查找使用阿拉丁产品的科研文献

Polydatin alleviates hyperuricemia combined with gouty arthritis in mice via regulating urate transporters, NLRP3 inflammasome and NF-κB pathway

Wenjing Xu,Yufeng Chen,Fenfen Li,Xiaoxi Zhang,Cantao Li,Chenxi Wu,Yan Huang,Daozong Xia

Gout is a metabolic disease that seriously affects people's health. Polydatin, a stilbene compound isolated from Polygonum cuspidatum , has attracted much attention because of its rich biological activity and high safety. This study aimed to investigate the therapeutic effect and mechanism of polydatin on hyperuricemia (HUA) combined with gouty arthritis (GA). The results showed that polydatin reduced the levels of uric acid and inflammatory cytokines, indicating that polydatin had the effect of reducing uric acid and anti-GA. Then the inhibitors of ABCG2, NLRP3 inflammasome and NF-κB pathway (Ko143, MCC950 and QNZ) were used to demonstrate that polydatin played a role in reducing uric acid and anti-GA via regulating urate transporters, NLRP3 inflammasome and NF-κB pathway. Taken together, these results provided evidence that polydatin might be used as a potential functional ingredient for the synchronous treatment of HUA and GA.

Rhoifolin attenuates atopic dermatitis-like symptoms in mice by regulating PPARα-mediated NF-κB/NLRP3 inflammation and pyroptosis processes

Hui Li,Hengli Luo,Xin Zhang,Jianchun Luo,Chenglin Zhan,Xiaofang Gong,Minghua Liu,Xiangfeng Chen,Ge Zhao

Rhoifolin alleviated pathological and histological changes in DNCB-induced Balb/c mice with AD-like responses. • Rhoifolin suppressed pro-inflammatory chemokine and cytokine production in TNF-α/IFN-γ-stimulated HaCaT cells. • Rhoifolin regulated skin barrier function and inflammation via PPARα-mediated NF-κB/NLRP3 pyroptosis signaling. Rhoifolin (ROF), a naturally occurring flavonoid glycoside, has been documented to possess a broad spectrum of biological properties, including anticancer, antioxidant, neuroprotective, hepatoprotective, anti-inflammatory, and antiviral activities. Atopic dermatitis (AD) is a persistent, recurring inflammatory skin illness that frequently greatly compromises the patients' quality of life. Nevertheless, the role of ROF in AD pathogenesis and the associated molecular events have yet to be elucidated. Our findings revealed that ROF administration substantially ameliorated the 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like phenotypes, as reflected by decreased mast cell accumulation, reduced CD4 + and CD8 + T cells infiltration within lesional skin, lowered serum immunoglobulin E (IgE) concentrations, attenuated epidermal and dermal thickening, suppressed histamine liberation and pruritic episodes, improved SCORAD indices, concomitant restoration of skin barrier protein expression, and curtailed the production of multiple inflammatory factors. Mechanistic investigations, integrating network pharmacology forecasts, transcriptomic profiling, and pharmacological blockade experiments with specific antagonists, further confirmed that the anti-inflammatory action of ROF operates through the PPARα-regulated NF-κB/NLRP3 signaling cascade. Collectively, these observations demonstrate that ROF exerts favorable inhibitory effects against AD-like inflammation both in vivo and in vitro , underscoring its potential as a viable therapeutic option for managing AD and other inflammatory cutaneous disorders. Download: Download high-res image (81KB) Download: Download full-size image

Integrated Identification of Macrophage NF-κB, p38 MAPK and AKT1 Signalling as Candidate Targets of Zerumbone in Experimental Periodontitis

