, histology, and immunofluorescence. SPMIP8 is localization to the flagella of elongating spermatids in testis. Spmip8 KO male mice exhibited normal fertility. No significant differences were found in sperm count, motility, morphology and kinematic parameters between WT and Spmip8 KO mice. Furthermore, no detectable defects in spermatogenesis were found in KO mice. The transcription level of several Spmip genes (Spmip1, Spmip2, Spmip3, Spmip7 and Spmip11) was elevated in the testes of Spmip8 knockout mice, suggesting that Spmip8 gene in male fertility could be compensated by other Spmip family members. Overall, the findings of this study suggest that Spmip8 is not an essential gene for male fertility in mice. Our study helps researchers avoid duplication and repetitive work and explore genes that are integral to spermatogenesis and male fertility.
Spmip8,又称Tepp,是一种在哺乳动物中高度保守的蛋白质编码基因。尽管SPMIP8已被报道在睾丸中高表达,但SPMIP8在精子发生和男性生育中的功能尚不清楚。在本研究中,我们使用CRISPR/cas9介导的基因组编辑系统生成spmip8缺陷小鼠。通过生育试验、组织学和免疫荧光检测Spmip8基因敲除(KO)雄性小鼠的表型。SPMIP8定位于睾丸中细长精子的鞭毛。Spmip8 KO雄性小鼠表现出正常的生育能力。在精子数量、活力、形态和运动学参数方面,WT和Spmip8 KO小鼠无显著差异。此外,在KO小鼠中未发现可检测到的精子发生缺陷。Spmip8基因敲除小鼠睾丸中多个Spmip基因(Spmip1、Spmip2、Spmip3、Spmip7和Spmip11)的转录水平升高,提示Spmip8基因在雄性生育能力中的作用可以通过Spmip8家族其他成员来弥补。总的来说,本研究的结果表明,Spmip8不是小鼠雄性生育能力的必要基因。我们的研究帮助研究人员避免重复和重复的工作,并探索对精子发生和男性生育能力不可或缺的基因。
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引用次数: 0
Functional classification of antineutrophil cytoplasmic antibody (ANCA) and its relation with clinical parameters of ANCA-associated vasculitis 抗中性粒细胞胞浆抗体(ANCA)的功能分类及其与ANCA相关性血管炎临床参数的关系
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.bbrep.2025.102428
Mai Taniguchi , China Washio , Momo Uchizawa , Naho Ogawa , Riku Manabe , Suishin Arai , Hodaka Ogawa , Yuka Nishibata , Sakiko Masuda , Daigo Nakazawa , Utano Tomaru , Yoshihiro Arimura , Koichi Amano , Yukio Yuzawa , Ken-Ei Sada , Tatsuya Atsumi , Hiroaki Dobashi , Masayoshi Harigai , Seiichi Matsuo , Hirofumi Makino , Akihiro Ishizu
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by serum ANCA and systemic small-vessel vasculitis. Neutrophils are primed to express ANCA antigens on the plasma membrane. ANCA binding to the antigens can transduce signals into neutrophils, releasing reactive oxygen species (ROS) and contributing to AAV development. ANCA-mediated signals are transduced via two pathways: ANCA antigens crosslinked by ANCA, and Fcγ receptor (FcγR), to which the Fc portion of ANCA binds. This study aimed to demonstrate the association of ANCA-mediated neutrophil activation pathways with clinical manifestations of AAV, including renal dysfunction and kidney survival at 6 months after treatment. For this purpose, IgG was extracted from the serum of AAV patients before treatment (n = 112), and ROS production from neutrophils exposed to IgG and its suppression by FcγR inhibitors (FcX) were assessed. IgG exhibiting higher ROS production than control IgG was classified as ROS-inducing ANCA and the others as ROS-noninducing ANCA. The former was subclassified into antigen-driven ANCA and FcγR-driven ANCA according to whether the ROS production suppression rate by FcX was <50 % or ≧50 %, respectively. As a result, ANCA was classified into ROS-inducing antigen-driven ANCA (n = 74), ROS-inducing FcγR-driven ANCA (n = 22), and ROS-noninducing ANCA (n = 16). Serum levels of blood urea nitrogen and creatinine were significantly higher in patients with ROS-inducing FcγR-driven ANCA than in those with ROS-noninducing ANCA. Patients with ROS-inducing FcγR-driven ANCA had a significantly lower kidney survival rate 6 months after treatment than other patients. The collective findings suggest that ROS-inducing FcγR-driven ANCA may predict poor kidney prognosis in AAV.
抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV)以血清ANCA和全身小血管炎为特征。中性粒细胞被诱导在质膜上表达ANCA抗原。与抗原结合的ANCA可以将信号传递到中性粒细胞,释放活性氧(ROS),促进AAV的发展。ANCA介导的信号通过两条途径转导:ANCA交联的ANCA抗原和ANCA的Fcγ受体(Fcγ r), ANCA的Fc部分与之结合。本研究旨在证明anca介导的中性粒细胞激活途径与AAV临床表现的相关性,包括治疗后6个月的肾功能障碍和肾存活。为此,在治疗前从AAV患者的血清中提取IgG (n = 112),并评估暴露于IgG的中性粒细胞产生ROS及其被FcγR抑制剂(FcX)抑制的情况。产生ROS量高于对照IgG的IgG被归类为诱导ROS的ANCA,其他IgG被归类为不诱导ROS的ANCA。根据FcX对活性氧产生的抑制率是否为50 %或≧50 %,将前者分为抗原驱动型ANCA和fc γ r驱动型ANCA。将ANCA分为诱导ros的抗原驱动ANCA (n = 74)、诱导ros的fc γ r驱动ANCA (n = 22)和非诱导ros的ANCA (n = 16)。ros诱导型fc - γ - r驱动型ANCA患者血清尿素氮和肌酐水平明显高于非ros诱导型ANCA患者。ros诱导的fc γ r驱动的ANCA患者在治疗后6个月的肾脏存活率明显低于其他患者。综上所述,ros诱导的fc - γ - r驱动的ANCA可能预测AAV患者肾脏预后不良。
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