Applied Materials Today
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2020
·
IF 8.352
Qiongcong Xu,Liying Wang,Tong Tong,Xitai Huang,Chensong Huang,Fuxi Li,Qiao Su,Yichih Tien,Jun Wu,Wei Zhao,Xiaoyu Yin
Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract diseases with limited therapeutic strategies and poor prognosis. Various therapeutic agents have been demonstrated effective in preclinical models, but high dose requirement and toxicity to normal cells limit their clinical applications. Considering the high concentration of glutathione (GSH) in GBC, we developed a GSH-responsive nanoparticle (NP) system based on biodegradable poly(disulfide amide) (Cys-8E Polymer) for targeted delivery of a BRD4 inhibitor (JQ1), which is known as a promising therapeutic agent for GBC treatment. JQ1-loaded Cys-8E nanoparticles ( [email protected] NPs) possessed a high JQ1 loading, preferable stability and redox-responsive release behavior. Additionally, the NPs showed good targeted delivery into GBC tumor spheroids and GBC patient-derived xenograft (PDX) tumors. Specifically, the intracellular GSH in tumors could trigger the release of JQ1, which induced the cell cycle arrest and apoptosis of GBC cells. RNA-sequencing analysis revealed that [email protected] NPs enhanced the effect of JQ1 through inhibiting NF-κB pathway. Importantly, [email protected] NPs significantly suppressed GBC tumor growth in the PDX model of early recurrence. No obvious systemic toxicity and organ damages were observed after treatment with [email protected] NPs. Our results demonstrate the promising therapeutic applications of [email protected] NPs for adjuvant therapy in GBC treatment.
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Cancer Management and Research
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2020
·
IF 2.886
Weixu Luo,Yuanshan Han,Pan Meng,Qin Yang,Hongqing Zhao,Jia Ling,Yuhong Wang
Background Breast cancer is one of the most common cancer with high risk in females all over the world. It is usually complicated with depression, which can further accelerate the development and progression of breast tumors. We aim to identify a new drug and identify its functional mechanism in the regulation of hippocampal microglia (MG) in breast cancer complicated with depression (BCCD). Methods The activation model of MG was established by treatments from corticosterone (CORT) or lipopolysaccharides (LPS). The inhibitory effects of resatorvid on MG were investigated by CCK-8, ROS, immunofluorescence, TUNEL, scratch test, ELISA, RT-qPCR and Western blot. BCCD animal model was established using 4T1 inflammatory breast cancer cells and CORT treatment in vitro. Open field experiment (OFE), tail suspension test (TST), ELISA, RT-qPCR and Western blot experiments were utilized to examine the effects of resatorvid on the animal model in vivo. Results The cell viability and migration ability of the BCCD model group were suppressed. The expressions of inflammatory factors, ROS, and the apoptotic rate of the BCCD model group were up-regulated, in contrast to the control group. The expressions related to the TLR4/NF-κB/NLRP3 signaling in the BCCD model group were also elevated. Resatorvid reversed the above changes, which showed good therapeutic effects in depression-related behavioral changes, tumor treatment, and blood–brain barrier function. Conclusion In summary, resatorvid inhibited the activation of hippocampal MG in BCCD by regulating TLR4/NF-κB/NLRP3 signaling pathway.
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INFLAMMATION
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2020
·Vol. 44
·期 2
·746-757
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IF 3.212
Gao Yang,Kang Kai,Liu Yan-song,Li Na-na,Han Qiu-yuan,Liu Hai-tao,Kong Wei-lan,Zhang Xing,Huang Rui,Yang Zhen-yu,Qi Zhi-dong,Zheng Jun-bo,Li Ming,Wang Hong-liang,Li Jia-yu,Liu Rui-jin,Wang Si-cong,Zhang Wei-hua,Zhao Ming-yan,Yu Kai-jiang
This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.
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CHEMOSPHERE
·
2020
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IF 5.778
Chao Fang,Tian Ou,Xingyu Wang,Min Rui,Wenhai Chu
Ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) are widely used in drinking water treatment and wastewater recycling. However, limited information was available regarding their performance in removing trihalomethanes (THMs). The present study investigated the effect of feed solution characteristics and membrane fouling on THM removal by UF/NF/RO membranes. The results indicated that THMs were poorly removed by UF membrane, and the removal was dominated by hydrophobic adsorption. In contrast, high removal of THMs was observed for NF/RO membranes, which was contributed by both size exclusion and hydrophobic adsorption. By comparing the adsorption of THMs on NF/RO membranes at different feed concentration, it was found that the role of hydrophobic adsorption was more important at lower feed concentration. The removal of THMs by UF/NF/RO membranes increased with increasing feed concentration, which can be ascribed to the enhanced diffusion at higher concentration gradient. With increasing ionic strength, THM removal was decreased significantly for UF membrane, but the removal by NF/RO membranes remained largely unchanged. By comparing THM removal by clean and fouled membranes, the effect of membrane fouling was examined. The removal of most THMs (except trichloromethane) decreased after fouling for UF membrane, whereas decreased removal was only observed for iodinated THMs for fouled NF/RO membranes.
