Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 37
·8634-8643
·
IF 5.344
Yongmei Li,Yuemei Li,Yandong Bai,Laixiang Lin,Yina Sun
Cerium oxide nanoparticles (NPs) due to their advanced catalytic performance have been widely used to treat oxidative damage. However, Ce2O3 NPs have not been further investigated in the treatment of acute oxidative injury in vivo. It is meaningful to improve the efficiency for treatment of acute oxidative injury with NPs in vivo. In this report, we designed Er3+-doped Ce2O3 (Er/Ce2O3) NPs with a size of 7.9 nm, which were used to treat acute liver injury. Er/Ce2O3 NPs realized high-efficiency catalysis of hydrogen peroxide (H2O2) at room temperature. An acute liver damage model was established through intraperitoneal injection of lipopolysaccharide (LPS) in C57 mice. By analyzing histopathological and biochemical indexes, Er/Ce2O3 NPs showed a significant improvement in LPS-induced acute liver injury. Acute liver oxidative damage can be treated within 24 hours, which proved the high catalytic efficiency of Er/Ce2O3 NPs in vivo. The activities of SOD, GPx and CTA increased and production of ROS decreased with Er/Ce2O3 NP treatment in comparison with LPS-induced injury, indicating that the mechanism of Er/Ce2O3 NPs in the treatment of acute oxidative damage of liver was mainly via catalysis of ROS products. Moreover, the protein expression levels of TNF-α, CD45 and IL-1β in liver decreased in the Er/Ce2O3 NPs-treated group, which indicated that Er/Ce2O3 NPs have the function of anti-inflammation property. Therefore, Er/Ce2O3 NPs can be applied to treat and prevent diseases caused by acute oxidative damage.
研究领域:
纳米技术
·
生物医学工程
·
药理学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2022
·Vol. 83
·期 8
·1758-1765
·
IF 5.004
Longxue Cai,Renqing Zeng,Qi Huang,Xianfa Liu,Zuohong Cao,Qicai Guo
Neuropathic pain affects millions of people in the worldwide, but the major therapeutics perform limited effectiveness. Paeonol (PAE) is widely distributed in Paeonis albiflora , and has manifested anti-inflammatory and antioxidative effects in multiple diseases. The present study aims to elucidate the effect of Paeonol (PAE) on neuropathic pain (NP) and the potential targets. Chronic constriction injury model was established to mimic NP in vivo in rats. The expression of GFAP, HDAC2, AHDAC3, Ac-H3K9, Histone-H3, Ac-H4K12, Histone-H4, TNF-α, IL-1β, and IL-6 was assessed by real-time polymerase chain reaction, western blot, and/or enzyme-linked immunosorbent assay kits. Ultimately, results indicated that intervention of PAE significantly blocked neuroinflammation and astrocytic activation via blocking HDAC/miR-15a signaling in CCI rats. These data revealed PAE is a novel therapeutic target for the treatment of neuropathic pain.
研究领域:
药理学
·
神经科学
·
疼痛管理
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2021
·
IF 3.352
Chen Yang,Pei Luo,Shi-jian Chen,Zhi-chao Deng,Xin-liang Fu,Dan-ning Xu,Yun-bo Tian,Yun-mao Huang,Wen-jun Liu
ABSTRACT Resveratrol, a natural antioxidant, anti-inflammatory plant extract, was found to have a protective effect in poultry subjected to heat stress. In this study, we strove to characterize resveratrol on intestinal of duck exposed to acute heat stress and investigate the underlying mechanism. A total of 120 Shan-ma ducks (60 days old) were randomly divided into 2 groups. The control group was fed a basal diet, and the resveratrol group was fed a basal diet supplemented with 400 mg/kg resveratrol. Animals in 2 groups were kept at a temperature of 24°C ± 2°C for 15 d. Then, animals of both groups were placed in an artificial climate room at 39°C. Twelve ducks of each group were sacrificed for sampling at 0, 30, and 60 min, respectively. Results indicated that resveratrol increased the ratio of villus height to crypt depth, increased the number of goblet cells, and reduced the histopathological damage of jejunum caused by acute heat stress. Furthermore, the gene expression of heat shock proteins ( HSP60, HSP70 , and HSP90 ) and tight junction proteins ( CLDN1 and OCLN ) was significantly increased in the resveratrol group compared to that in the control groups. Simultaneously, resveratrol significantly activated the SIRT1-NRF1/NRF2 signaling pathways, improved ATP level of jejunum, and increased SOD and CAT antioxidant enzymes activities. In addition, we found that the NF-κB / NLRP3 inflammasome signaling pathways were repressed under acute heat stress. Meanwhile, supplement resveratrol further inhibited the NLRP3 inflammasome pathway, decreased protein level of NLRP3 and caspase1 p20, reduced the secretion of IL-1β. Taken together, our results indicate that resveratrol against the oxidative damage and inflammation injury in duck jejunum induced by heat stress via active SIRT1 signaling pathways.