Characterised by progressive alveolar bone loss, periodontitis arises from immune dysregulation and is classified as a chronic inflammatory condition. Zerumbone (Zer) has anti-inflammatory properties; however, its mechanism within the periodontal context remains unclear. We investigated the therapeutic effects and potential molecular targets of Zer by integratingin vivoefficacy assessment (using male C57BL/6 mice), network pharmacology, molecular docking, and molecular dynamics simulations, together with analysis of public single-cell transcriptomic data, with mechanistic validation using RAW 264.7 macrophages stimulated with LPS. In vivo, Zer attenuated bone resorption, preserved collagen integrity, reduced the number of TRAP-positive osteoclasts, and mitigated inflammation without hepatorenal toxicity. Network pharmacology predictedNFKB1,MAPK14, andAKT1as potential core targets, while IL-17 pathway enrichment suggested the involvement ofIL17A; single-cell data localisedNFKB1/MAPK14/AKT1to macrophages and showed thatIL17Ais predominantly expressed in T cells. In vitro, Zer dose-dependently suppressed LPS-driven phosphorylation of NF-κB p65, p38 MAPK and AKT1, correlating with reduced pro-inflammatory cytokine release and an M1-to-M2 phenotypic shift. In vivo, Zer also reduced gingival IL-17A expression. However, as IL-17A is primarily produced by T cells and our in vitro experiments were conducted exclusively in macrophages, this observation remains correlative and does not establish a direct T-cell-mediated effect. Collectively, these findings suggest that Zer ameliorates periodontitis partly through suppression of macrophage NF-κB and p38 MAPK signalling, with reduced AKT1 phosphorylation observed alongside these effects; however, whether AKT1 causally contributes to these effects remains to be determined. In addition, the potential impact on T-cell-associated IL-17A responses warrants further investigation.

Quercetin dietary supplementation protects against difenoconazole-induced carp spleen inflammatory damage via regulating ROS/NF-κB/NLRP3 inflammasome axis

Enzhuang Pan,Huimiao Feng,Zuwang Yang,Yue Xin,Xiaomeng Ji,Kaixin Ping,Yong Sun,Jingquan Dong

As a widely used fungicide at present, difenoconazole can enter the aquatic ecosystem and cause adverse effects on freshwater carp culture. The spleen, an important immune organ of carp, is vulnerable to damage by environmental toxins. Studies have shown that the inflammatory response is an important mechanism of immunotoxicity of difenoconazole. Whereas quercetin has anti-inflammatory pharmacological activity, the role and mechanism of quercetin in difenoconazole-induced inflammatory damage in the spleen of carp is unknown. In this study, we developed a model for carp with quercetin added to the diet and exposed to environmentally relevant concentrations of difenoconazole. We found that quercetin protects against inflammatory damage in the splenic tissue of carp through histopathological observations. We found that quercetin alleviated ROS enrichment and disruption of redox homeostasis (dynamic balance of GSH, T-AOC, CAT, and MDA) in the spleen tissue of carp by fluorescence assay and biochemical assay. We found that quercetin was able to inhibit the activation of the NF-κB signaling pathway (elevated p-NF-κB p65 expression level) and NLRP3 inflammasome pathway (NLRP3/ASC/caspase-1) in carp spleen tissue induced by difenoconazole by immunohistochemistry and qPCR analysis. In conclusion, this study confirms that the addition of quercetin as a supplement to the diets of freshwater cultured carp is effective against the spleen toxicity induced by difenoconazole. Mechanistically, quercetin may alleviate the difenoconazole-induced splenic inflammatory injury in carp by suppressing the excessive activation of ROS/NF-κB/NLRP3 inflammasome axis, providing new insights into the mechanism of quercetin alleviation of splenic inflammatory injury in carp.

Acetylation-stabilized chloride intracellular channel 1 exerts a tumor-promoting effect on cervical cancer cells by activating NF-κB

