Prostaglandins & other lipid mediators最新文献_第2页

Revealing the biochemical regulations of L-PGDS in hepatic insulin-resistance using HepG2 cells 利用HepG2细胞揭示L-PGDS在肝脏胰岛素抵抗中的生化调节作用

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-12-10 DOI: 10.1016/j.prostaglandins.2025.107052

Rhema Khairnar, Md Asrarul Islam, Kuljeet Singh, Divya K. Shetty, Anjali Yadav, Vikas V. Dukhande, Sunil Kumar

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its prevalence poses a serious health threat globally. MASLD is a multifactorial hepatic disorder, but insulin resistance is a key player. Our prior in vivo studies revealed that the absence of lipocalin prostaglandin D₂ synthase (L-PGDS) leads to the development of MASLD, often coexisting with insulin resistance. Briefly, L-PGDS belongs to the arachidonic acid pathway and enzymatically catalyzes the conversion of prostaglandin H₂ to prostaglandin D_2, which imparts physiological effects via DP1 and DP2 receptors. L-PGDS plays a crucial role in MASLD; however, its mechanistic regulation remains unexplored. Therefore, we aimed to study the biochemical regulation of L-PGDS using a cellular model of MASLD. We successfully recapitulated the MASLD phenotype in HepG2 cells by co-treating with palmitate and insulin. Our results showed significant downregulation of L-PGDS and decreased PGD₂ levels in an insulin-resistant state. To study this L-PGDS downregulation, we employed MG132, chloroquine, cycloheximide, and immunoprecipitation to assess proteasomal degradation, autophagy, translational activity, and ubiquitination, respectively. However, the above pathways were not involved. Interestingly, gene and protein expression results revealed the clues for L-PGDS downregulation, showing significantly decreased transcription and subsequently protein levels. Additionally, subcellular localization results showed that insulin resistance induced the trafficking of L-PGDS from the cytoplasm to the nucleus. In summary, L-PGDS downregulation possibly involves transcription-translation and/or subcellular localization pathways. However, further studies are required to delineate the molecular mechanism of L-PGDS downregulation and apply this knowledge to MASLD pathogenesis and treatment.

代谢功能障碍相关脂肪变性肝病（MASLD）是最常见的慢性肝病，其患病率在全球范围内构成严重的健康威胁。MASLD是一种多因素肝病，但胰岛素抵抗是关键因素。我们之前的体内研究表明，脂钙素前列腺素D2合成酶（L-PGDS）的缺乏导致MASLD的发展，通常与胰岛素抵抗共存。简而言之，L-PGDS属于花生四烯酸途径，酶促前列腺素H2转化为前列腺素D2，并通过DP1和DP2受体发挥生理作用。L-PGDS在MASLD中起重要作用；然而，其机制调控仍未被探索。因此，我们旨在利用MASLD细胞模型研究L-PGDS的生化调控。通过棕榈酸盐和胰岛素的共同作用，我们成功地再现了HepG2细胞的MASLD表型。我们的研究结果显示，胰岛素抵抗状态下，L-PGDS显著下调，PGD2水平降低。为了研究这种L-PGDS的下调，我们分别使用MG132、氯喹、环己亚胺和免疫沉淀来评估蛋白酶体降解、自噬、翻译活性和泛素化。但上述途径均未涉及。有趣的是，基因和蛋白表达结果揭示了L-PGDS下调的线索，显示转录和随后的蛋白水平显著降低。此外，亚细胞定位结果显示，胰岛素抵抗诱导L-PGDS从细胞质转运到细胞核。总之，L-PGDS下调可能涉及转录-翻译和/或亚细胞定位途径。然而，需要进一步的研究来描述L-PGDS下调的分子机制，并将这些知识应用于MASLD的发病机制和治疗。

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引用次数: 0

The association of Cytochrome 4F2 rs2108622 genetic variant and non-genetic factors with essential hypertension among Jordanian patients attending the University of Jordan Hospital 在约旦大学医院就诊的约旦患者中，细胞色素4F2 rs2108622遗传变异和非遗传因素与原发性高血压的关系

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-12-01 DOI: 10.1016/j.prostaglandins.2025.107045

Enas Yousef Alkasasbeh , Yazun Bashir Jarrar , Wiam Khalil , Hussein Alhawari , Malek Zihlif

Background

Essential hypertension (EH) contributes to death and morbidity. CYP4 genes influence EH via 20-hydroxyeicosatetraenoic acid production. Identifying genetic risk factors may reveal biomarkers for EH among Jordanian patients.