研究领域:
动物科学
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营养学
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生理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
·
2023
·
IF 3.8
He Xin,Wang Juan,Sun Lei,Ma Wenqi,Li Miao,Yu Shanshan,Zhou Qi,Jiang Jue
Mastitis is a disease involved in inflammation of breast which affects human and animals. Wogonin is one bioactive compound from many Chinese herbal medicines, which have multiple properties, including anti-inflammatory activity. However, the roles of wogonin in mastitis progression are largely undefined. Mastitis models were established using LPS-treated mice and mammary epithelial cells (MECs). Infiltration of inflammatory cells was analyzed by hematoxylin-eosin staining and myeloperoxidase (MPO) activity. Inflammatory cytokine (TNF-α and IL-1β) levels were detected via ELISA. The phosphorylation and total of Akt and NF-κB levels and content of Nrf2 and HO-1 were measured via western blot. Cell viability was examined by CCK-8 assay. Oxidative stress was assessed by ROS generation and levels of MDA, GSH, and SOD. Wogonin attenuated LPS-induced infiltration of inflammatory cells, increase of MPO activity and levels of TNF-α and IL-1β, and activation of the Akt/NF-κB pathway in murine mammary gland tissues, and promoted activation of Nrf2/HO-1 signaling. Wogonin did not affect MEC viability, but mitigated LPS-induced inflammation in MECs by reducing TNF-α and IL-1β levels. Wogonin relieved LPS-induced oxidative stress in MECs through decreasing ROS generation and MDA level and increasing GSH and SOD levels. Wogonin repressed LPS-induced activation of the Akt/NF-κB pathway in MECs and increased Nrf2/HO-1 signaling activation. Activated Akt/NF-κB signaling or Nrf2/HO-1 signaling inactivation reversed the suppressive effects of wogonin on LPS-induced inflammation and oxidative stress in MECs. Wogonin mitigates LPS-induced inflammation and oxidative stress of MECs via suppressing activation of the Akt/NF-κB signaling and activating Nrf2/HO-1 pathway, indicating the therapeutic potential of wogonin in mastitis.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
·
2023
·
IF 2.9
Fankai Gao,Rui Chen,Shuo Li,An Li,Bo Bai,Rulin Mi,Guofang Xue
Neuroinflammation plays a crucial role in the development of epilepsy, and suppressing neuroinflammation can delay epileptogenesis. Recent reports have demonstrated that (+)-borneol has neuroprotective effects in several brain disorders by reducing neuroinflammation. However, its effects on epilepsy have not been reported. In this research, we first studied the effect of different doses of (+)-borneol (3, 6, and 12 mg/kg) on neuroinflammation in a pilocarpine model of epileptogenesis by detecting IL-1β, TNF-α, and COX-2 expression. We demonstrated that different doses of (+)-borneol decreased IL-1β, TNF-α, and COX-2 levels, with 12 mg/kg having the most substantial effect. Furthermore, we examined the effects of 12 mg/kg (+)-borneol on neuronal damage, glial cell activation, and apoptosis in the hippocampus at different time points (1, 3, and 7 days) after SE . We found that (+)-borneol significantly ameliorated neuronal injury, decreased glial cell activation, and attenuated apoptosis. We also found that (+)-borneol inhibited the NF-κB pathway activation induced by SE. In conclusion, our results indicated that (+)-borneol reduces neuroinflammation by inhibiting the NF-κB pathway activation, exerts neuroprotective effects, and may have an inhibitory effect in epileptogenesis.