Wang Wanyue,Li Xin,Xu Ye,Guo Weikang,Yu Hui,Zhang Lu,Wang Yaoxian,Chen Xiuwei

Purpose Cervical cancer remains a major cause of cancer-related death in women, especially in developing countries. Previously, we found that the acetylation levels of chloride intracellular channel 1 (CLIC1) at lysine 131 were increased in cervical cancer tissues using a label-free proteomics approach. The aim of this study was to further determine the role of CLIC1 expression and its acetylation in cervical cancer. Methods CLIC1 expression and its implications for the prognosis of cervical cancer were analyzed using primary patient samples and cells, and the Gene Expression Profiling Interactive Analysis (GEPIA) database (gepia.cancer-pku.cn). The effect of CLIC1 on cervical cancer cells was evaluated using Cell Counting Kit (CCK)-8, flow cytometry, scratch wound healing, transwell, Western blotting and co-immunoprecipitation (Co-IP) assays. In vivo tumor growth was assessed using mouse xenograft models. Results We found that CLIC1 expression was increased in cervical cancer tissues and cells and that patients with a high CLIC1 expression tended to have a shorter overall survival time. Knockdown of CLIC1 significantly reduced in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumorigenesis. At the molecular level, we found that nuclear factor kappa B (NF-κB) activity was positively regulated by CLIC1. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, attenuated the tumor-promoting effect of CLIC1. Moreover, we found that CLIC1 acetylation at K131 was upregulated in cervical cancer cells, which stabilized CLIC1 by inhibiting its ubiquitynation. Substitution of K131 inhibited CLIC1 ubiquitynation and promoted in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumor growth. In addition, we found that acetyltransferase HAT1 was responsible for CLIC1 acetylation at K131. Conclusion Our data indicate that CLIC1 acts as a tumor promoter in cervical cancer, suggesting a potential treatment strategy for cervical cancer by regulating CLIC1 expression and/or acetylation.

Kaempferol from Penthorum chinense Pursh suppresses HMGB1/TLR4/NF-κB signaling and NLRP3 inflammasome activation in acetaminophen-induced hepatotoxicity

Yi-Chao Du,Li Lai,Hao Zhang,Fu-Rui Zhong,Huan-Li Cheng,Bao-Lin Qian,Peng Tan,Xian-Ming Xia,Wen-Guang Fu

Acetaminophen (APAP) is one of the safest and most effective over-the-counter (OTC) analgesics and antipyretics, but excessive doses of APAP will induce hepatotoxicity with high morbidity and mortality worldwide. Kaempferol (KA), a flavonoid compound derived from the medicinal and edible plant of Penthorum chinense Pursh, has been reported to exert a profound anti-inflammatory and antioxidant activity. In this study, we explored the protective effect and novel mechanism of KA against APAP-induced hepatotoxicity. The results revealed that KA pretreatment significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), relieved hepatocellular damage and apoptosis, attenuated the exhaustion of glutathione (GSH) and accumulation of malondialdehyde (MDA), increased the expression of antioxidative enzymes (e.g., heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1)), and thus restrained APAP-induced oxidative damage in the liver. KA suppressed the expression of NLRP3 and reduced the levels of pro-inflammatory factors, including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Moreover, KA remarkably inhibited high-mobility group box 1 (HMGB1) and toll-like receptor 4 (TLR4) expression as well as nuclear factor kappa-B (NF-κB) activation for liver protection against APAP-induced inflammatory responses and apoptosis. Taken together, our findings suggested that KA could effectively protect hepatocytes from APAP hepatotoxicity through the up-regulation of HO-1 and NQO1 expression, the down-regulation of NLRP3 expression, and the inhibition of the HMGB1/TLR4/NF-κB signaling pathway.

In-situ preparation and excellent performance of Co9S8/C/NF with binder-free as anodes for lithium-ion batteries

Chengli Yao,Jianglin Xu,Anjian Xie,Yuhua Shen

Nowadays, developing new anode material for lithium-ion batteries (LIBs) with distinguished electrochemical properties is still very significant and a huge challenge. Herein, a nanocomposite containing Co 9 S 8 /carbon (C)/nickel foam (NF) was synthesized. In the preparation process, ZIF-67 as the source of both Co 2+ and carbon was designedly grown in situ on the surface of NF with loose porous skeleton through the hydrothermal reaction. After sulfurization and pyrolysis of ZIF-67/NF, the porous flower-like Co 9 S 8 /C/NF composites formed. As a binder-free anode, Co 9 S 8 /C/NF exhibited excellent lithium storage performance, which showed a superior initial discharge capacity of 1926 mA h g −1 and reversible capacity of 1114 mA h g −1 after 200 cycles at 0.2 A g −1 . Even at 2 A g −1 current density, it could maintain a capacity of 578 mA h g −1 . The above outstanding electrochemical performances may be due to the following reasons. The loose flower-like structure assembled by lots of nanosheets, can provide a larger surface area for the transport and storage of Li + ions. With the cooperation of carbon matrix, the volume expansion of anodes can be effectively alleviated during charge and discharge process. At the same time, metal nickel foam as the current collector of the negative electrode also can increase the conductivity; promote the transport and diffusion of electrons. The loose skeleton enables the full contact of the active material with the electrolyte, which is beneficial to the transportation of Li + ions and electronics. This work provides an inspiration for designing and fabricating anode materials with distinguished-performance for LIBs.

