Frontiers in Pharmacology
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2025
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IF 4.8
Yancen Li,Chengyu Wan,Fan Li,Guang Xin,Tao Wang,Qilong Zhou,Tingyu Wen,Shiyi Li,Xiaoting Chen,Wen Huang
Background: Isatidis Folium, a botanical drug widely used in traditional medicine, is known for its anti-inflammatory properties, including heat-clearing, detoxifying, and blood-cooling effects. Although its potential in sepsis treatment has been suggested, the bioactive metabolites and underlying mechanisms remain poorly understood.Methods: Network pharmacology and molecular docking were employed to identify the therapeutic effects and mechanisms of Indirubin, the major bioactive metabolite of Isatidis Folium, in sepsis treatment. In vivo, a cecal ligation and puncture (CLP)-induced mouse sepsis model was used to evaluate the protective effects of Indirubin through histopathological analysis, ELISA, and biochemical assays. In vitro, RAW264.7 cells were stimulated with LPS and treated with varying concentrations of Indirubin. The anti-inflammatory effects of Indirubin were assessed using ELISA, apoptosis assays, and Western blotting.Results: Network pharmacology analysis identified Indirubin as the major bioactive metabolite of Isatidis Folium and EGFR and SRC as its key molecular targets. Experimental validation demonstrated that Indirubin significantly improved survival rates, alleviated tissue injury, and suppressed inflammatory responses in sepsis models. Mechanistically, Indirubin inhibited LPS-induced activation of the EGFR/SRC/PI3K and NF-κB/MAPK pathways in macrophages, significantly reducing cell death and inflammation in RAW264.7 cells.Conclusion: Indirubin, the primary bioactive metabolite of Isatidis Folium, exerts protective effects against sepsis by targeting the EGFR/SRC/PI3K and NF-κB/MAPK signaling pathways in macrophages. These findings provide a mechanistic basis for the development of Indirubin as a multi-target therapeutic agent for sepsis treatment.
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2015
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IF 4.383
Zhenzhen Liu,Haijun Gong,Rui Zeng,Xuan Liang,Li-Ming Zhang,Liqun Yang,Yuqing Lan
A hyperbranched cationic polysaccharide derivative-mediated small interfering (si)RNA interference strategy was proposed to inhibit nuclear transcription factor-kappa B (NF-κB) activation in human retinal pigment epithelial (hRPE) cells for the gene therapy of diabetic retinopathy. Two hyperbranched cationic polysaccharide derivatives containing the same amount of cationic residues, but with different branching structures and molecular weights, including 3-(dimethylamino)-1-propylamine-conjugated glycogen (DMAPA-Glyp) and amylopectin (DMAPA-Amp) derivatives, were developed for the efficient delivery of NF-κB siRNA into hRPE cells. The DMAPA-Glyp derivative showed lower toxicity against hRPE cells. Furthermore, the DMAPA-Glyp derivative more readily condensed siRNA and then formed the nanoparticles attributed to its higher branching architecture when compared to the DMAPA-Amp derivative. Both DMAPA-Glyp/siRNA and DMAPA-Amp/siRNA nanoparticles were able to protect siRNA from degradation by nuclease in 25% fetal bovine serum. The particle sizes of the DMAPA-Glyp/siRNA nanoparticles (70–120 nm) were smaller than those of the DMAPA-Amp/siRNA nanoparticles (130–180 nm) due to the higher branching architecture and lower molecular weight of the DMAPA-Glyp derivative. In addition, the zeta potentials of the DMAPA-Glyp/siRNA nanoparticles were higher than those of the DMAPA-Glyp/siRNA nanoparticles. As a result, siRNA was much more efficiently transferred into hRPE cells using the DMAPA-Glyp/siRNA nanoparticles rather than the DMAPA-Amp/siRNA nanoparticles. This led to significantly high levels of suppression on the expression levels of NF-κB p65 messenger RNA and protein in the cells transfected with DMAPA-Glyp/siRNA nanoparticles. This work provides a potential approach to promote hyperbranched polysaccharide derivatives as nonviral siRNA vectors for the inhibition of NF-κB activation in hRPE cells.
