ACS Chemical Neuroscience
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2023
·
IF 5
Xiaoyi Shi,Meng Li,Qiming Huang,Liuming Xie,Zhibing Huang
Monacolin K (MK), a polyketo secondary metabolic compound of the mold genus Monascus, can promote the apoptosis of malignant cancer cells, possessing potential antitumor properties. However, its mechanism of action on gliomas remains unclear. Here, we explored and investigated the potential of the monacolin K’s antitumor effect on human glioma U251 cells and its possible molecular mechanism. Results showed that the application of 10 μM monacolin K inhibited the proliferation of U251 cells, with an inhibitory rate of up to 53.4%. Additionally, monacolin K induced the generation of reactive oxygen species and activated mitochondria-mediated pathways, including decreased MMP, activation of caspase3/caspase9, decreased Na+/K+-ATPase and Ca2+-ATPase activities, and disruption of the antioxidant system, resulting in the disruption of intracellular reduction–oxidation homeostasis. Monacolin K also activated MAPK and NF-κB pathways, upregulating P38 activity and downregulating JNK/ERK/P65/IκBα expression, ultimately leading to apoptosis of U251 cells. Importantly, monacolin K was not cytotoxic to normal human cells, hUC-MSCs. We concluded that monacolin K can induce apoptosis in U251 cells by triggering ROS-mediated oxidative damage and regulating MAPKs and NF-κB pathways.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Zhehuan Wang,Huiru Zhang,Caihong Qi,Hui Guo,Xiangyue Jiao,Jia Yan,Yifei Wang,Qiangsheng Li,Mingming Zhao,Xinhao Guo,Baoluo Wan,Xiaotian Li
Background Ursolic acid (UA) is a triterpenoid compound found in natural plants. It has been reported to have anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in atopic dermatitis (AD) is unknown. This study aimed to evaluate the therapeutic effect of UA in AD mice and explore the underlying mechanisms. Methods Balb/c mice were treated with 2, 4-dinitrochlorobenzene (DNCB) to induce AD-like lesions. During modeling and medication administration, dermatitis scores and ear thickness were measured. Subsequently, histopathological changes, levels of T helper cytokines, and oxidative stress markers levels were evaluated. Immunohistochemistry staining was used to assess changes in the expression of the nuclear factor of kappa B (NF-κB) and NF erythroid 2-related factor 2 (Nrf2). Furthermore, CCK8 assay, reactive oxygen species (ROS) assay, real-time PCR, and western blotting were employed to evaluate the effects of UA on ROS levels, inflammatory mediator production, and the NF-κB and Nrf2 pathways in TNF-α/IFN-γ-stimulated HaCaT cells. Results The results showed that UA significantly reduced dermatitis score and ear thickness, effectively inhibited skin proliferation and mast cell infiltration in AD mice, and decreased the expression level of T helper cytokines. Meanwhile, UA improved oxidative stress in AD mice by regulating lipid peroxidation and increasing the activity of antioxidant enzymes. In addition, UA inhibited ROS accumulation and chemokine secretion in TNF-α/IFN-γ-stimulated HaCaT cells. It might exert anti-dermatitis effects by inhibiting the TLR4/NF-κB pathway and activating the Nrf2/HO-1 pathway. Conclusion Taken together, our results suggest that UA may have potential therapeutic effects on AD and could be further studied as a promising drug for AD treatment.