Hepatoprotective Effect of Apigenin Against Liver Injury via the Non-canonical NF-κB Pathway In Vivo and In Vitro

Yue Shuwen,Xue Ning,Li Honglei,Huang Baosheng,Chen Zhen,Wang Xing

Apigenin, a flavonoid found in many plants, has various biological properties. We aimed to investigate the anti-inflammatory and anti-oxidative activity of apigenin against carbon tetrachloride (CCl 4 )-induced acute liver injury in mice and hydrogen peroxide (H 2 O 2 )-induced oxidative stress in HepG2 cells and possible mechanism. In vivo , apigenin significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in serum of mice challenged by CCl 4 and markedly alleviated the lipid peroxidation as indicated by the increased level of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidases (GSH-Px) and catalase (CAT), and the decreased malondialdehyde (MDA) in liver tissue. Apigenin also ameliorated inflammation by downregulating tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and upregulating IL-10. Consistently, the elevated ALT and AST level; the impaired balance between SOD, GSH activity, and excessive ROS; and the increased gene expression of TNF-α and IL-6 resulting from H 2 O 2 -induced oxidative stress were restored by apigenin. Moreover, the results from Western blot, real-time qPCR, and immunofluorescence assay indicated that apigenin enhanced the activity of TNF receptor-associated factor (TRAF) 2/3 and cellular inhibitor of apoptosis protein (c-IAP) 1, ameliorated NF-κB-inducing kinase (NIK), and mediated the nuclear translocation of NF-κB2, therefore had an inhibitory effect on the non-canonical NF-κB pathway which was activated in both models. siNIK canceled the protective effect of apigenin on H 2 O 2 -induced HepG2 cells. Altogether, our results demonstrated that apigenin mitigated liver injury by ameliorating inflammation and oxidative stress through suppression of the non-canonical NF-κB pathway, indicating the potential of apigenin for treatment of the liver injury.

Tuning the nano-porosity and nano-morphology of nano-filtration (NF) membranes: Divalent metal nitrates modulated inter-facial polymerization

Xiumin Zhang,Wenjie Yang,Qingyi Wang,Fei Huang,Congjie Gao,Lixin Xue

Divalent metal nitrates were pre-loaded on polysulfone support to modulate the interfacial polymerization between piperazine (PIP) and trimesoyl chloride (TMC). It is found that the nano-porosity and nano-morphology of thus formed thin film composite polyamide (TFC-PA) nano-filtration (NF) membranes as well as their filtration performance could be effectively tuned by the type and concentration of the divalent metal salts, especially the divalent cations used. Main group cations, such as Mg (II) and Ca (II), increased the water flux of the NF membranes by increasing their surface nano-scale nodular arrays without altering the pore sizes and rejections of the membranes, while transitional metal cations such as Zn (II), Cu (II) and Co (II) increased the water flux of the NF membranes not only by the formation of high surface area nano-scale Turing type crisscrossed ridge networks, but also by the increase of their nano-pore sizes due to their coordination with the >NH groups of the PIP. The prepared NF membranes pore sizes adjustable from 0.54 Å to 0.90 Å could be developed to have varied selectivity and rejections among inorganic salts and organic dyes.