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CELL CYCLE
·
2021
·
IF 4.534
Limei Yan,Zeping He,Wei Li,Ning Liu,Song Gao
Rhophilin Rho GTPase binding protein 2 (P76RBE) belongs to rhophilin family of Rho-GTPase-binding proteins and is found to contribute to the development of diverse cancers. Data in Oncomine and Kaplan–Meier Plotter databases showed that P76RBE was upregulated in ovarian cancer tissues compared with normal tissues, and patients with high P76RBE expression had worse overall survival, which indicated P76RBE may be associated with the pathogenesis of ovarian cancer. This study aimed to investigate the role of P76RBE in ovarian cancer and to reveal the possible underlying mechanisms. The results demonstrated that P76RBE was highly expressed in ovarian cancer tissues and ovarian cancer cell lines. Functionally, silencing of P76RBE suppressed the proliferation, induced cell cycle arrest, and inhibited migration and invasion in OVCAR-3 and OV-90 cells, while overexpression of P76RBE showed opposite effects on A2780 cells. Mechanically, P76RBE silencing resulted in downregulation of integrin β1, accompanying the reduced NF-κB p65 phosphorylation and nuclear translocation. Importantly, integrin β1 knockdown effectively rescued the effects of P76RBE overexpression on ovarian cancer cells with suppressed proliferation, migration, and invasion. Additionally, in the xenograft tumors derived from OVCAR-3 and OV-90 cell lines, P76RBE knockdown inhibited tumor growth. Meanwhile, the expression of integrin β1 and NF-κB p65 phosphorylation was decreased. In summary, our findings indicate that P76RBE contributes to the progression of ovarian cancer through regulating the integrin β1/NF-κB signaling, and it may be a promising target for ovarian cancer therapy.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2019
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IF 5.107
Luhong Zhang,Hongfang Guan,Na Zhang,Bin Jiang,Yongli Sun,Na Yang
In this study, a high flux loose nanofiltration (NF) membrane was fabricated for the desalination of dye wastewater through a facile method which combined doping and surface grafting. First, PES ultrafiltration substrate was prepared via non-solvent induced phase separation by introducing multi-hydroxyl β-cyclodextrin (β-CD) into the casting solution as hydrophilic additive. Then, titanium dioxide (TiO 2 ) nanoparticles were grafted uniformly on membrane surface with the assistance of 1, 6-hexamethylene diisocyanate (HMDI), resulting in the enhancement of surface hydrophilicity and separation performance of the resultant membranes. Remarkably, the membrane prepared at optimized conditions achieved a high pure water flux (52.0 L·m −2 ·h −1 at 0.2 MPa) and high permeate flux for dyes (e.g. 30.5 L·m −2 ·h −1 for Congo Red at 0.2 MPa). It also exhibited high rejection for dyes (e.g. 97.4% for Congo Red) and high transmittance of salts (e.g. 94.0% for Na 2 SO 4 ). Moreover, the membrane possessed good antifouling performance with a high flux recovery ratio of 93.7% after fouled by humic acid (HA). The results indicated that the novel loose NF membrane had an impressive potential application for dye wastewater treatment.