Aim

To determine the prevalence of CYP4F2 rs2108622 genetic variants, determine their influence on the systolic (SBP) and diastolic blood pressure (DBP), and their association with the risk of EH disease among Jordanian patients.

Methods

This case-control study consisted of 200 Jordanian individuals recruited from Jordan University Hospital, divided into two groups: 100 hypertensive patients (cases) and 100 non-hypertensive individuals (controls). The data for demographic, anthropometric, blood pressure measurements, glycaemic, and lipid profile measurements were collected from participants during their hospital visits and from the hospital’s computer’s record. The genotyping of CYP4F2 rs2108622 genetic variant was done using PCR-RFLP.

Results

EH patients had a significantly higher mean age (45.82 ± 10.6 years, P < 0.001) and BMI (30.84 ± 5.27 kg/m², P = 0.001) compared to controls. Obesity was significantly associated with EH (OR = 3.18, P = 0.01). The CT genotype of CYP4F2 rs2108622 was more frequent among EH patients (79 %) than controls (66 %) (P < 0.001) and was associated with increased EH risk (CT vs TT: OR = 3.02, P = 0.01; CT vs CC: OR = 2.71, P = 0.025). Genotype variations also showed significant associations with SBP (P = 0.019) and DBP (P = 0.017).

Conclusion

It can be concluded from this study that age, BMI and heterozygous CYP4F2 rs2108622 genotype are significantly associated with the occurrence of EH among Jordanians. The CYP4F2 rs2108622 genotype can be considered as a potential candidate biomarker of the development of EH. However, more studies with larger sample size are needed to validate the finding of this study.

背景：原发性高血压（EH）会导致死亡和发病。CYP4基因通过产生20-羟基二碳四烯酸影响EH。确定遗传风险因素可能揭示约旦患者EH的生物标志物。目的：确定CYP4F2 rs2108622基因变异的患病率，确定其对收缩压（SBP）和舒张压（DBP）的影响，以及它们与约旦患者EH疾病风险的关系。方法：本病例对照研究从约旦大学医院招募200名约旦人，分为两组：100名高血压患者（病例）和100名非高血压患者（对照组）。人口统计、人体测量、血压测量、血糖和脂质测量数据是在参与者就诊期间和医院电脑记录中收集的。采用PCR-RFLP方法对CYP4F2 rs2108622基因变异进行分型。结果：EH患者的平均年龄显著增高（45.82 ± 10.6岁，P ）。结论：本研究得出年龄、BMI和杂合CYP4F2 rs2108622基因型与约旦人EH的发生显著相关。CYP4F2 rs2108622基因型可以被认为是EH发展的潜在候选生物标志物。然而，需要更多更大样本量的研究来验证本研究的发现。

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引用次数: 0

Lipocalin-type prostaglandin D₂ synthase (L-PGDS) deficiency disrupts heme catabolism and iron homeostasis in mice 脂钙素型前列腺素D 2合成酶（L-PGDS）缺乏会破坏小鼠血红素分解代谢和铁稳态

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-11-20 DOI: 10.1016/j.prostaglandins.2025.107046

Matthew Stevenson, Bryan Chen, Ankita Srivastava, Christopher E. Hall, Louis Ragolia

Efficient recycling of red blood cells (RBCs) requires not only heme cleavage but also stabilization of reactive intermediates generated during iron liberation. Lipocalin-type Prostaglandin D₂ Synthase (L-PGDS, β-trace protein), best known for prostaglandin synthesis, possesses structural and biochemical features consistent with a buffering role in heme catabolism. Here, we show that L-PGDS knockout mice exhibit elevated plasma, increased total splenic iron, reduced total hepatic iron, decreased plasma free heme/hemin, and modest RBC enlargement, consistent with disrupted iron release. Transcript–protein mismatches in key iron regulators, including NRF2 and FPN, further suggest redox imbalance and impaired iron sensing. Despite normal Hmox1 expression, these mice display widespread evidence of inefficient porphyrin clearance. Combined with prior findings that L-PGDS binds ferric biliverdin and is upregulated during heme overload, our results support a model in which L-PGDS buffers porphyrin intermediates to facilitate their safe processing and clearance. This study identifies L-PGDS as a putative auxiliary factor in heme catabolism, with implications for iron recycling, erythropoiesis, and systemic iron homeostasis. All data in this report are from male mice.