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MOLECULAR NEUROBIOLOGY
·
2023
·Vol. 60
·期 7
·3824-3838
·
IF 5.1
Deng Ling,Zhang Jiyu,Chen Sha,Wu Yu,Fan Xiaomei,Zuo Tianrui,Hu Qingwen,Jiang Lu,Yang Shaonan,Dong Zhi
Blood-brain barrier (BBB) disruption can induce further hemorrhagic transformation in ischemic stroke (IS). miR-671-5p, a micro-RNA, is abundant in the cortex of mammalian brains. Herein, we investigated the roles and potential mechanisms for the effects of miR-671-5p on BBB permeability in IS. Results showed that miR-671-5p levels were significantly downregulated in the cerebral cortex of middle cerebral artery occlusion/reperfusion (MCAO/R) C57/BL6 mice in vivo . miR-671-5p agomir administration via right intracerebroventricular injection significantly reduced infarct volume, improved neurological deficits, the axon of neurons and nerve fiber, attenuated cell injury and apoptosis, as well as reduced BBB permeability in MCAO/R mice. Treatment with miR-671-5p agomir alleviated tight junction proteins degradation, including claudin, occludin, and ZO-1 in MCAO/R mice, and these effects were reversed following NF-κB overexpression. Bend.3 brain endothelial cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) treatment in vivo , and then miR-671-5p agomir was transfected into the cells. This resulted in reduction of cytotoxicity, improved cell viability, trans-endothelial electrical resistance, reduced fluorescein sodium permeability, and inhibited tight junction degradation in Bend.3 OGD/R cells. However, these effects were reversed following NF-κB overexpression. These results demonstrated that upregulation of miR-671-5p in IS models in vivo and i n vitro alleviated BBB permeability by targeting NF-κB/MMP-9. In summary, miR-671-5p is a potential therapeutic target for protecting BBB permeability in IS to minimize cerebral hemorrhage transformation.
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BIOMATERIALS
·
2023
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IF 14
Xiaojuan Xiao,Zekang Ma,Zhenzhen Li,Yiyi Deng,Yibin Zhang,Ruohong Xiang,Lin Zhu,Yilang He,Hui Li,Yu Jiang,Yu Zhu,Yifang Xie,Hongling Peng,Xifeng Liu,Haiqin Wang,Mao Ye,Yuetao Zhao,Jing Liu
Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile [email protected] @EM @anti-BCMA ( [email protected] ) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo . Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics.
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Materials Chemistry Frontiers
·
2023
·Vol. 7
·期 13
·2628-2636
·
IF 7
Lixia Wang,Meilin Huang,Mingcheng Gao,Tayirjan Taylor Isimjan,Xiulin Yang
Effective control of strong electron interaction at heterogeneous interfaces is crucial for the creation of highly efficient and stable bifunctional catalysts for water splitting. In this work, we synthesized an urchin-like CoP–Ce2(CO3)2O catalyst on nickel foam (CoP–Ce2(CO3)2O/NF) via a facile hydrothermal and gas-phase phosphating process, which enhances active site exposure and improves catalytic reaction kinetics. Spectroscopy analysis reveals that the enhanced performance is due to the charge transfer between CoP and Ce2(CO3)2O and the unique urchin-like structure of the hybrid catalyst. The CoP–Ce2(CO3)2O/NF catalyst showed excellent hydrogen/oxygen evolution reaction (HER/OER) performance (η10 = 85.2 and 205.5 mV) and robust long-term stability in 1.0 M KOH. Additionally, the CoP–Ce2(CO3)2O/NF(+)||CoP–Ce2(CO3)2O/NF(−) electrolyzer required only a low cell voltage of 1.82 V to produce 100 mA cm−2 for overall water splitting, outperforming most previous catalysts. This work presents a strategy for interfacial engineering to improve the activity of bifunctional heterojunction electrocatalysts for overall water splitting.
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Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 3
·e10475
·
IF 10.684
Chen Zhang,Zhengxiang Cheng,Yuanyuan Zhou,Ziyi Yu,Hongyu Mai,Changhao Xu,Jing Zhang,Jiali Wang
In patients with mild osteoarthritis (OA), two to four monthly injections are required for 6 months due to the degradation of hyaluronic acid (HA) by peroxidative cleavage and hyaluronidase. However, frequent injections may lead to local infection and also cause inconvenience to patients during the COVID-19 pandemic. Herein, we developed a novel HA granular hydrogel (n-HA) with improved degradation resistance. The chemical structure, injectable capability, morphology, rheological properties, biodegradability, and cytocompatibility of the n-HA were investigated. In addition, the effects of the n-HA on the senescence-associated inflammatory responses were studied via flow cytometry, cytochemical staining, Real time quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. Importantly, the treatment outcome of the n-HA with one single injection relative to the commercial HA product with four consecutive injections within one treatment course in an OA mouse model underwent anterior cruciate ligament transection (ACLT) was systematically evaluated. Our developed n-HA exhibited a perfect unification of high crosslink density, good injectability, excellent resistance to enzymatic hydrolysis, satisfactory biocompatibility, and anti-inflammatory responses through a series of in vitro studies. Compared to the commercial HA product with four consecutive injections, a single injection of n-HA contributed to equivalent treatment outcomes in an OA mouse model in terms of histological analysis, radiographic, immunohistological, and molecular analysis results. Furthermore, the amelioration effect of the n-HA on OA development was partially ascribed to the attenuation of chondrocyte senescence, thereby leading to inhibition of TLR-2 expression and then blockade of NF-κB activation. Collectively, the n-HA may be a promising therapeutic alternative to current commercial HA products for OA treatment.
