查找使用阿拉丁产品的科研文献

PREX1 depletion ameliorates high-fat diet-induced non-alcoholic fatty liver disease in mice and mitigates palmitic acid-induced hepatocellular injury via suppressing the NF-κB signaling pathway

Zeyu Li,Kanglin Wu,Yi Zou,Wei Gong,Peng Wang,Hong Wang

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide. Oxidative stress has been considered a key factor in the pathogenesis of NAFLD. Phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 (PREX1), a guanine nucleotide exchange factor for Rac, has been associated with inflammation and oxidative stress. This study aimed to investigate the biological function of PREX1 in the progression of NAFLD. Male C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD in vivo. Adeno-associated virus type 8-mediated liver-specific PREX1 depletion was employed to investigate the role of PREX1 in the progression of high-fat diet-induced NAFLD. Murine hepatocyte cell line AML-12 was stimulated with palmitic acid for 24 h to induce steatosis in vitro. PREX1 depletion was carried out by transfection with PREX1 small interfering RNA . Results showed that PREX1 depletion exerted protective effects against lipid accumulation, oxidative stress and inflammation and inhibited activation of the nuclear factor-κB (NF-κB) signaling pathway in vivo and in vitro. Subsequently, NF-κB inhibitor BAY11–7082 was applied to investigate the role of the NF-κB signaling pathway in the protective effect of PREX1 inhibition against NAFLD. We confirmed that PREX1 inhibition mitigated palmitic acid-induced hepatocellular inflammation mainly via the NF-κB signaling pathway and lipid accumulation and oxidative stress at least partly via the NF-κB signaling pathway. This study highlights the biological function of PREX1 in the pathogenesis of NAFLD.

Grape Seed Procyanidin Reversal of P-glycoprotein Associated Multi-Drug Resistance via Down-regulation of NF-κB and MAPK/ERK Mediated YB-1 Activity in A2780/T Cells

Bo-xin Zhao,Ya-bin Sun,Sheng-qi Wang,Lian Duan,Qi-lu Huo,Fei Ren,Guo-feng Li

The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.

Overcoming dual dehydrogenation barriers in the oxidation of 1-methoxy-2-propanol on the electronically modulated Mn–Ni(OH)2/NF electrode for efficient production 1-methoxy-2-propanone

Xingyu Han,FangFang Liu,Hanxiao Wang,Yangjing Liu,Shuhui Huo,Min Wang,Jianwei Ren,Xuyun Wang,Hongbing Song,Jian Liu,Rongfang Wang

Ni(OH) 2 /NF demonstrates strong electrocatalytic performance in the oxidation of 1-methoxy-2-propanol (MOP) to 1-methoxy-2-propanone (MOA). However, its catalytic efficiency is restricted by two sluggish dehydrogenation stages: the oxidation of Ni 2 + –OH to generate the active Ni 3+ –O intermediate, and the abstraction of the α-hydrogen from the MOP molecule. To address these limitations, the present study introduces a strategy centered on tuning the electronic structure. By incorporating manganese (Mn) into the coordination structure of Ni(OH) 2 /NF nanosheets in a controlled manner, both reaction steps are effectively enhanced through synergistic effects. X-ray photoelectron spectroscopy (XPS) and synchrotron-based X-ray absorption fine structure (XAFS) analyses reveal that Mn incorporation modifies the local electronic environment of Ni through electronic interactions. This adjustment decreases the d -orbital electron density of Ni, thereby facilitating the oxidation of Ni 2+ to the catalytically active Ni 3+ species during MOP conversion. Electrochemical measurements combined with density functional theory (DFT) calculations indicate that Mn incorporation markedly enhances the adsorption of MOP molecules on the catalyst surface, which thereby promotes more efficient reaction kinetics. This synergistic regulation effectively lowers the energy barrier associated with the dual dehydrogenation steps, resulting in markedly improved catalytic performance of Mn–Ni(OH) 2 /NF for MOP oxidation, with the product Faradaic efficiency reaching around 90 %.