红细胞（rbc）的有效循环不仅需要血红素的裂解，还需要铁释放过程中产生的活性中间体的稳定。脂钙素型前列腺素D₂合成酶（Lipocalin-type Prostaglandin D₂Synthase, L-PGDS， β-微量蛋白）以前列腺素合成而闻名，其结构和生化特征与血红素分解代谢的缓冲作用一致。在这里，我们发现L-PGDS敲除小鼠表现出血浆升高，总脾铁增加，总肝铁减少，血浆游离血红素/血红素减少，红细胞适度增大，与铁释放中断一致。包括NRF2和FPN在内的关键铁调节因子的转录蛋白错配进一步表明氧化还原失衡和铁感知受损。尽管Hmox1表达正常，但这些小鼠普遍表现出卟啉清除效率低下的证据。结合先前的研究结果，L-PGDS结合铁胆汁素并在血红素超载时上调，我们的研究结果支持了L-PGDS缓冲卟啉中间体以促进其安全加工和清除的模型。本研究确定L-PGDS可能是血红素分解代谢的辅助因子，与铁循环、红细胞生成和全身铁稳态有关。本报告所有数据均来自雄性小鼠。

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引用次数: 0

Pro-inflammatory differentiation by GM-CSF reduces prostanoid release and phagocytic activity in murine bone marrow-derived macrophages GM-CSF的促炎分化降低小鼠骨髓源性巨噬细胞的前列腺素释放和吞噬活性。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-11-19 DOI: 10.1016/j.prostaglandins.2025.107044

Jianyang Liu , Helena Idborg , Marina Korotkova , Per-Johan Jakobsson

Murine bone marrow-derived macrophages (BMDMs) are widely used to study macrophage functions in vitro. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are routinely used to differentiate monocytes into M1- and M2-like macrophages, respectively. Although macrophage-derived eicosanoids regulate both inflammation and its resolution, the impact of these differentiation factors on eicosanoid production remains poorly understood. Additionally, eicosanoid secretion and transportation has never been characterised in these macrophage populations. In the present study, we show that BMDMs differentiated in the presence of GM-CSF (hereafter referred to as GM-BMDMs) produce markedly lower levels of arachidonic acid (AA)-derived prostanoids following lipopolysaccharide (LPS) activation than macrophages differentiated with M-CSF (hereafter referred to as M-BMDMs). Moreover, we found that GM-BMDMs failed to rapidly release LPS-induced prostanoids. Mechanistically, this delayed release of prostanoids likely arises from reduced expression of the prostaglandin efflux transporter multidrug resistance protein-4 (MRP4) alongside a concomitant upregulation of the influx prostaglandin transporter (PGT). Our results also highlight that analyses of both cell pellets and supernatants are essential when comparing oxylipin profiles between M1- and M2-like macrophages. We next studied the phagocytic capacity of GM-BMDMs and found that GM-BMDMs display a blunted increase in phagocytosis of fluorescent E. coli bioparticles after LPS stimulation compared to M-BMDMs. Pharmacological inhibition of microsomal prostaglandin E synthase-1 (mPGES-1), but not cyclooxygenase-2 (COX-2), promotes phagocytic capacity, suggesting that mPGES-1 inhibitors may be superior to COX-2 inhibitors for suppressing inflammation. Collectively, our findings reveal that GM-CSF not only modulates the production and trafficking of prostanoids but also constrains phagocytic activity in response to LPS, which can be enhanced by mPGES-1 inhibition.