研究领域:
药理学
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分子生物学
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眼科学
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基因治疗
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产品关联
DOI
PubMed
高影响因子
ELECTROCHIMICA ACTA
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2023
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IF 6.6
Sirong Li,Yipeng Zhang,Xin Yu,Zhenlong Wang,Guofei Zhang,Zhengyi Zhao,Zhiyong Yan,Xuechun Xiao
An environmentally friendly method of producing hydrogen is electrocatalytic water splitting, but the high theoretical potential of the anode's OER (1.23 V vs. RHE) restricts the efficiency of hydrogen production . Therefore, using the urea oxidation reaction (UOR, theoretical potential of 0.37 V vs. RHE) in place of the OER can significantly increase the efficiency of hydrogen production. Here, we grow the hydroxide layer of Ni-Co-Fe directly on NF by one-step electrodeposition and obtain the best catalyst by regulating the elemental ratio of Co and Fe. Through tests, it is found that NiCoFe(OH) x /NF(Co: Fe=3: 1) exhibits the best electrocatalytic performance, and the required potential is only 1.24 and 1.30 V when the current density reaches 10 and 50 mA cm −2 in the UOR process, which is 170 and 140 mV lower than the OER overpotential under the same conditions, showing a more advantageous anodic catalytic effect. At the same time, integral water decomposition in an electrolyte of 1 M KOH adds with 0.5 M urea also shows more favorable catalytic activity and stability. The NiCoFe(OH) x /NF(Co: Fe=3: 1) plays an important role in improving the efficiency of hydrogen production by water splitting through simple electrodeposition, and has sustainable development prospects.
研究领域:
材料科学
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电化学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
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2023
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IF 7.2
Yali Yao,Jinmei He,Xuedan Zhu,Leihuan Mu,Jiehui Li,Kanshe Li,Mengnan Qu
Rationally designing cost-efficient, high-activity and durable electrocatalysts are used for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is sense to solve the energy crisis and conversion. Herein, the heterostructure superwetting Co–MoS 2 /Ni 3 S 2 -GO/NF electrode is successfully fabricated by a typical hydrothermal reaction and it's electrocatalytic performance is also systematically studied. Thanks to the establishment of Co doped MoS 2 /Ni 3 S 2 heterojunction , the improvement conductivity by the addition of graphene oxide (GO), and the superhydrophilicity and superaerophobicity of microstructure, the electrode shows excellent catalytic characteristics and only need an overpotential of 123 mV for OER and 161 mV for HER to reach 10 mA cm −2 and can work steadily for 15 h in alkaline solution. Remarkebly, the superwetting heterojunction electrode demonstrated excellent overall water decomposition ability when used as bifunctional electrocatalyst in 1.0 M KOH and only 1.47 V is required to achieve 10 mA cm −2 . Density functional theory (DFT) calculations show the constructed heterogeneous interface and Co doping are conducive to optimizing the chemisorption energy of hydrogen-containing intermediates. This work provides a new way of thinking that collaborative optimization of electrode structure and surface wettability regulation to increase the active area of reaction and accelerate the bubble release toward high-performance OER and HER electrodes .
研究领域:
材料科学
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电化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Yan Zhou,Tian Wen,Shan Yang,Binru Meng,Jing Wei,Jing Zhang,Lun Wang,Xiaofei Shen
Ethnopharmacological relevance Cichorium intybus is a traditional medicinal herb for hepatitis treatment in China and Europe. Sesquiterpene lactones are the main active ingredients in C. intybus . However, their structure-activity relationship (SAR) and molecular mechanisms of anti-inflammatory and hepatoprotective effects require further elucidation. Aim of the study To identify new sesquiterpene lactones from C. intybus , and further evaluate their anti-inflammatory effects, SAR, and mechanisms of anti-inflammatory and hepatoprotective properties. Methods Identification of sesquiterpene lactones from C. intybus using chromatographic fractionation, NMR, and mass spectrometry. The repression of inflammation was evaluated in RAW264.7 macrophages incubated with LPS. Western blotting was employed to investigate the anti-inflammatory mechanisms. The hepatoprotective effect was measured in LPS/D-galactosamine (D-GalN)-induced acute hepatitis in mice. Results We identified 3 new sesquiterpene lactones and 15 known analogues from C. intybus . SAR analysis showed that the α-methylene-γ-lactone moiety was essential for their anti-inflammatory properties. Furthermore, 8-deoxylactucin was identified as the most potent anti-inflammatory component in LPS-induced RAW264.7 macrophages by reduction of nitric oxide production via inhibiting iNOS expression, and suppression of IL-1β, IL-6, and TNF-α expression. Mechanistically, 8-deoxylactucin not only blocked LPS-induced IKKα/β phosphorylation, IκBα phosphorylation and degradation, and NF-κB nuclear accumulation, but also enhanced NRF2 expression and nuclear translocation, HO-1 and NQO1 expression, and reduced ROS generation in vitro . In vivo , 8-deoxylactucin mitigated LPS/D-GalN-induced acute hepatitis, which manifested as reduction in inflammatory infiltration, live injury, serum levels of AST and ALT, and production of pro-inflammatory cytokines and 4-hydroxynonenal. Conclusion 8-Deoxylactucin, the sesquiterpene lactone isolated from C. intybus , exerted anti-inflammatory and hepatoprotective effects by blocking NF-κB activation and enhancing NRF2 activation.