Paeonia delavayi seed oil rich in oleic acid and linolenic acid alleviates UVB-induced inflammation and oxidative stress in keratinocytes through inhibition of PI3K/Akt and NF-κB pathways

Rencong Wang,Peng Xu,Yindi Zhang,Xiaoli Jin,Ziyan Zhao,Liping Qu,Feifei Wang

Excessive exposure to UVB can induce inflammatory responses and oxidative stress, leading to skin damage. Peony seed oil is rich in unsaturated fatty acids and has been reported to possess anti-inflammatory and antioxidant properties. This study investigated the protective effects and underlying mechanisms of Paeonia delavayi seed oil (PDSO) against UVB-induced damage in human keratinocytes. PDSO at 30–120 μg/mL attenuated UVB-induced inflammation by reducing the mRNA expression of TNF , IL6 , CXCL8 , and PTGS2 and suppressing the secretion of IL-6 and IL-8. PDSO also inhibited UVB-induced activation of NF-κB signaling. Regarding oxidative stress, 120 μg/mL PDSO reduced intracellular ROS production, decreased MDA levels by approximately 29.4%, and increased SOD activity by approximately 122.0% compared with the UVB group. PDSO also increased the mRNA expression of antioxidant-related genes, including NFE2L2, HMOX1, SOD1, CAT, GCLC, and GCLM . In addition, PDSO alleviated the UVB-induced reduction in keratinocyte viability and attenuated photoaging-related changes. Transcriptomic analysis identified PI3K/Akt signaling as a candidate pathway associated with PDSO treatment, and western blotting further showed that PDSO inhibited UVB-induced PI3K/Akt signaling. Pharmacological intervention with the PI3K activator 740Y P partially reversed the anti-inflammatory effects of PDSO, whereas LY294002 exerted anti-inflammatory effects and further enhanced those of PDSO. Moreover, oleic acid and linolenic acid alleviated UVB-induced inflammation and oxidative stress. Collectively, PDSO protects keratinocytes against UVB-induced damage, with PI3K/Akt and NF-κB signaling contributing to its protective effects. Download: Download high-res image (117KB) Download: Download full-size image

Edaravone dexborneol ameliorates cognitive impairment by regulating the NF-κB pathway through AHR and promoting microglial polarization towards the M2 phenotype in mice with bilateral carotid artery stenosis (BCAS)

Lei Li,Guojun He,Mingyu Shi,Juehua Zhu,Yongqing Cheng,Yang Chen,Jin Chen,Qun Xue

Cerebral small vessel disease (CSVD) is one of the most important causes of stroke and vascular dementia , so exploring effective treatment modalities for CSVD is warranted. This study aimed to explore the anti-inflammatory effects of Edaravone dexborneol (C.EDA) in a CSVD model. Mice with CSVD showed distinct cognitive decline, as assessed by the Morris water maze (MWM). Pathological staining verified leakage across the blood‒brain barrier (BBB), microglial proliferation, neuronal loss and demyelination . Western blot analysis demonstrated that M1 microglia dominated prophase and released proinflammatory molecules; the aryl hydrocarbon receptor (AHR) was found to participate in modulating nuclear factor-kappa B (NF-κB) signalling activation through tumour necrosis factor receptor-associated factor-6 (TRAF6). C.EDA treatment resulted in the polarization of microglia from the M1 to the M2 phenotype. Mice sequentially treated with C.EDA exhibited a significant improvement in cognitive function; expression of the anti-inflammatory cytokines and modulatory proteins AHR and TRAF6 was upregulated, while the levels of pNF-κBp65 and pIΚBα were downregulated. C.EDA promoted microglial activation towards the M2 phenotype by upregulating AHR expression, which prevented TRAF6 ubiquitination , promoted NF-κB RelA/p65 protein degradation and inhibited subsequent NF-κB phosphorylation. Mechanistically, the anti-inflammatory effect of C.EDA alleviated neuronal loss and myelin damage, while at the functional level, C.EDA improved cognitive function and thus showed good application prospects.

Isoferulic Acid Inhibits Proliferation and Migration of Pancreatic Cancer Cells, and Promotes the Apoptosis of Pancreatic Cancer Cells in a Mitochondria-Dependent Manner Through Inhibiting NF-κB Signalling Pathway

Suqin Sun,Rong Fan,Li Chang,Lei Gao,Chunting Liu,Dongying Liu,Shiyu Niu

Isoferulic acid (IA), a derivative of cinnamic acid, is derived from Danshen and exhibits anticancer properties by disrupting cancer cell activities. However, its role in pancreatic cancer, the “king of cancer”, was unknown. In this study, pancreatic cancer cells were subjected to treatment with IA (6.25, 12.5, 25 μM), and nude mice injected with pancreatic cancer cells were received IA at doses of 7.5 mg/kg/day or 30 mg/kg/day by oral administration. CCK8, Annexin V-FITC/propidium iodide (PI) double staining and TUNEL assay were conducted to evaluate the cell viability and apoptosis. Hoechst staining and comet assay was employed to measure DNA damage. Mitochondrial membrane potential (MMP) analysis was carried out to explain the mitochondrial damage. EdU and wound healing assay were performed for cell proliferation and migration detection. Immunofluorescence and western blot were used to explore the mechanism. We found that IA reduced cell viability and induced apoptosis, as evidenced by an increase in Annexin V-FITC + PI − and Annexin V-FITC + PI + cell populations, brighter TUNEL and Hoechst staining, and more percentage of tail DNA. Furthermore, IA decreased MMP and changed levels of apoptosis-related proteins. The cell proliferation and migration were inhibited by IA treatment. Mechanically, IA downregulated the phosphorylation of IĸBα and inhibited p65 nuclear translocation, consequently suppressing NF-κB pathway. In general, IA suppressed the cell proliferation and migration, and caused apoptosis of pancreatic cancer cells in a mitochondria-dependent manner through blocking NF-κB signalling pathway, indicating that IA may be a potential therapeutic strategy for pancreatic cancer.