小鼠骨髓源性巨噬细胞（bmdm）被广泛用于体外巨噬细胞功能的研究。粒细胞-巨噬细胞集落刺激因子（GM-CSF）和巨噬细胞集落刺激因子（M-CSF）通常分别用于将单核细胞分化为M1样和m2样巨噬细胞。尽管巨噬细胞衍生的类二十烷醇调节炎症及其消退，但这些分化因子对类二十烷醇产生的影响仍知之甚少。此外，在这些巨噬细胞群体中，类二十烷酸的分泌和运输从未被表征。在本研究中，我们发现在GM-CSF存在下分化的BMDMs（以下简称GM-BMDMs）在脂多糖（LPS）激活后产生的花生四烯酸（AA）衍生的前列腺素水平明显低于用M-CSF分化的巨噬细胞（以下简称M-BMDMs）。此外，我们发现gm - bmdm不能快速释放lps诱导的前列腺素。从机制上讲，这种前列腺素的延迟释放可能是由于前列腺素外排转运体多药耐药蛋白-4 （MRP4）的表达减少以及前列腺素内流转运体（PGT）的上调。我们的研究结果还强调，在比较M1和m2样巨噬细胞之间的氧脂质谱时，细胞颗粒和上清液的分析是必不可少的。接下来，我们研究了GM-BMDMs的吞噬能力，发现与M-BMDMs相比，在LPS刺激后，GM-BMDMs对荧光大肠杆菌生物颗粒的吞噬能力增加减弱。药物抑制微粒体前列腺素E合成酶-1 (mPGES-1)，而不是环氧化酶-2 (COX-2)，恢复吞噬能力，表明mPGES-1抑制剂可能优于COX-2抑制剂抑制炎症。总之，我们的研究结果表明，GM-CSF不仅调节前列腺素的产生和运输，而且还抑制LPS对吞噬活性的反应，这可以通过抑制mPGES-1来增强。

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引用次数: 0

Impact of overexpression of wild-type CFTR and elexacaftor-tezacaftor-ivacaftor on oxylipin production by the CFBE41o- bronchial epithelial cell line 过表达野生型CFTR和elexacafter - tezacafter - ivacaftor对cfbe410 -支气管上皮细胞产生氧化脂素的影响

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-11-08 DOI: 10.1016/j.prostaglandins.2025.107043

Dustin G. Brown , Jonathan Manke , Michael Armstrong , Sangya Yadav , John O. Marentette , James R. Roede , Eszter K. Vladar , Nichole Reisdorph , Vanessa V. Phelan

A hallmark of cystic fibrosis (CF) is dysregulated lipid metabolism marked by an imbalance of pro-inflammatory to pro-resolving metabolites. Despite the breadth of evidence associating mutation of the cystic fibrosis conductance regulator (CFTR) with dysregulation of the production of oxylipins, oxidized lipid mediators with specialized functions generated during inflammation, few studies have directly measured whether overexpression of wild-type (WT) CFTR is sufficient to equilibrate oxylipin levels in CF models. In this study, targeted lipidomics was used to compare the oxylipin profiles of the parental CFBE41o- immortalized bronchial epithelial cell line homozygous for F508del CFTR, the most common CFTR mutation in people with CF, with the same cell line overexpressing WT CFTR (CFBE41o- o/e WT CFTR). Overexpression of WT CFTR in the CFBE41o- background resulted in decreased production of prostaglandins and increased production of precursors of specialized pro-resolving mediators, including 14,15-epoxyeicosatrienoic acid (14(15)-EET) compared to the parent CFBE41o- cell line, likely due to a decrease in production of inducible COX-2 associated with inflammation and an increase in COX-1 and PPARγ associated with resolution of inflammation. Additionally, highly effective modulator therapy (HEMT) improves pulmonary health for people with CF (PwCF) by targeting the underlying biochemical dysfunction of mutant CFTR. However, its impact on dysregulated lipid metabolism remains under-investigated. Despite inducing production and trafficking of F508del CFTR, treatment of the CFBE41o- parental cell line monolayers with the HEMT elexacaftor-tezacaftor-ivacaftor (ETI) increased levels of the prostaglandin E2 (PGE₂). This disparity in cellular response by CFBE41o- cells to overexpression of WT CFTR and exposure to ETI was due to differences in production of prostaglandin biosynthetic and regulatory proteins upstream of oxylipin biosynthesis.

