REPRODUCTION
·
2023
·
IF 3.8
Min Chen,Jia-Lu Shi,Zi-Meng Zheng,Zhi Lin,Ming-Qing Li,Jun Shao
The autophagy of trophoblasts is necessary for developing and maintaining of a healthy pregnancy. Autophagy dysfunction in trophoblast cells is linked to recurrent spontaneous abortion (RSA). However, the mechanism underlying trophoblast autophagy is unknown. In this study, we investigated the expression of autophagy-related genes in both normal and RSA villi. We also examined the production of lysophosphatidic acid (LPA) and lysophosphatidic acid receptor1 (LPAR1) in trophoblast cells during early pregnancy. We found that the activation of the LPA-LPAR1 axis triggered the autophagy of trophoblast cells and increased the expression of sodium/hydrogen exchanger 1 (NHE1). Inhibition of NHE1 suppressed the autophagy in trophoblast cells and we confirmed that NHE1 regulates LPA production in trophoblast cells. Additionally, we found decreased expression of autophagy-related genes and LPAR1 in villi from RSA patients. These observations indicate that the LPA/LPAR1-NHE1 axis regulates the autophagy of trophoblast cells during pregnancy. Insufficient autophagy and poor expression of LPAR1 in trophoblast cells may result in dysfunction of the trophoblasts and increased risk of spontaneous abortion. Overall, our research elucidated that a positive LPA/LPAR1-NHE1 axis can promote the autophagy of trophoblast cells and the abnormal axis leads to the autophagy deficiency of trophoblast cells in recurrent spontaneous abortion.
研究领域:
妇产科学
·
分子生物学
·
生殖医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2024
·
IF 4
Dingkui Xiang,Yue Ma,Jiaxu Yao,Minjie Zhao,Haijiao Li,Eric Marchioni,Li Zhou
Shiitake mushroom ( Lentinus edodes ), as a prestigious edible mushroom and one of the most famous medicinal mushrooms, is cultivated in several regions of China. In this study, the total lipids of shiitake mushroom from different origins were characterized by ultra-high-performance liquid chromatography-quadrupole-Exactive-Orbitrap MS/MS (UHPLC-QE Orbitrap/MS/MS). 20 lipid classes and 174 lipid molecular species were determined by non-targeted lipodomics analysis. The multivariate analysis showed that 19 lipids were screened as potential markers for distinguishing shiitake mushroom of different origins, for instance, phosphatidic acid (18:2/18:2) (PA 18:2/18:2) and phosphatidylglycerol (16:0/18:2) (PG 16:0/18:2). And the Partial Least Squares-Discriminant Analysis (PLS-DA) model reconstructed was used to distinguish shiitake mushroom from different regions with a success rate of 100 %. This work comprehensively provided the lipid information of shiitake mushroom and demonstrated the great potential of lipidomics for tracing the authenticity of shiitake mushrooms from different origins.
研究领域:
食品科学
·
分析化学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Biomed Research International
·
2018
·
IF 2.583
Zi-Li Yu,Bin-Fang Jiao,Zu-Bing Li
Lysophosphatidic acid (LPA), a bioactive lipid molecule, has recently emerged as physiological and pathophysiological regulator in skeletal biology. Here we evaluate the effects of LPA on bone formation in vivo in murine femoral critical defect model. Primary femoral osteoblasts were isolated and treated with osteogenic induction conditional media supplemented with 20 μM LPA or LPA analogue. Mineralized nodules were visualized by Alizarin Red S staining. Forty-five C57BL/6 mice underwent unilateral osteotomy. The femoral osteotomy gap was filled with porous scaffolds of degradable chitosan/beta-tricalcium phosphate containing PBS, LPA, or LPA analogue. 2, 5, and 10 weeks after surgery, mice were sacrificed and femurs were harvested and prepared for Micro-Computed Tomography (Micro-CT) and histological analysis. Alizarin Red S staining showed that LPA and LPA analogue significantly enhanced the mineral deposition in osteoblasts. Micro-CT 3D reconstruction images and HE staining revealed that significantly more newly formed bone in osteotomy was treated with LPA analogue when compared to control and LPA group, which was verified by histological analysis and biomechanical characterization testing. In summary, our study demonstrated that although LPA promotes mineralized matrix formation in vitro, the locally administrated LPA was not effective in promoting bone formation in vivo. And bone formation was enhanced by LPA analogue, administrated locally in vivo. LPA analogue was a potent stimulating factor for bone formation in vivo due to its excellent stability.