CLG from Hemp Seed Inhibits LPS-Stimulated Neuroinflammation in BV2 Microglia by Regulating NF-κB and Nrf-2 Pathways

Shanshan Wang,Qian Luo,Yuefang Zhou,Peihong Fan

The healthy benefits of hemp (Cannabis sativa L.) seed have often been attributed to its oils and proteins. Recent studies reveal that hemp seed phenylpropionamides could also show various bioactivities. Continuation of our study on hemp seed provided a phenylpropionamide, coumaroylaminobutanol glucopyranoside (CLG). This work investigated the neuroprotective effect of CLG and its underlying mechanism using lipopolysaccharide-induced BV2 microglia. Our study demonstrated that CLG increased adenosine monophosphate-activated protein kinase (AMPK) expression, suppressed the nuclear factor-kappa B (NF-κB) signaling pathway by inhibiting the phosphorylation of IκBα and NF-κB p65 and decreased proinflammatory cytokine levels in a concentration-dependent manner. Furthermore, CLG reduced the production of cellular reactive oxygen species and stimulated the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway. Collectively, these results suggested that CLG effectively and simultaneously inhibited inflammatory responses and oxidative stress through the NF-κB and Nrf-2 signaling pathways. AMPK was also involved in the anti-inflammatory effect of CLG. This study provides new insights into the diverse bioactive constituents of hemp seed.

Indole-2-Carboxamide Derivative LG25 Inhibits Triple-Negative Breast Cancer Growth By Suppressing Akt/mTOR/NF-κB Signalling Pathway

Xiaohong Xu,Vinothkumar Rajamanickam,Sheng Shu,Zhoudi Liu,Tao Yan,Jinxin He,Zhiguo Liu,Guilong Guo,Guang Liang,Yi Wang

Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer which is associated with poor patient outcome and lack of targeted therapy. Our laboratory has synthesized a series of indole-2-carboxamide derivatives. Among this series, compound LG25 showed a favorable pharmacological profile against sepsis and inflammatory diseases. In the present study, we investigated the chemotherapeutic potential of LG25 against TNBC utilizing in vitro and in vivo models. Methods Changes in cell viability, cell cycle phases and apoptosis were analyzed using MTT, clonogenic assay, FACS and Western blotting assays. The anti-cancer effects of LG25 were further determined in a xenograft mouse model. Results Our findings reveal that LG25 reduced TNBC viability in a dose-dependent manner. Flow cytometric and Western blot analyses showed that LG25 enhances G2/M cell cycle arrest and induced cell apoptosis. In addition, LG25 treatment significantly inhibited Akt/mTOR phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB). These inhibitory activities of LG25 were confirmed in mice implanted MDA-MB-231 TNBC cells. Conclusion Our studies provide experimental evidence that indole-2-carboxamide derivative LG25 effectively targeted TNBC in preclinical models by inducing cell cycle arrest and apoptosis, through suppressing Akt/mTOR/NF-κB signaling pathway.

The 3D ultra-thin Cu1-xNixS/NF nanosheet as a highly efficient and stable electrocatalyst for overall water splitting

Ying Li,Hui Su,Jianpeng Fu,Xiaoqiang Du

In recent years, the exploration of efficient and stable noble-metal-free electrocatalysts is becoming increasingly important, used mainly for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). In this work, a new ultrathin porous Cu 1-x Ni x S/NF nanosheets array was constructed on the 3D nickel skeleton by two-step method: hydrothermal method and vulcanization method. Through these two processes, Cu 1-x Ni x S/NF has a larger specific surface area than that of foamed nickel (NF) and Cu 1-x Ni x O/NF. The Cu 1-x Ni x S/NF materials show excellent catalytic activity by accelerating the electron transfer rate and increase the amount of H 2 and O 2 produced. The lower overpotential was obtained only 350 mV at 20 mA cm −2 for OER, not only that, but also the same phenomenon is pointed out in HER, optimal Cu 1-x Ni x S/NF presents low overpotentials of 189 mV to reach a current density of 10 mA cm −2 in 1.0 M KOH for HER. Both OER and HER shows a lower Tafel slope: 51.2 mV dec −1 and 127.2 mV dec −1 , subsequently, the overall water splitting activity of Cu 1-x Ni x S/NF was investigated, and the low cell voltage was 1.64 V (current density 10 mA cm −2 ). It can be stable for 14 h during the overall water splitting reaction. These results fully demonstrate that Cu 1-x Ni x S/NF non-precious metal materials can be invoked become one of the effective catalysts for overall water splitting, providing a richer resource for energy storage.