囊性纤维化（CF）的一个标志是脂质代谢失调，其特征是促炎代谢产物与促溶解代谢产物的不平衡。尽管有大量证据表明囊性纤维化传导调节因子（CFTR）的突变与炎症过程中氧化脂质介质氧化脂质产生失调有关，但很少有研究直接测量CF模型中野生型CFTR的过表达是否足以平衡氧化脂质水平。本研究采用靶向脂质组学方法，将CF患者中最常见的CFTR突变F508del CFTR的亲本cfbe410 -永生化支气管上皮细胞系与过表达WT CFTR的同一细胞系（cfbe410 - o/e WT CFTR）的氧脂质谱进行了比较。与亲本cfbe410 -细胞系相比，cfbe410 -背景下WT CFTR的过表达导致前列腺素的产生减少，特殊促溶解介质前体的产生增加，包括14,15-环氧二碳三烯酸（14(15)- eet），可能是由于与炎症相关的诱导COX-2的产生减少，以及与炎症消退相关的COX-1和PPARγ的增加。此外，高效调节疗法（HEMT）通过靶向CFTR突变体潜在的生化功能障碍，改善CF （PwCF）患者的肺部健康。然而，其对脂质代谢失调的影响仍未得到充分研究。尽管诱导了F508del CFTR的产生和运输，但HEMT萃取因子-活化因子-激活因子（ETI）处理cfbe410亲本细胞系单层后，前列腺素E2 （PGE2）水平升高。cfbe410 -细胞对WT CFTR过表达和ETI暴露的细胞反应差异是由于前列腺素生物合成和氧化脂素生物合成上游调节蛋白的产生差异。

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引用次数: 0

The role of eicosapentaenoic acid-loaded nanoparticles on alleviating drug resistance in xenograft breast cancer model 载二十碳五烯酸纳米颗粒在减轻异种移植乳腺癌模型耐药中的作用

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-10-22 DOI: 10.1016/j.prostaglandins.2025.107042

Fatma F. Elsayed , Dina M. Abo-elmatty , Zakaria El -khayat , Emad Tolba , Alaa S. Wahba , Jihan Hussien

Background

Multidrug resistance (MDR) is a major dilemma in the effective chemotherapy treatment of breast cancer. Potential strategies to combat MDR include inhibiting efflux pumps such as ATP-binding cassette (ABC) transporters and calcium channel pumps like transient receptor potential (TRP) channels and blocking the metastatic pathway by inhibiting the antiapoptotic proteins like Bcl-2, while enhancing the apoptotic proteins like caspase-3.

Results

The results demonstrated that treatment with either EPA or EPA/PCL led to a marked suppression of doxorubicin resistance, as evidenced by a significant reduction in tumor size, measured by caliper, in the treated groups over the course of the experiment. Furthermore, the combination of EPA or EPA-loaded PCL with DOX modulated the expression of drug resistance genes and apoptotic pathways by targeting transient receptor potential canonical 5 (TRPC5), P-glycoprotein (P-gp), and Bcl-2, while simultaneously enhancing the expression of caspase-3. Additionally, nano-characterization of the PCL particles using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis demonstrated their favorable stability and physicochemical properties.

Conclusion

The present study investigated the effect of eicosapentaenoic acid (EPA)-loaded polycaprolactone (PCL) in overcoming drug resistance when used in combination with doxorubicin (DOX), as compared to DOX alone and EPA in its original form. Interestingly, it reveals a promising approach to ameliorate the resistance of Doxorubicin in breast cancer.

背景：多药耐药（MDR）是影响乳腺癌有效化疗的主要难题。对抗MDR的潜在策略包括抑制外流泵（如atp结合盒（ABC）转运体）和钙通道泵（如瞬时受体电位（TRP）通道），以及通过抑制抗凋亡蛋白如Bcl-2来阻断转移途径，同时增强凋亡蛋白如caspase-3。结果表明，EPA或EPA/PCL治疗导致阿霉素耐药性的显著抑制，在实验过程中，治疗组的肿瘤大小显着减少（用卡尺测量）。此外，EPA或EPA负载PCL与DOX联合可通过靶向瞬时受体电位规范5 （TRPC5）、p -糖蛋白（P-gp）和Bcl-2调控耐药基因的表达和凋亡通路，同时增强caspase-3的表达。此外，利用透射电子显微镜（TEM）、动态光散射（DLS）和zeta电位分析对PCL颗粒进行了纳米表征，表明其具有良好的稳定性和理化性质。结论本研究考察了负载二十碳五烯酸（EPA）的聚己内酯（PCL）与多柔比星（DOX）联合使用时克服耐药的效果，并与单独使用DOX和原始形式的EPA进行了比较。有趣的是，它揭示了一种有希望的方法来改善多柔比星在乳腺癌中的耐药性。

