Biomolecules & Therapeutics
·
2020
·
IF 3.47
Zhenling Zhang,Qiuping Zhang,Fang Li,Yi Xin,Zhijun Duan
The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl 4 ) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl 4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.
研究领域:
胃肠病学
·
细胞生物学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Zhihui Rao,Mengyan Cao,Zehui Chen,Xiujian Zhao,Xiao Gong
Ho-based lead-free double perovskite microcrystals (MCs), Cs 2 NaHo 1-x Yb x Cl 6 , are synthesized and demonstrated to be promising optical temperature sensing materials by understanding the concentration-dependent upconversion (UC) luminescence mechanisms. By optimizing the dopant concentration, a dominant emission shifting from red to green is successfully achieved in an activator-rich system. During this process, the red to green emission intensity ratio (R/G) can be changed from 12.5 (pure red light) to 0.14 (pure green light). It is clarified that the cross-relaxation (CR) process between activator and the energy transfer process between Yb 3+ and Ho 3+ are the key mechanisms of UC luminescence intensity and R/G ratio variation. Moreover, the intensity of red and green UC emission shows strong dependence on temperature, resulting from the competition between CR and energy transfer in the emission levels. The high-sensitivity Ho-based thermometer can be obtained by Cs 2 NaHo 0.99 Yb 0.01 Cl 6 MCs with bright red UC luminescence, whose fluorescence intensity ratio thermometer gains maximum relative sensitivities reaching 0.68% K −1 at 400 K. The multicolor UC luminescence quantitative modeling mentioned here is crucial for understanding the concentration-dependence UC luminescence characteristics and to optimize the design of the Ho-based thermometer. This study can be an extension of the application range for perovskite UC materials.
研究领域:
材料科学
·
光学工程
✓ 已验证
产品关联
DOI
高影响因子
Journal of Neuroinflammation
·
2020
·Vol. 17
·期 1
·1-13
·
IF 5.793
Bian Hetao,Wang Gaohua,Huang Junjie,Liang Liang,Zheng Yage,Wei Yanyan,Wang Hui,Xiao Ling,Wang Huiling
Background Recently, depression has been identified as a prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the preventive effect and potential mechanism of DHLA in the lipopolysaccharide (LPS)-induced sickness behavior in rats. Methods Adult male Sprague–Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine (Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally 1 h before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins. Results The DHLA and fluoxetine treatment exerted preventive effects in LPS-induced sickness behavior rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1β in LPS-induced sickness behavior rats. PD98059 abolished the effects of DHLA on preventive effect as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the preventive effect of DHLA administration via the decreased expression of HO-1. Conclusions These findings suggested that DHLA exerted a preventive effect via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced sickness behavior rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.
研究领域:
神经科学
·
药理学
·
分子生物学
·
精神病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
·
2025
·Vol. 37
·期 1
·14
·
IF 2.8
Li Yonghang,Su Fuyan,Cai Qingfeng,Guo Hui,Chai Xiaona,Zou Hua
Yb and Re (Re = Er, Ho) codoped Sr₂ScSbO₆ double perovskite phosphors were synthesized via high-temperature solid-state reaction. Under excitation by a 980 nm laser, the Yb 3 ⁺/Er 3 ⁺ codoped sample exhibits weak green emissions at 522 and 558 nm, along with a dominant red emission at 660 nm, which is attributed to efficient cross-relaxation processes that enhance population of the 4 F 9/2 level. Notably, the emission intensities are temperature-dependent, resulting in distinct and visible changes in emission color with increasing temperature. Temperature sensing based on the fluorescence intensity ratio (FIR) demonstrates a maximum relative sensitivity of 0.73% K⁻ 1 at 490 K and an absolute sensitivity of 1.43% K⁻ 1 at 730 K. In contrast, the Yb 3 ⁺/Ho 3 ⁺ codoped sample exhibits dual green (543 nm) and red (661 nm) emissions, along with superior performance in high temperatures, achieving a relative sensitivity of 0.59%·K⁻ 1 and an absolute sensitivity of 0.42%·K⁻ 1 at 670 K. These results suggest that the Yb 3 ⁺/Er 3 ⁺ system is more suitable for low-to-intermediate temperature sensing, while the Yb 3 ⁺/Ho 3 ⁺ system is better suited for high-temperature optical thermometry applications.