研究领域:
骨骼生物学
·
药理学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 103
·100891-100898
·
IF 3.289
Kun Peng,Qiqin Wang,Weijia Chen,Donghai Xia,Zhengyin Zhou,Yuqiang Wang,Zhengjin Jiang,Fuhai Wu
A novel phosphatidic acid functionalized polymeric monolithic column was prepared through the thermally initiated co-polymerization of 12-methacryloyl dodecylphosphatidic acid (MDPA) and ethylene glycol dimethacrylate (EDMA) in the presence of 1,4-butanediol and isopropanol as porogens within 100 μm I.D. capillaries. The polymerization conditions of monolithic columns were systematically optimized in order to obtain good permeability, stability and column efficiency. The reproducibility of the optimized monolithic column was also satisfactory. The physicochemical properties of the monolithic column were evaluated by use of instrumental techniques including scanning electron microscopy, Fourier transform infrared spectra, ζ-potential analysis and micro-HPLC. A series of test compounds such as small peptides, alkylphenones, etc., were employed to investigate the retention mechanism on the poly(MDPA-co-EDMA) monolithic column. The results demonstrate that both hydrophobic and cation-exchange interactions could contribute to the overall retention of analytes. Furthermore, the novel reversed-phase/cation-exchange mixed mode monolithic column was applied to the separations of small peptides, phenols, water-soluble vitamins B, and pharmaceutical compounds. The successful applications indicate the potential of the poly(MDPA-co-EDMA) monolithic column in complex sample analysis.
研究领域:
分析化学
·
色谱技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Guanghao Wu,Zhenya Liu,Changwen Mu,Da Song,Jiaxin Wang,Xiangxi Meng,Ziyuan Li,Hong Qing,Yuping Dong,Hai-Yan Xie,Dai-Wen Pang
The intrinsic features and functions of platelets and mesenchymal stem cells (MSCs) indicate their great potential in the treatment of intracerebral hemorrhage (ICH). However, neither of them can completely overcome ICH because of the stealth process and the complex pathology of ICH. Here, we fabricate hybrid cells for versatile and highly efficient ICH therapy by fusing MSCs with platelets and loading with lysophosphatidic acid-modified PbS quantum dots (LPA-QDs). The obtained LPA-QDs@FCs (FCs = fusion cells) not only inherit the capabilities of both platelets and MSCs but also exhibit clearly enhanced proliferation activated by LPA. After systemic administration, many proliferating LPA-QDs@FCs rapidly accumulate in ICH areas for responding to the vascular damage and inflammation and then efficiently prevent both the primary and secondary injuries of ICH but with no obvious side effects. Moreover, the treatment process can be tracked by near-infrared II fluorescence imaging with highly spatiotemporal resolution, providing a promising solution for ICH therapy.
研究领域:
神经科学
·
干细胞生物学
·
纳米技术
·
生物医学工程
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Lin Zeng,Yan-Qing Fu,Ying Gao,Fang Wang,Shuang Liang,Jun-Feng Yin,Marie-Laure Fauconnier,Lijing Ke,Yong-Quan Xu
In this study, widely targeted metabolomics and chemometrics were utilized to comprehensively analyse the formation of taste compounds in Longjing green tea. A total of 580 non-volatile metabolites were identified by using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and alterations in three metabolic pathways were investigated. Notably, the fixation process reduced phosphatidic acid levels, resulting in the formation of lyso-phosphatidylcholine and lyso-phosphatidylethanolamine, as well as the release of esterified polyunsaturated fatty acids. Baiye No.1 had high levels of L-glutamic acid and l -glutamine, while Longjing 43 showed elevated levels of flavones. Correlation analysis and sensory verification indicated that the specific concentration of L-leucine could decrease the umami of the tea. These findings advance our understanding of Longjing green tea quality improvement and cultivar development.
研究领域:
食品科学
·
代谢组学
·
农学
·
化学计量学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PLANT PATHOLOGY
·
2024
·Vol. 25
·期 7
·e13489
·
IF 4.8
Qiao Liu,Ruhui Long,Chaoxiang Lin,Xinping Bi,Zhibin Liang,Yi Zhen Deng
A cell death pathway, ferroptosis, occurs in conidial cells and is critical for formation and function of the infection structure, the appressorium, in the rice blast fungus Magnaporthe oryzae . In this study, we identified an orthologous lysophosphatidic acid acyltransferase (Lpaat) acting at upstream of phosphatidylethanolamines (PEs) biosynthesis and which is required for such fungal ferroptosis and pathogenicity. Two PE species, DOPE and SLPE, that depend on Lpaat function for production were sufficient for induction of lipid peroxidation and the consequent ferroptosis, thus positively regulating fungal pathogenicity. On the other hand, both DOPE and SLPE positively regulated autophagy. Loss of the LPAAT gene led to a decrease in the lipidated form of the autophagy protein Atg8, which is probably responsible for the autophagy defect of the lpaat Δ mutant. GFP-Lpaat was mostly localized on the membrane of lipid droplets (LDs) that were stained by the fluorescent dye monodansylpentane (MDH), suggesting that LDs serve as a source of lipids for membrane PE biosynthesis and probably as a membrane source of autophagosome. Overall, our results reveal novel intracellular membrane-bound organelle dynamics based on Lpaat-mediated lipid metabolism, providing a temporal and spatial link of ferroptosis and autophagy.