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引用次数: 0

Prostaglandin E2 is a crucial intermediator of 17β-estradiol-induced growth factor expression in bovine endometrial cells and explants 前列腺素E2是牛子宫内膜细胞和外植体中17β-雌二醇诱导的生长因子表达的重要中介

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-10-02 DOI: 10.1016/j.prostaglandins.2025.107041

Wenhui Bao , Shuangyi Zhang , Jiamin Zhao , Zhiguo Gong , Yunjie Bai , Yanqin Dong , Wei Mao , Bo Liu

Estradiol is a critical hormone that regulates morphological and functional changes in the bovine endometrium throughout the estrous cycle. Prostaglandin E₂ (PGE₂), a well-established inflammatory mediator, also plays an essential role in endometrial physiology. Whether PGE₂ acts as an intermediary in estradiol-related activities within the bovine endometrium remains unclear. The results revealed that 17β-estradiol at 10⁻¹⁰ M and 10⁻⁹ M induced PGE₂ secretion in endometrial explants, whereas a higher concentration (10⁻⁷ M) downregulated PGE₂ secretion. In endometrial epithelial cells, 17β-estradiol at concentrations ranging from 10⁻¹⁰ to 10⁻⁸ M stimulated PGE₂ secretion. In endometrial stromal cells, 17β-estradiol at 10⁻¹⁰ to 10⁻⁷ M concentrations promoted PGE₂ production. PGE₂ synthesis was inhibited by the mPGES-1 inhibitor MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl) isophthalonitrile] in the presence of 17β-estradiol (10⁻⁹ M), highlighting mPGES-1 as a key enzyme in 17β-estradiol-induced PGE₂ production in the bovine endometrium. Furthermore, both the mRNA and protein levels of endometrial growth factors, including fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2 (MMP-2), and MMP-9, were increased by 17β-estradiol (10⁻⁹ M). This effect was reversed by pretreatment with the mPGES-1 inhibitor MF63 in endometrial cells and explants. Notably, supplementation with exogenous PGE₂ restored the expression of these growth factors in the presence of both 17β-estradiol (10⁻⁹ M) and MF63. In conclusion, mPGES-1-derived PGE₂ serves as a crucial mediator of the 17β-estradiol-induced expression of FGF-2, VEGFA, MMP-2, and MMP-9 in the bovine endometrium, underscoring its significant role in regulating endometrial function.

雌二醇是在整个发情周期中调节牛子宫内膜形态和功能变化的关键激素。前列腺素E2 （PGE2）是一种公认的炎症介质，在子宫内膜生理学中也起着重要作用。PGE2是否在牛子宫内膜中作为雌二醇相关活动的中介仍不清楚。结果表明，在10−10 M和10−9 M浓度下，17β-雌二醇可诱导子宫内膜外植体分泌PGE2，而在10−7 M浓度下，PGE2的分泌会下调。在子宫内膜上皮细胞中，17β-雌二醇浓度在10−10 ~ 10−8 M范围内刺激PGE2分泌。在子宫内膜基质细胞中，10 - 10至10 - 7 M浓度的17β-雌二醇促进了PGE2的产生。在17β-雌二醇（10−9 M）存在下，mPGES-1抑制剂MF63[2-（6-氯- 1h -菲菲罗[9,10-d]咪唑-2-基）异苯二腈]抑制了PGE2的合成，表明mPGES-1是17β-雌二醇诱导的牛子宫内膜PGE2生成的关键酶。此外，17β-雌二醇（10−9 M）增加了子宫内膜生长因子mRNA和蛋白水平，包括成纤维细胞生长因子2 （FGF-2）、血管内皮生长因子A （VEGFA）、基质金属蛋白酶2 （MMP-2）和MMP-9。在子宫内膜细胞和外植体中使用mPGES-1抑制剂MF63预处理后，这种效应被逆转。值得注意的是，在17β-雌二醇（10−9 M）和MF63存在的情况下，补充外源性PGE2恢复了这些生长因子的表达。综上所述，mpges -1衍生的PGE2是17β-雌二醇诱导的牛子宫内膜中FGF-2、VEGFA、MMP-2和MMP-9表达的重要介质，强调其在调节子宫内膜功能中的重要作用。