研究领域:
材料科学
·
无机化学
·
功能材料
·
光学材料
·
传感器技术
·
固体物理
✓ 已验证
产品关联
DOI
高影响因子
INFLAMMATION RESEARCH
·
2025
·Vol. 74
·期 1
·1-19
·
IF 5.4
Weng Xiuhong,Wang Simin,Wang Qing,Wei Mingbo,Cheng Bo
Background Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by xerostomia and autoimmune sialadenitis. Interferon-γ (IFN-γ) induces ferroptosis in salivary gland epithelial cells (SGECs), leading to salivary gland (SG) hypofunction. We previously demonstrated the beneficial effects of melatonin (MLT) in alleviating SG dysfunction and inflammation in a pSS animal model. However, the precise underlying mechanism remains unclear. Methods Female NOD/ltj and ICR mice were used as the pSS mouse model and control group, respectively. MLT was administered via intraperitoneal injection to NOD/ltj mice to detect its effect on ferroptosis in SGs. Primary human SGECs and A253 cells were treated with IFN-γand ferroptosis inducers, with or without MLT. Results Exogenous MLT alleviated pathological SG alterations and promoted saliva production through inhibiting SGEC ferroptosis. MLT inhibited SGEC ferroptosis induced by IFN-γ and ferroptosis inducers via nuclear factor erythroid 2-related factor 2/heme oxygenase-1/glutathione peroxidase 4 (NRF2/HO-1/GPX4) pathway activation. Moreover, MLT suppressed the nuclear factor-kappa B (NF-κB) pathway, which is triggered by ferroptosis in SGECs. Nevertheless, ML385-mediated NRF2 inhibition abrogated the antiferroptotic protective effects of MLT on SGECs. Conclusions MLT inhibits SGEC ferroptosis through NRF2/HO-1/GPX4 pathway activation and thus attenuates ferroptosis-triggered NF-κB activity. Melatonin represents a potential therapeutic approach for pSS owing to its capacity to regulate ferroptosis.
研究领域:
免疫学
·
细胞生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 1
·215
·
IF 3.098
Xinyan Peng,Chongshan Dai,Quanwen Liu,Junke Li,Jingru Qiu
This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl4)-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl4exposure. At 24 h, curcumin-attenuated CCl4induced elevated serum transaminase activities and histopathological damage in the mouse’s liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl4-induced oxidative stress, characterized by decreased malondialdehyde (MDA) formations, and increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) content, followed by a decrease in caspase-9 and -3 activities. Curcumin pre-treatment significantly decreased CCl4-induced inflammation. Furthermore, curcumin pre-treatment significantly down-regulated the expression of TGF-β1 and Smad3 mRNAs (bothp< 0.01), and up-regulated the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (bothp< 0.01) in the liver. Inhibition of HO-1 attenuated the protective effect of curcumin on CCl4-induced acute liver injury. Given these outcomes, curcumin could protect against CCl4-induced acute liver injury by inhibiting oxidative stress and inflammation, which may partly involve the activation of Nrf2/HO-1 and inhibition of TGF-β1/Smad3 pathways.Keywords:curcumin;acute liver injury;Nrf2/HO-1 pathway;oxidative stress;TGF-β1/Smad3 pathway
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Yulong Li,Shu Wang,Rui Feng
Cadmium (Cd) is a non-essential heavy metal that is highly toxic to testicle. Selenium (Se) is known to possess antagonistic effects against Cd toxicity, yet the precise mechanisms through which Se counteracts Cd-induced testicular damage in chickens through Nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway, oxidative stress (OS), apoptosis, and inflammation remained unclear. In the present study, the experimental model of chicken testis was established by incorporating CdCl 2 and Na 2 SeO 3 into the dietary intake. After 60 days, chickens from each group were euthanized, and testicular and serum samples were subsequently collected. Ultrastructural assessment revealed that Se supplementation significantly mitigated the testicular damage induced by Cd. Se effectively suppressed the Cd-induced elevation in ROS, MDA, and H 2 O 2 levels, while also preventing the downregulation of CAT, GSH, and T-AOC levels. Furthermore, Se administration ameliorated the reduction in the expression levels of Nrf2, HO-1, and Bcl-2 induced by Cd, and counteracted the overexpression of Caspase-3, Bax, Cyt-c, and Caspase-9, TNF-α, IL-2, IL-6, and IL-1β. Meanwhile, immunofluorescence data demonstrated that Se attenuated the Cd-induced decrease in Nrf2 and HO-1 expression and the upregulation of IL-6 expression. In conclusion, this study elucidated that Se might mitigate Cd-induced oxidative stress in chicken testicles through the stimulation of the Nrf2/HO-1 signaling pathway, thereby inhibiting apoptosis and inflammation, and was beneficial in reducing Cd-induced testicular injury.