研究领域:
真菌学
·
植物病理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
·
2024
·
IF 7.4
Wenchao Yang,Ruijia Feng,Guiyan Peng,Zhecun Wang,Meifeng Cen,Yexiang Jing,Weiqi Feng,Ting Long,Yunchong Liu,Zilun Li,Kan Huang,Guangqi Chang
BACKGROUND:Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms.METHODS:Plasma samples from patients with arterial thrombotic events and diet-induced obese mice were collected to determine the GUDCA concentrations using mass spectrometry. Multiple in vivo murine thrombosis models and in vitro platelet functional assays were conducted to comprehensively evaluate the antithrombotic effects of GUDCA. Moreover, lipidomic analysis was performed to identify the alterations of intraplatelet lipid components following GUDCA treatment.RESULTS:Plasma GUDCA level was significantly decreased in patients with arterial thrombotic events and negatively correlated with thrombotic propensity in diet-induced obese mice. GUDCA exhibited prominent suppressing effects on platelet reactivity as evidenced by the attenuation of platelet activation, secretion, aggregation, spreading, and retraction (P<0.05). In vivo, GUDCA administration robustly alleviated thrombogenesis (P<0.05) without affecting hemostasis. Mechanistically, GUDCA inhibited DGK (diacylglycerol kinase) activity, leading to the downregulation of the phosphatidic acid–mediated signaling pathway. Conversely, phosphatidic acid supplementation was sufficient to abolish the antithrombotic effects of GUDCA. More importantly, long-term oral administration of GUDCA normalized the enhanced DGK activity, thereby remarkably alleviating the platelet hyperreactivity as well as the heightened thrombotic tendency in diet-induced obese mice (P<0.05).CONCLUSIONS:Our study implicated that GUDCA reduces platelet hyperreactivity and improves thrombotic propensity by inhibiting DGKs activity, which is a potentially effective prophylactic approach and promising therapeutic agent for arterial thrombotic events.
研究领域:
心脏病学
·
药理学
·
血栓
·
脂质代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL CYCLE
·
2022
·
IF 5.173
Feng Zhang,Peng Liu,Zhaopeng He,like Zhang,Xinqi He,Feng Liu,Jinsheng Qi
Crocin (CRO) is feasible in alleviating atherosclerosis (AS), the mechanism of which was therefore explored in the study. High-fat diet (HFD)-induced apolipoprotein E-deficient (ApoE−/−) mice and lysophosphatidic acid (LPA)-treated macrophages received CRO treatment. Treated macrophage viability was determined via MTT assay. In both murine and macrophage, the lipid level and total Cholesterol/Cholesteryl l Ester (TC/CE) levels were quantified by oil-red-O staining and ELISA, respectively. Lipid droplet, aortic plaque formation and collagen deposition were detected via Oil-red-O staining, hematoxylin–eosin staining and Masson staining, respectively. Liver X Receptor-α (LXR-α), Peroxisome Proliferator-Activated Receptor γ (PPARγ), CD68, PCSK9, CD36, ATP Binding Cassette Subfamily A Member 1 (ABCA1), phosphorylated (p)-AKT, and AKT expressions were detected via Western blot, the former three also being detected using Immunohistochemistry and the first being measured by qRT-PCR. CRO decreased HFD-induced weight gain, ameliorated the abnormal serum lipid levels of HFD-treated mice, and inhibited aortic plaque formation and lipid deposition, and increased collagen fibers, with upregulated high-density lipoprotein-cholesterol (HDL-C) and downregulated TC and low-density lipoprotein-cholesterol (LDL-C). CRO alleviated the HFD-induced upregulations of CD68, PCSK9 and CD36 as well as downregulations of PPARγ/LXR-α, ABCA1 and AKT phosphorylation. In LPA-treated macrophages, CRO alone exerted no effect on the viability yet inhibited the lipid droplets formation and downregulated TC/CE levels. Silent LXR-α reversed the effect of CRO on the lipid droplets formation and levels of lipid metabolism-related factors. CRO ameliorated AS by inhibiting foam cells formation and promoting reverse cholesterol transport via PPARγ/LXR-α.