研究领域:
药理学
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植物化学
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2024
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IF 2.5
Jinyun Long,Xiukuan Li,Chunyan Yao,Xiaoling Liu,Na Li,Yumeng Zhou,Dawei Li,Shengquan Su,Liangmei Wang,Hao Liu,Ying Xiang,Long Yi,Yao Tan,Peng Luo,Tongjian Cai
Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 μg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.
研究领域:
神经科学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PATHOLOGY
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2025
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IF 5.2
Fang Liu,Qingchun Liang,Li Li,Yuan Gong,Mingxi Li,Liyun Feng,An Chen,Yuanzhi Ye,Zirong Lan,Yining Li,Jing-Song Ou,Lihe Lu,Jianyun Yan
Vascular calcification is an important risk factor related to all-cause mortality of cardiovascular events in patients with chronic kidney disease (CKD). Vascular extracellular matrix (ECM) proteins have been demonstrated to regulate vascular calcification. ECM protein thrombospondin 1 (THBS1/TSP-1) plays a critical role in the regulation of vascular diseases. However, whether THBS1 is involved in vascular calcification in CKD patients remains unclear. In this study, RNA sequencing datasets from the Gene Expression Omnibus (GEO) database GSE146638 showed that THBS1 was upregulated in the aortas of CKD rats. Enzyme-linked immunosorbent assay (elisa) revealed that serum THBS1 levels were increased in CKD patients with thoracic calcification. Western blotting and immunofluorescence analysis showed that THBS1 expression was increased in calcified vascular smooth muscle cells (VSMCs) and arteries. THBS1 knockdown exacerbated rat VSMC calcification induced by high phosphorus and calcium, as shown by Alizarin red staining and calcium content assays. Conversely, THBS1 overexpression attenuated VSMC calcification and abdominal aortic calcification in rats with CKD. Moreover, addition of recombinant THBS1 protein inhibited calcification of VSMC S and human arterial rings. Smooth muscle cell-specific knockout of THBS1 mice treated with vitamin D3 displayed aggravated aortic calcification. Mechanistically, the protein–protein interaction database STRING ( http://string-db.org/ ) analysis and coimmunoprecipitation assays revealed THBS1 bound to integrin β3. Reduction of integrin β3 levels abrogated the protective effect of THBS1 on vascular calcification. RNA-seq analysis revealed that THBS1 overexpression modulated the nuclear factor-kappa B (NF-κB) signaling pathway. Of note, the inhibitory effect of THBS1 overexpression on the NF-κB signal was abolished by knockdown of integrin β3. In conclusion, THBS1 interacts with integrin β3 to inhibit vascular calcification through suppression of NF-κB signal, suggesting a promising therapeutic target for vascular calcification in CKD. © 2025 The Pathological Society of Great Britain and Ireland.
研究领域:
医学
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分子生物学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2024
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IF 3.8
Xinzhang Chen,Xu Lin
Trimethyl tin (TMT) is a good stabilizer for plastic products but is also a toxic environmental pollutant. Selenium has good antioxidant and anti-inflammatory properties and has been widely used in the poultry industry. However, it has not been reported whether selenium enrichment can antagonize TMT-induced viral hepatitis in poultry. To fill this gap, AA broiler models exposed to TMT for 42 d were established and fed a Se-enriched diet at the same time. H&E staining showed that selenium could significantly alleviate TMT-induced liver inflammation. Further analysis of the underlying mechanism revealed that TMT induced nitrosation stress (RNS), increased NO content and iNOS expression, which in turn activated the NF-κB/NLRP3 pathway and induced pyroptosis. However, selenium enrichment can reverse this situation, that is, reduce the occurrence of RNS, reduce the degree of pyroptosis, and thus alleviate the occurrence of inflammation. In our study, we demonstrated for the first time that TMT could induce hepatotoxicity other than neurotoxicity in poultry and that selenium could antagonize TMT-induced hepatotoxic hepatitis in chickens through the RNS/NF-κB/NLRP3 pathway.