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Food & Function
·
2023
·Vol. 14
·期 4
·1971-1988
·
IF 6.1
Ya-Li Wang,Song-Xia Lin,Yuan Wang,Tao Liang,Tao Jiang,Peng Liu,Xiao-Yi Li,Deng-Qin Lang,Qiang Liu,Chun-Yan Shen
Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.
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DESALINATION
·
2022
·
IF 11.211
Xiumin Zhang,Yongping Dong,Qingyi Wang,Hang Yu,Congjie Gao,Lixin Xue
Structures and NF performance of TFC-Co and TFC membranes activated with 50 % alcohol solutions were studied. Methanol and glycol solution activation increased water flux 2–4 times without trading off salt rejection while glycerin solution activation increased water flux 3–4 times with reduced salt rejection and increased dye/salt retention selectivity . The Stokes radius of TFC-Co membrane changed from 0.77 nm to 0.66, 0.78 and 0.92 nm while the TFC membrane changed from 0.54 nm to 0.55, 0.65 and 0.70 nm after activation with methanol, glycol and glycerin solutions, respectively. Capillary pore filling models were developed from pure alcohol absorption experiments including the stages of initial pore filling, pore expansion, pore relaxation and pore adjustment, while most Stokes radius after 50 % solutions activation were found to be close to the relaxed pore radius values (r rx ) or half of the expanded pore radius values (r ex ) from pure alcohol absorption experiments.
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Guanglu Wang,Jiajia Guo,Yeyun Ma,Yue Xin,Xiaomeng Ji,Ying Sun,Jian Zhang,Jingquan Dong
The increasing concern over environmental pollution caused by the pesticide avermectin used in aquaculture has attracted significant attention. The use of avermectin, a neurotoxic pesticide, in aquatic environments leads to toxic effects on non-target organisms, particularly causing harm to fish. The phenolic compound ferulic acid possesses excellent anti-inflammatory and antioxidant capabilities. This study was conducted by establishing a chronic exposure experiment to avermectin, proposes the use of ferulic acid as a dietary additive to protect the carp brain from damage caused by exposure to avermectin. Furthermore, it investigates the anti-inflammatory and antioxidant effects of ferulic acid in the carp brain under chronic exposure to avermectin. The experimental results demonstrate that ferulic acid can alleviate brain tissue inflammation and oxidative stress by modulating the Nrf2/Keap1 and NF-κB signaling pathways . It protects the carp brain from chronic avermectin-induced damage, preserves the integrity of the carp blood-brain barrier, enhances the levels of feeding factors, and thereby alleviates carp growth inhibition. These findings provide new therapeutic strategies and a theoretical foundation for the sustainable development of carp aquaculture.
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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2022
·
IF 10.319
Zhong Wang,Shuang Yuan,Tuo Zang,Tengxiao Li,Yudi Zhou,Jiaqi Liu,Tie Liu,Kai Wang,Qiang Wang
The noble metal Pt is an ideal catalyst for promoting the hydrogen evolution reaction (HER) during the electrolysis of water. However, Pt is also expensive and suffers from low utilization rates. In this work, a Pt-Ni 2 P/NF nanorod catalyst with a low Pt loading was synthesized under different magnetic fields, and it was found that the application of a magnetic field can increase the rate of the galvanic replacement reaction. When the magnetic field strength increases from 0 to 600 mT, the chemical reaction rate increases gradually, and the utilization rate of Pt increased by 2.3 times under 600 mT. The mechanism of the magnetic field-induced magnetohydrodynamic (MHD) effect on the galvanic replacement reaction was revealed. In a 1 M KOH solution and at a current density of 10 mA cm –2 , the overpotential of Pt-Ni 2 P/NF prepared by applying a 600 mT magnetic field was as low as 15 mV and the Tafel slope was 37 mV dec –1 , compared with values of 82 mV and 70 mV dec –1 for a specimen prepared without a magnetic field. Additionally, at an overpotential of 90 mV, the mass-based Pt activity of the former material was 12 times greater while its turnover frequency was 19 times greater. This work provides theoretical and technical knowledge expected to assist in the controllable preparation of materials in magnetic fields and the efficient utilization of metallic resources.