研究领域:
心脏病学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·
IF 5.228
Zhe Chen,Qing Luo,Chuanchuan Lin,Dongdong Kuang,Guanbin Song
Microgravity induces observed bone loss in space flight, and reduced osteogenesis of bone mesenchymal stem cells (BMSCs) partly contributes to this phenomenon. Abnormal regulation or functioning of the actin cytoskeleton induced by microgravity may cause the inhibited osteogenesis of BMSCs, but the underlying mechanism remains obscure. In this study, we demonstrated that actin cytoskeletal changes regulate nuclear aggregation of the transcriptional coactivator with PDZ-binding motif (TAZ), which is indispensable for osteogenesis of bone mesenchymal stem cells (BMSCs). Moreover, we utilized a clinostat to model simulated microgravity (SMG) and demonstrated that SMG obviously depolymerized F-actin and hindered TAZ nuclear translocation. Interestingly, stabilizing the actin cytoskeleton induced by Jasplakinolide (Jasp) significantly rescued TAZ nuclear translocation and recovered the osteogenic differentiation of BMSCs in SMG, independently of large tumor suppressor 1(LATS1, an upstream kinase of TAZ). Furthermore, lysophosphatidic acid (LPA) also significantly recovered the osteogenic differentiation of BMSCs in SMG through the F-actin-TAZ pathway. Taken together, we propose that the depolymerized actin cytoskeleton inhibits osteogenic differentiation of BMSCs through impeding nuclear aggregation of TAZ, which provides a novel connection between F-actin cytoskeleton and osteogenesis of BMSCs and has important implications in bone loss caused by microgravity.
研究领域:
生物医学工程
·
细胞生物学
·
干细胞研究
·
空间生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Yongkang Lai,Tinglin Zhang,Xiaojing Yin,Chunping Zhu,Yiqi Du,Zhaoshen Li,Jie Gao
Helicobacter pylori ( H. pylori) infection remains the leading cause of gastric adenocarcinoma, and its eradication primarily relies on the prolonged and intensive use of two antibiotics. However, antibiotic resistance has become a compelling health issue, leading to H. pylori eradication treatment failure worldwide. Additionally, the powerlessness of antibiotics against biofilms, as well as intracellular H. pylori and the long-term damage of antibiotics to the intestinal microbiota, have also created an urgent demand for antibiotic-free approaches. Herein, we describe an antibiotic-free, multifunctional copper-organic framework (HKUST-1) platform encased in a lipid layer comprising phosphatidic acid (PA), rhamnolipid (RHL), and cholesterol (CHOL), enveloped in chitosan (CS), and loaded in an ascorbyl palmitate (AP) hydrogel: AP@CS@Lip@HKUST-1. This platform targets inflammatory sites where H. pylori aggregates through electrostatic attraction. Then, hydrolysis by matrix metalloproteinases (MMPs) releases CS-encased nanoparticles, disrupting bacterial urease activity and membrane integrity. Additionally, RHL disperses biofilms, while PA promotes lysosomal acidification and activates host autophagy, enabling clearance of intracellular H. pylori . Furthermore, AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu 2+ release while preserving the intestinal microbiota. Collectively, this platform presents an advanced therapeutic strategy for eradicating persistent H. pylori infection without inducing drug resistance.
研究领域:
胃肠病学
·
药学
·
微生物学
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2023
·Vol. 22
·期 1
·1-14
·
IF 4.5
Tan Lunbo,Ouyang Zijun,Chen Zhilong,Sun Fen,Guo Haichun,Wang Feng,Mulder Monique,Sun Yuan,Lu Xifeng,Zhang Jian V.,Danser A. H. Jan,Verdonk Koen,Fan Xiujun,Yang Qing
Background The adipokine chemerin regulates adipogenesis and the metabolic function of both adipocytes and liver. Chemerin is elevated in preeclamptic women, and overexpression of chemerin in placental trophoblasts induces preeclampsia-like symptoms in mice. Preeclampsia is known to be accompanied by dyslipidemia, albeit via unknown mechanisms. Here, we hypothesized that chemerin might be a contributor to dyslipidemia. Methods Serum lipid fractions as well as lipid-related genes and proteins were determined in pregnant mice with chemerin overexpression in placental trophoblasts and chemerin-overexpressing human trophoblasts. In addition, a phospholipidomics analysis was performed in chemerin-overexpressing trophoblasts. Results Overexpression of chemerin in trophoblasts increased the circulating and placental levels of cholesterol rather than triglycerides. It also increased the serum levels of lysophosphatidic acid, high-density lipoprotein cholesterol (HDL-C), and and low-density lipoprotein cholesterol (LDL-C), and induced placental lipid accumulation. Mechanistically, chemerin upregulated the levels of peroxisome proliferator-activated receptor g, fatty acid-binding protein 4, adiponectin, sterol regulatory element-binding protein 1 and 2, and the ratio of phosphorylated extracellular signal-regulated protein kinase (ERK)1/2 / total ERK1/2 in the placenta of mice and human trophoblasts. Furthermore, chemerin overexpression in human trophoblasts increased the production of lysophospholipids and phospholipids, particularly lysophosphatidylethanolamine. Conclusions Overexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.
研究领域:
妇产科学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子