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Frontiers in Pharmacology
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2019
·
IF 3.845
Linghu Ke-Gang,Wu Guo-Ping,Fu Ling-Yun,Yang Hong,Li Hai-Zhi,Chen Yan,Yu Hua,Tao Ling,Shen Xiang-Chun
1,8-Cineole (eucalyptol), a monoterpene, has been widely reported for the anti-inflammatory effects. Our previous data confirmed that 1,8-cineole ameliorated the inflammatory phenotype of human umbilical vein endothelial cells (HUVECs) by mediating NF-κB expression in vitro. At present, we investigated the protection effects of 1,8-cineole on vascular endothelium in lipopolysaccharide (LPS)-induced acute inflammatory injury mice and the potential mechanisms involved in the protection in HUVECs. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed the secretion of interleukin (IL)-6 and IL-8 and increased the expression of IL-10 in the serum of LPS-induced mice. 1,8-Cineole reduced the inflammatory infiltration and the expression of vascular cell adhesion molecular 1 (VCAM-1) in the sections of thoracic aorta in LPS-induced acute inflammatory mice. Western blotting indicated that 1,8-cineole significantly decreased the phosphorylation of NF-κB p65 and increased the expression of PPAR-γ in the thoracic aorta tissue. 1,8-Cineole increased the expression of PPAR-γ in LPS-induced HUVECs. 1,8-Cineole and rosiglitazone reduced the protein and mRNA levels of VCAM-1, E-selectin, IL-6, and IL-8 in LPS-induced HUVECs, which could be reversed by the action of GW9662 (inhibitor of PPAR-γ). 1,8-Cineole and rosiglitazone blocked the LPS-induced IκBα degradation and NF-κB p65 nucleus translocation, which could be reversed by the pretreatment of GW9662 or silence of PPAR-γ gene. In conclusion, 1,8-cineole attenuated LPS-induced vascular endothelial cells injury via PPAR-γ dependent modulation of NF-κB.
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Food & Function
·
2018
·Vol. 9
·期 12
·6155-6164
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IF 3.289
Lang Zhang,Ya Fan,Hanwen Su,Li Wu,Yuying Huang,Lei Zhao,Bing Han,Guangwen Shu,Meixian Xiang,Jin-Ming Yang
The objective of this study was to investigate the anti-inflammatory effect of chlorogenic acid methyl ester (CME) and the molecular mechanism involved, through using non-infectious inflammation and infectious inflammation animal models as well as lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cell models. Our results demonstrated that CME markedly inhibited ear swelling, paw swelling and granuloma swelling, and decreased intraperitoneal capillary permeability in non-infectious inflammation. Moreover, CME significantly alleviated the pathological damage of the lung tissue, reduced the levels of PGE2 and IL-1β in the serum and the protein expression levels of related-inflammatory factors in the lung tissue of LPS-induced mice with acute lung injury (ALI). In addition, CME affected the RAW264.7 cell cycle and inhibited the protein expressions of COX-2 and NLRP3 and prevented the phosphorylation of NF-κB p65 in RAW264.7 cells treated with LPS. These observations not only validated the anti-inflammatory effects of CME, but also revealed the underlying molecular basis, which involves the down-regulation of the expression of inflammatory factors and blockade of the COX-2/NLRP3/NF-κB signaling pathway.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Yuzhu Ye,Yuanlu Shan,Caiying Bao,Yi Hu,Liangrong Wang
Background/aims Ginsenoside Rg1 is regarded as the primary bioactive ingredient in Panax notoginseng that has been well recognized for its protective effects against ischemia/reperfusion (IR) injury. However, the mechanisms still remain elusive. Our study aims to investigate the effects of Rg1 against lung injury induced by hind-limb IR in rats. Methods Twenty-four Sprague Dawley rats were randomly submitted to sham operation (SM group), hind-limb IR (IR group), hind-limb IR + Rg1 (Rg1 group), and hind-limb IR + Pro-DTC group (PD group). All the rats except those in SM group were subjected to 3 h of ischemia followed by 6 h of reperfusion , and extra intravenous Rg1 and pyrrolidine dithiocarbamate (Pro-DTC), a selective inhibitor of nuclear factor kappa B (NF-κB), was administered intravenously before ischemia in the Rg1 and PD group, respectively. The activities of myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT), as well as protein expressions of NF-κB p65 and cyclooxygenases-2 (COX-2) in lung tissue, and thromboxane B2 (TXB2) and 6-keto-ProstaglandinF 1α (6-keto-PGF 1α ) levels in bronchoalveolar lavage (BAL) fluid were detected. Morphological changes, index of quantitative assessment of histologic lung injury (IQA), apoptosis index (AI) and lung Wet/Dry ratio were also evaluated. Results The levels of Wet/Dry ratio, IQA, AI, activities of MPO and 6-keto-PGF 1α /TXB 2 ratio were increased, and NF-κB p65 and COX-2 protein expression were upregulated, while SOD and CAT levels were decreased in lung tissue in IR group as compared with SM group ( p < 0.05), all the alterations could be significantly reversed by Rg1 or Pro-DTC pretreatment ( p < 0.05). And Rg1 and Pro-DTC also significantly attenuated the pulmonary histological abnormalities induced by IR. Conclusion Ginsenoside Rg1 potentially attenuated lung injury induced by hind-limb IR by regulating NF-κB/COX-2 signaling pathway .