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Cell Communication and Signaling
·
2022
·Vol. 20
·期 1
·1-11
·
IF 7.525
Yang Jing,Tang Xujiao,Li Baiqiang,Shi Jinsong
In acute pancreatitis, activation of inflammatory signaling, including the nuclear factor-kappa B (NF-κB) pathway, within acinar cells is known to be an early intracellular event occurring in parallel with pathologic trypsinogen activation. Sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in endothelial inflammation, and our previous studies reported that S1PR2 deficiency significantly reduced the inflammatory response in liver injury under cholestasis conditions. However, the role of S1PR2 in inflammatory signaling activation within acinar cells and inflammatory responses during acute pancreatitis has not been elucidated. Here we report that S1PR2 was upregulated in the whole pancreas during acute pancreatitis. Blockade of S1PR2 by pharmacologic inhibition of S1PR2 by JTE-013 or AAV-mediated knockdown of S1PR2 improved the severity of pancreatic injury, as indicated by a significant reduction in inflammation and acinar cells death in acute pancreatitis mice. Moreover, S1PR2 is the predominant S1PRs expressed in pancreatic acinar cells and mediates NF-κB activation and the early inflammatory response within acinar cells under acute pancreatitis conditions via ROCK signaling pathways, not extracellular signal-regulated kinase pathways or p38 mitogen-activated protein kinase pathways. In addition, S1PR2 mediated macrophage NF-κB activation, migration and polarization toward the M1 phenotype. Therefore, these results demonstrated that the S1PR2-mediated early inflammatory response in acinar cells promotes the progression of acute pancreatitis, successfully linking local events to the systematic inflammatory response and leading to a novel therapeutic target for acute pancreatitis aimed at halting the progression of the inflammatory response.
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Shaoying Gong,Jiachen Zheng,Junjie Zhang,Yucong Wang,Zhixin Xie,Yubao Wang,Jianchun Han
Intestinal epithelial barrier dysfunction can cause several intestinal diseases. Flavonoids have been shown to be beneficial to the intestinal epithelial barrier function. However, the effects of taxifolin (TAX), a naturally occurring flavonoid, on the intestinal epithelial barrier function are unclear. Thus, the aims of this study were to investigate the protective effect and potential mechanism of TAX against lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction in a Caco-2 cell monolayer model. Our results showed that TAX increased the transepithelial electrical resistance (TEER) and decreased the fluorescein isothiocyanate (FITC)-dextran (4 kDa) flux in the damaged intestinal epithelial barrier. Meanwhile, TAX inhibited an LPS-induced decrease in mRNA and protein expression of tight junction (TJ) proteins (claudin-1, zonula occludens [ZO]-1, and occludin), and ameliorating the continuous distribution pattern disrupted of TJs. These results suggested that TAX ameliorated intestinal epithelial barrier dysfunction. Regarding the underlying mechanism, TAX reduced the LPS-induced secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in Caco-2 cell monolayers. In addition, TAX suppressed the phosphorylation of nuclear factor kappa-B (NF-κB), inhibitor protein of NF-κBα (IκBα), and myosin light chain (MLC), and downregulated the expression of myosin light chain kinase (MLCK) in LPS-treated Caco-2 cells. In summary, TAX can maintain TJ proteins by inhibiting the NF-κB/MLCK pathway and pro-inflammatory factor secretion to ameliorate LPS-induced intestinal epithelial barrier dysfunction. Thus, TAX is a promising candidate agent for use in functional food to ameliorate intestinal barrier dysfunction.
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