研究领域:
毒理学
·
生殖生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2017
·
IF 3.546
Yong Yang,Zhiyu Xi,Yuan Xue,Jie Ren,Yuhao Sun,Baofeng Wang,Zhihong Zhong,Guo-yuan Yang,Qingfang Sun,Liuguan Bian
Oxidative stress mediated secondary injury contributes to neurological deterioration after intracerebral hemorrhage (ICH). Astrocytes, the most dominant cells in the central nervous system (CNS), play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemoglobin (Hb), the primary component released by hemolysis, is an effective activator of astrocytes. Hemin, the product of Hb degradation, is highly toxic due to the induction of reactive oxygen species (ROS). We speculate that Hb-activated astrocytes are resistant to hemin-induced toxicity. To verify our speculation, Hb-pretreated astrocytes were exposed to hemin, intracellular ROS accumulation and cell apoptosis were evaluated. Heme oxygenase 1 (HO-1) and nuclear transcription factor-erythroid 2 related factor (Nrf2) expression were observed to explore the potential mechanism. The results demonstrated that Hb induced upregulation and nuclear translocation of Nrf2 in astrocytes, resulted in HO-1 upregulation, which contributed to reduced ROS accumulation and apoptosis rate . Knocking down Nrf2 expression by siRNA suppressed Hb-induced upregulation of HO-1 expression and increased the susceptibility of Hb-pretreated astrocytes to hemin-induced toxicity. Taken together, Hb-activated astrocytes acquired resistance to hemin-induced toxicity via Nrf2/HO-1 pathway. This phenomenon can be considered as the adaptive self-defense in the pathological process of ICH. Hb pre-warned astrocytes and enhanced their capability of handling the coming hemin “flood”. Nrf2/HO-1 may be employed as a target for neuroprotection after ICH.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Lili Huang,Yinqi Chen,Hua Zhou,Huihui Chen,Xiping Wu,Zhuochao Wu,Zhoudi Liu,Zhiwei Zheng
Background: Cerebral ischemia-reperfusion injury (CIRI) is a secondary brain injury that occurs after thrombolysis and is a primary cause of death in ischemic stroke patients. Antioxidants that effectively reduce oxidative stress are an efficient treatment approach for CIRI. Here, a novel diimide compound was synthesized using the chemical structure of previously designed anti-inflammatory skeletons.Methods and results: The antioxidant activities of five compounds (Z1–Z5) were preliminarily evaluated using the hydrogen peroxide-induced PC12 cell damage model, of which Z3 exhibited the best antioxidant effect, even exceeding that of the positive control (tert-butylhydroquinone). Enrichment analysis using network targeting and network pharmacology methods predicted seven candidate core target genes of Z3 in CIRI. Of these targets, computer molecular docking analysis predicted that Z3 has the strongest binding affinity for nuclear factor erythroid 2-related factor (Nrf2). MTT and colony formation assays, reactive oxygen species analysis, immunofluorescence, and immunoblotting experiments verified that Z3 reduced reactive oxygen species to play a protective antioxidant role via the Nrf2/hemoxygenase 1 (HO-1) pathway. The protective effect of Z3 in vivo was explored through TTC staining and neurobehavioral scoring of CIRI model mice.Conclusion: This study provides a new drug development strategy and candidate drug for the treatment of CIRI, offering ideas for the design of new antioxidants.
研究领域:
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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.
研究领域:
药理学
·
免疫学
·
皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2017
·Vol. 53
·期 5
·3267-3279
·
IF 2.599
Duan Haojie,Wang Yifang,Li Shuo,Li Haiying,Liu Li,Du Liting,Cheng Yali
Pure and Ho-doped In 2 O 3 nanotubes (NTs) and porous nanotubes (PNTs) were successfully synthesized by conventional electrospinning process and the following calcination at different temperatures. X-ray diffractometry (XRD), thermogravimetric analysis (TGA), Raman spectrometer, energy-dispersive spectroscopy, scanning and transmission electron microscopy were carefully used to investigate the morphologies, structures and chemical compositions of these samples. Their sensing properties toward ethanol gas were studied. Compared with pure In 2 O 3 NTs (response value is 17), pure In 2 O 3 PNTs (response value is 20) demonstrated enhanced sensing characteristics. What’s more, the response of Ho-doped In 2 O 3 PNTs sensors to 100 ppm ethanol was up to 60 at 240 °C, which increased three times more than that of the pure In 2 O 3 PNTs. Additionally, the minimum concentration for ethanol was 200 ppb (response value is 2). The increased gas-sensing ability was attributed not only to the hollow and porous structure, but to the Ho dopant. Furthermore, Ho-doped In 2 O 3 PNTs enable sensor to discriminate between ethanol and the other gas distinctly, particularly acetone that is usually indistinguishable from ethanol. Also, by analyzing XRD, TGA and Raman spectrometer, a possible formation mechanism of porous nanotubes and sensing mechanism were put forward.
研究领域:
材料科学
·
纳米技术
·
传感器学
·
无机功能材料
·
化学传感
✓ 已验证
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2016
·
IF 3.584
Chongshan Dai,Bin Li,Yan Zhou,Daowen Li,Shen Zhang,Hui Li,Xilong Xiao,Shusheng Tang
The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress , mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor –kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX , a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.
研究领域:
药理学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）