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Biochemistry and Cell Biology
·
2017
·Vol. 95
·期 6
·
IF 1.895
Xilin Xu,Hang Lv,Xiaodong Li,Hui Su,Xiaofeng Zhang,Jun Yang
Danshen (Salvia miltiorrhiza) is a traditional Chinese medicine herb that can alleviate the symptoms of osteoarthritis (OA) (Söder et al. 2006) in animals. However, the underlying mechanisms remain poorly understood and require further investigation. In this study, rabbits with experimentally induced OA were given an intra-articular injection of danshen (0.7 mL/day) for 5 weeks. In addition to attenuating the cartilage degeneration of OA in the rabbits, danshen decreased the expression and activity of matrix metalloproteinase 9 (MMP-9) and MMP-13, and increased the expression of their natural inhibitors: tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and TIMP-2. Apoptosis in osteoarthritic cartilage tissues was attenuated by danshen, accompanied with increased expression of B cell lymphoma 2 (Bcl-2) and decreased levels of Bcl-2-associated X protein (Bax). Further, danshen inhibited the nuclear accumulation of nuclear factor kappa-B (NF-κB) p65 in osteoarthritic cartilage. The therapeutic effects of danshen in vivo were comparable to that of sodium hyaluronate, which is a drug used clinically for the treatment OA. In vitro, sodium nitroprusside (SNP) was used to stimulate apoptosis in primary rabbit chondrocytes. We found that the SNP-induced apoptosis was mitigated by danshen. BAY11-7028, an inhibitor of the NF-κB pathway, augmented danshen’s anti-apoptotic effects in cells exposed to SNP. When these results are considered together, they indicate that danshen alleviates the cartilage injury in rabbit OA through inhibition of the NF-κB signaling pathway.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2017
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IF 2.896
Han-bin Chen,Chao-dan Luo,Jia-li Liang,Zhen-biao Zhang,Guo-sheng Lin,Jia-zhen Wu,Cai-lan Li,Li-hua Tan,Xiao-bo Yang,Zi-ren Su,Jian-hui Xie,Hui-fang Zeng
Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema . The results exhibited that CFB exerted a dose-dependent suppression on ear edema induced by xylene, significantly mitigated the aggravation of vascular permeability caused by acetic acid and paw edema induced by carrageenan . Additionally, CFB significantly suppressed the productions of interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandinE2 (PGE 2 ) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared with the vehicle group after treatment with carrageenan. Signaling events of nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKβ, p-IκBα and p65 (nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα (IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB also significantly suppressed the mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK (phospho-extracellular signal-regulated kinase). Hence, CFB efficiently prevented inflammation, at least partially, via inhibition of NF-κB and MAPK pathways. These findings provided a pioneering pharmacological basis for the anti-inflammatory effect of CFB and suggested CFB might be a potential candidate for the therapy of inflammatory disorders.
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INORGANIC CHEMISTRY
·
2024
·
IF 4.3
Yue Yan,Wenrui Wu,Yang Yang,Tao Xu,Xianfu Li
The rational collocation and construction of multiphase composite electrode materials with ingenious structures is a key strategic to enhance the electrochemical performance of supercapacitors (SCs). Within this project, a unique Co9S8@CoAl-LDH/NF core–shell heterostructure consisting of CoAl-LDH/NF ultrathin nanosheets sturdily attached to Co9S8/NF needle-like nanorods is grown in situ on self-supported conductive substrate nickel foam (NF) by an effortless and productive multistep hydrothermal method. The construction of the core–shell structure can effectively enhance the capacitive properties as well as the mechanical strength of the material. Compared with the single-component materials Co9S8/NF (1769.6 mF cm–2 and 91.6%) and CoAl-LDH/NF (858 mF cm–2 and 85.2%), the Co9S8@CoAl-LDH/NF composites have excellent capacitance properties (5052.4 mF cm–2) along with exceptional capacitance retention (5000 cycles) 98.5% even after undergoing charging and discharging. Furthermore, the asymmetric SCs fabricated with Co9S8@CoAl-LDH/NF and AC/NF exhibit an energy density of 0.17 mWh cm–2 at 3.20 mW cm–2. Therefore, the innovative core–shell heterostructure of Co9S8@CoAl-LDH/NF presented in this study holds immense practical potential as a groundbreaking electrode material in the realm of SCs.
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