研究领域:
毒理学
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兽医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
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2023
·Vol. 25
·期 6
·1-12
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IF 2.9
Boya Deng,Ailin Li,Ying Zhu,Yingying Zhou,Jing Fei,Yuan Miao
Cervical cancer (CC) is the most common human papillomavirus‑related disease. Continuous activation of the NF‑κB signaling pathway has been observed in CC. SHC binding and spindle associated 1 (SHCBP1) contributes to tumorigenesis and activation of the NF‑κB pathway in multiple cancer types, while its function in CC remains unclear. In the present study, three Gene Expression Omnibus datasets were used to identify differentially expressed genes (DEGs) in CC. Loss‑ and gain‑of‑function experiments were performed using stable SHCBP1‑silenced and SHCBP1‑overexpressing CC cells. To further explore the molecular mechanism of SHCBP1 in CC, small interfering RNA targeting eukaryotic translation initiation factor 5A (EIF5A) was transfected into stable SHCBP1‑overexpressing CC cells. The results demonstrated that SHCBP1 was an upregulated DEG in CC tissues compared with healthy control cervical tissues. Functional experiments revealed the pro‑proliferative and pro‑stemness role of SHCBP1 in CC cells (CaSki and SiHa cells), in vitro. Furthermore, the NF‑κB signaling pathway in CC cells was activated by SHCBP1. Increases in cell proliferation, stemness and activation of NF‑κB, induced by SHCBP1 overexpression in CC cells, were reversed by EIF5A knockdown. Taken together, the results indicated that SHCBP1 serves an important role in regulation of CC cell proliferation, self‑renewal and activation of NF‑κB via EIF5A. The present study demonstrated a potential molecular mechanism underlying the progression of CC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Oncotarget
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2016
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IF 5.008
Yuan Qin,Dong Zhao,Hong-gang Zhou,Xing-hui Wang,Wei-long Zhong,Shuang Chen,Wen-guang Gu,Wei Wang,Chun-hong Zhang,Yan-rong Liu,Hui-juan Liu,Qiang Zhang,Yuan-qiang Guo,Tao Sun,Cheng Yang
Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo . Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-κB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2017
·Vol. 14
·期 5
·4174-4180
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IF 1.261
Chuan‑Feng Huang,Wei‑Na Wang,Cheng‑Cao Sun,Yu‑Qing Wang,Ling Li,Yin Li,De‑Jia Li
The present study investigated the role of echinocystic acid (EA) on the expression of nuclear factor (NF)‑κB and cytochrome P450 1A1 (CYP1A1), and aortic morphology, in a rat model of hyperhomocysteinemia (Hhcy). A total of 50 Sprague Dawley rats were randomly divided into five groups as follows: Normal control (NC), model control (MC), vitamin control (VC; folic acid 1 mg/kg + vitamin B2 2 mg/kg + vitamin B12 10u g/kg), EA1 (20 mg/kg EA) and EA2 (40 mg/kg EA). Plasma homocysteine (Hcy) levels were determined via high performance liquid chromatography, and the morphology of the aorta was investigated using hematoxylin and eosin staining. Furthermore, aortic mRNA and protein levels of NF‑κB and CYP1A1 were measured using reverse transcription‑quantitative polymerase chain reaction analysis and western blotting, respectively. Plasma Hcy levels, and aortic mRNA and protein levels of NF‑κB and CYP1A1, were significantly lower in the EA‑treated group compared with the MC group (all P<0.05). However, the aortic morphology remained normal, including the endothelial cells of the inner layer, and smooth muscle cells of the media layer and adventitia. In conclusion, the results of the present study indicate that EA has a protective role on vascular endothelial cells in Hhcy through decreasing plasma Hcy, and thus NF‑κB and CYP1A1 expression.
研究领域:
药理学
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分子生物学
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心血管疾病
✓ 已验证
DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2023
·Vol. 11
·期 5
·e879
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IF 3.2
Xiuping Zhang,Yuanjing Hu,Zhiping Zhang,Xueluo Zhang,Lixia Liang,Xiangrong Cui,Yuanxia Wu,Fen Hu,Xueqing Wu
Introduction Approximately 50% of cases with recurrent spontaneous abortion (RSA) have unexplained etiology. Aberrant expression of transmembrane and ubiquitin-like domain containing 1 (TMUB1) is closely related to a series of diseases, including RSA. However, the function and underlying mechanism of TMUB1 in the occurrence of RSA has not been described. Methods TMUB1 expression was detected in the placental villous tissues of 30 women with normal miscarriages and 12 women with RSA. The pregnant mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce abortion. Human chorionic trophoblast cells were treated with LPS. Pathological analysis of placental tissues was performed by hematoxylin and eosin staining. Results TMUB1 was highly expressed in the placental villous tissues of RSA patients compared to the patients who underwent induced abortions. After LPS administration, the mice exhibited high embryo absorption and pathological alterations, as well as presented an increase in inflammation and apoptosis (the etiology of RSA induction) in placental tissues. Moreover, the upregulated expression of TMUB1 was also found in placental tissues of LPS-induced mice, and further investigation showed that TMUB1 deficiency blocked embryo loss as well as inhibited apoptotic rate and inflammation after LPS activation. Furthermore, we found that the loss of TMUB1 suppressed the phosphorylation of IkappaB kinase (IKK) α/β and attenuated cytoplasmic-nuclear translocation of nuclear factor-κB (NF-κB) p65 in LPS-induced cells. Conclusion Our results indicate that TMUB1 may involve in the modulation of apoptosis and NF-κB pathway-mediated inflammation in RSA. Therefore, TMUB1 may develop as a potential biomarker for RSA treatment.
研究领域:
妇产科学
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分子生物学
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免疫学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
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