Nano FeNi-OH/Co(OH)2/NF p-n heterojunction for efficient oxygen evolution reaction and electrocatalytic urea oxidation: Built-In electric field regulated charge distribution and mechanism exploration

Yulan Song,Cuilan Tang,Tao Wang,Yansong Liu,Xiaoshan He,Chunping Xie,Guo Chen,Chengfu Deng,Zhibing He,Jinglin Huang

Constructing electronic structures with abundant surface/interface structures and effective regulation of catalytic active centers is an effective strategy to improve electrocatalytic performance, but designing efficient bifunctional non-noble metal oxygen evolution reaction (OER) and urea oxidation reaction (UOR) electrocatalysts remains challenging. Studies have shown that p-n heterojunctions can effectively regulate the electronic structure of catalytic active sites while having abundant surface/interface structure, which plays an important role in improving the native catalytic activity. Herein, FeNi-OH/Co(OH) 2 /NF p-n heterojunction structure was constructed by a simple electrochemical deposition method, and the effects of content, deposition time, and number of cycles on catalytic performance were investigated. The results show that Fe(0.02 M)Ni(0.07 M)–OH(100 s)/Co(OH) 2 (5)/NF composite material has the best OER and UOR catalytic performance. For OER, the electrocatalyst only requires an overpotential of 271 mV to obtain a current density of 50 mA cm −2 , and an applied voltage of 1.56 V to obtain a total water decomposition of 10 mA cm −2 (FeNi-OH/Co(OH) 2 /NF||Pt). For UOR, a voltage of only 1.314 V ( vs. RHE) is required to achieve a current density of 10 mA cm −2 , and an applied voltage of 1.44 V can achieve a current density of 10 mA cm −2 . Experimental, in situ measurements and theoretical results indicate that the improvement in catalytic activity is mainly due to the potential difference between FeNi-OH and Co(OH) 2 , which induces self-driven charge transfer at the interface, promoting the adsorption of reactant molecules, optimizing reaction barriers, accelerating chemical bond cleavage, and thus promoting catalytic reactions.

Atraric acid alleviates high-fat diet-induced renal injury, lipid accumulation, and fibrosis in mice by regulating oxidative stress and inflammation through AMPK-dependent Nrf2 and NF-κB signaling pathways

Yannan Xiang,Tianyue Guan,Jun Wang,Shasha Zhang,Yusa Li,Jing Xia,Panpan Zhao,Lei Wang

This study explores the protective effects of Atraric Acid (AA) against chronic kidney disease (CKD) induced by a high-fat diet (HFD) and its underlying mechanisms. In vivo HFD-induced CKD mouse models and in vitro OA/PA-stimulated HK2 cells were treated with AA. AA improved kidney morphology, reduced fibrosis, lipid accumulation, and body weight. It also decreased serum TC, TG, HDL-C, Scr, BUN, and Cys-C levels, indicating improved renal function. AA alleviated oxidative stress, ROS accumulation, and inflammation, as confirmed by DHE staining, oxidative stress markers, and pro-inflammatory cytokine levels. Western blotting showed that AA activated Nrf2 and suppressed NF-κB signaling. AMPK inhibition experiments demonstrated that AA regulated Nrf2 and NF-κB via AMPKα phosphorylation. In conclusion, AA mitigates HFD-induced CKD by targeting AMPKα to regulate oxidative stress and inflammation.