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引用次数: 0

Retraction notice to “Understanding the possible role of endocannabinoid system in obesity" [Prostaglandins Other Lipid Mediat. 152 (2021) 106520] “了解内源性大麻素系统在肥胖中的可能作用”的撤回通知[前列腺素其他脂质介质，152(2021)106520]。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-09-01 DOI: 10.1016/j.prostaglandins.2025.107027

Tapan Behl , Swati Chadha , Monika Sachdeva , Aayush Sehgal , Arun Kumar , Dhruv , Thangavel Venkatachalam , Abdul Hafeez , Lotfi Aleya , Sandeep Arora , Gaber El-Saber Batiha , Priya Nijhawan , Simona Bungau

引用次数: 0

Role of lysophosphatidic acid in the regulation of immune cells and hematological malignancies 溶血磷脂酸在免疫细胞和血液恶性肿瘤调节中的作用

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-09-01 DOI: 10.1016/j.prostaglandins.2025.107028

Vishal Kumar Gupta , Kriti Gupta , Pratishtha Sonker , Manoj Mishra , Ajay Kumar

Lysophosphatidic acid (LPA), a small bioactive glycerophospholipid, has been reported to play an indispensable role in the regulation of a wide range of cellular processes, including cell proliferation, morphology, differentiation, invasion, migration, and apoptosis. Besides, it has a diverse role in the development, differentiation, migration, and trafficking of immune cells. The role of LPA in the functioning of immune cells, such as macrophages, natural killer cells, T cells, and B cells has been poorly understood and is still a major thrust area for immunological research. Further, accumulating experimental evidence indicates the pro-tumoral action of LPA in various cancers, including hematological malignancies. Hematological malignancies or blood cancers are a group of neoplastic conditions derived from the cells of hematopoietic tissues. LPA is reported to promote the development and progression of cancers of hematological origin through altering apoptosis, invasion and migration, metabolism, and anti-tumor immune response. But still, the mechanistic pathways by which LPA supports the development and progression of hematological malignancies are not well explored. The present review aims to provide an elaborate survey on the role of LPA in the functioning of immune cells and its implication in hematological malignancies.

溶血磷脂酸（LPA）是一种小的生物活性甘油磷脂，在细胞增殖、形态、分化、侵袭、迁移和凋亡等一系列细胞过程的调控中发挥着不可或缺的作用。此外，它在免疫细胞的发育、分化、迁移和运输中具有多种作用。LPA在免疫细胞（如巨噬细胞、自然杀伤细胞、T细胞和B细胞）功能中的作用一直知之甚少，仍然是免疫学研究的主要领域。此外，越来越多的实验证据表明LPA在包括血液系统恶性肿瘤在内的各种癌症中具有促肿瘤作用。血液恶性肿瘤或血癌是一组源于造血组织细胞的肿瘤状况。据报道，LPA通过改变细胞凋亡、侵袭和迁移、代谢和抗肿瘤免疫反应，促进血液学来源的癌症的发生和进展。但是，LPA支持血液恶性肿瘤发生和发展的机制途径尚未得到很好的探索。本文就LPA在免疫细胞功能中的作用及其在血液系统恶性肿瘤中的意义作一综述。

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引用次数: 0

Corrigendum to “The association between vitamin D deficiency and childhood obesity and its impact on children’s serum calcium, alkaline phosphatase, and bone age” [Prostaglandins Other Lipid Mediat. 176 (2024) 106920] “维生素D缺乏与儿童肥胖之间的关系及其对儿童血清钙、碱性磷酸酶和骨龄的影响”[前列腺素其他脂质介质，176(2024)106920]的勘误表。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators

Pub Date : 2025-09-01 DOI: 10.1016/j.prostaglandins.2025.107025

Juanjuan Zhu , Bingbing Wang , Sanaz Asemani , Shiwei Bao , Niannian Tian

引用次数: 0