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Fengmao An,Xinran Xuan,Zheng Liu,Ming Bian,Qingkun Shen,Zheshan Quan,Guowei Zhang,Chengxi Wei

Alzheimer’s disease (AD) is a major neurodegenerative disease, but so far, it can only be treated symptomatically rather than changing the process of the disease. Recently, triazoles and their derivatives have been shown to have potential for the treatment of AD. In this study, the neuroprotective effects of 4-(4-(heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (W112) against β-amyloid (Aβ)-induced AD pathology and its possible mechanism were explored both in vitro and in vivo. The results showed that W112 exhibits a neuroprotective role against Aβ-induced cytotoxicity in PC12 cells and improves the learning and memory abilities of Aβ-induced AD-like rats. In addition, the assays of the protein expression revealed that W112 reversed tau hyperphosphorylation and reduced the production of proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, both in vitro and in vivo studies. Further study indicated that the regulation of mitogen-activated protein kinase/nuclear factor-κB pathways played a key role in mediating the neuroprotective effects of W112 against AD-like pathology. W112 may become a potential drug for AD intervention.Keywords:triazoles;Alzheimer’s disease;amyloid beta-peptides;neuroinflammation;mitogen-activated protein kinase/NF-kappa B signaling pathways

UV/Fe(II) synergistically activated S(IV) per-treatment on HA-enhanced Ca2+ scaling in NF filtration: Fouling mitigation, mechanisms and correlation analysis of membrane resistance in different filtration stage

Wenkai Liu,Bin Liu,Xin Li

The aim of this study was to investigate the feasibility and fouling mitigation mechanisms of UV/Fe(II) synergistically activated sulfite (S(IV)) (UFS) pretreatment to alleviate membrane fouling caused by HA-enhanced Ca 2+ scaling. After UFS treatment, hydrophobic substances and carboxyl groups structure were destroyed by the in-situ-generated SO•–4, resulted in a significant reduction of hydrophobic substances ratio and carboxyl group concentration. Due to the formation of more electropositive in-situ-generated Fe(III), the complexation between Ca 2+ and carboxyl groups was weakened so that the bulk crystallization size on the membrane surface was greatly reduced. The filter cake enhanced osmotic pressure effect (CEOP) and concentration polarization effect were hence alleviated, as well as the surface roughness . At the microcosmic perspective, as the energy barrier between the membrane and foulants was increased significantly after pretreatment, the anti -foulants adsorption ability of the membrane was enhanced. Correlation analysis showed that the carboxyl concentration and density, HPO ratio, larger particle size (>100 nm) ratio, the Ca 2+ concentration in the scaling layer and energy barrier all had a good correlation with the membrane resistance. This research not only provides an advanced oxidation technology that can effectively alleviate the synergistically-fouling effect of HA and Ca 2+ of nanofiltration process, but also proposes a guidance for the UV/Fe(II) synergistically activated sulfite.

The ameliorating effects of Guizhi Fuling Wan combined with rosiglitazone in a rat ovarian model of polycystic ovary syndrome by the PI3K/AKT/NF-κB and Nrf2/HO-1 pathways

Yongju Ye,Weimei Zhou,Yuefang Ren,Jiali Lu,Aixue Chen,Ruiying Jin,Feilan Xuan

Isoliquiritigenin suppresses IL-1β induced apoptosis and inflammation in chondrocyte-like ATDC5 cells by inhibiting NF-κB and exerts chondroprotective effects on a mouse model of anterior cruciate ligament transection

Baochao Ji,Wentao Guo,Hairong Ma,Boyong Xu,Wenbo Mu,Zhendong Zhang,Abdusami Amat,Li Cao

Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been demonstrated to exert attenuation of the nuclear factor-κB (NF-κB) signaling pathway and anti-inflammatory activity in a wide variety of cells. In the present study, the authors first evaluated the effects of ISL on cartilage degeneration in interleukin-1β (IL-1β)-stimulated chondrocyte-like ATDC5 cells and in a mouse model of osteoarthritis (OA). The data of a cell counting kit-8 and flow cytometry assay indicated that ISL suppressed the inhibitory effect of IL-1β on cell viability. The mRNA and protein expression levels of cyclooxygenase-2 and matrix metalloproteinase-13 were significantly decreased, while the expression of collagen II was increased, as indicated by RT-qPCR and western blot analysis following the chondrocyte-like ATDC5 cells were co-intervened with IL-1β and ISL for 48 h. Also, ISL attenuated protein expressions level of pro-apoptotic Bax, cleaved-caspase-3 and cleaved-caspase-9 and promoted expression of anti-apoptotic Bcl-2. Moreover, ISL inhibited NF-κB p65 phosphorylation induced by IL-1β. In addition, ISL also increased improved the thickness of hyaline cartilage and the production of proteoglycans in the cartilage matrix in a mouse OA model. These results indicated that ISL exerted anti-inflammatory and anti-apoptotic effects on IL-1β-stimulated chondrocyte-like ATDC5 cells, which may be associated with the downregulation of the NF-κB signaling pathway. In this way, the data supported the conclusion that ISL may be a novel potential preventive agent suitable for use in OA therapy.