研究领域:
神经科学
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药理学
·
神经炎症
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癫痫
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2023
·Vol. 18
·期 5
·e0285613
·
IF 3.7
Nihal Hasan,Hongyi Yang
Background
Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis.
Methods
Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups.
Results
After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted.
Conclusion
Our results concluded that treatment duration and preparation methods affect the microbial therapies’ efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.
研究领域:
胃肠病学
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微生物学
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药理学
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免疫学
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Xiong Liping,Bao Han,Li Size,Gu Deao,Li Yuyang,Yin Qianwen,Li Wen,Miao Leiying,Liu Chao
Oxidative stress is closely linked to the etiology of temporomandibular joint osteoarthritis. (TMJ-OA) and is an important therapeutic target. Cerium oxide nanoparticles (CNPs) have been broadly studied owing to their powerful antioxidant properties and potential preventive and therapeutic effects against chronic diseases. The current study was designed to explore the protective effects of CNPs on the progression of TMJ-OA and their potential mechanisms. We detected the ability of CNPs to eliminate reactive oxygen species (ROS) in chondrocytes. Moreover, their protective effects on chondrocytes were detected in the level of gene and protein. Furthermore, TUNEL assay, histology and safranin O-fast green staining were used to detect the beneficial effects of CNPs on cartilage explants. The mechanism of CNPs, protecting condylar cartilage by reducing inflammation, was further explored by knocking down the Nuclear factor-erythroid 2-related factor (Nrf2) gene. CNPs could reduce the ROS levels in chondrocytes and cartilage explants and reverse the IL-1β-induced imbalance of cartilage matrix metabolism and apoptosis. The protective effects of CNPs on cartilage were lost after key antioxidant factors including Nrf2 and heme-oxygenase 1(HO-1) were significantly reduced. In conclusion, this study demonstrated for the first time that activating the Nrf2/HO-1 signaling pathway by CNPs might have therapeutic potential for TMJ-OA.
研究领域:
骨科
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纳米技术
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药理学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2014
·
IF 3.63
Demei Xu,Lihua Hu,Chuanyang Su,Xiaomin Xia,Pu Zhang,Juanli Fu,Wenchao Wang,Duo Xu,Hong Du,Qiuling Hu,Erqun Song,Yang Song
This study investigated the protective effects of curcumin on tetrachloro- p -benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS , COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling.
研究领域:
药理学
·
毒理学
·
肝病学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 23
·期 1
·1-10
·
IF 2.447
Tian Zhang,Tan Wang,Xinxu Chen,Zhenqiang Zhao,Zhibin Chen
The composition of the intestinal flora of patients with Parkinson's disease (PD) can change. However, whether reshaping the gut microbial composition can treat PD remains to be seen. The present study evaluated the effect of intestinal flora in the treatment of PD in a C57BL/6 mouse PD model induced by 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP). Chronic, low‑dose, MPTP‑treated mice exhibited upregulated gene expression levels of TNF‑α and IL‑1β in the substantia nigra (SN) of the mice, and induced intestinal microbial disorders. This indicated that the chronic low‑dose MPTP model could be used to evaluate the progress of early intestinal pathology and intestinal flora imbalance in PD. After transplantation of faecal bacteria to MPTP‑induced PD mice, the level of inflammation in the SN of the mice was reduced, and motor dysfunction was alleviated. Notably, faecal microbiota transplantation (FMT) upregulated the abundance of Blautia but downregulated Anaerostipes, Bifidobacterium, ASF356 and Ruminococcus in the gut of PD mice. In addition, FMT reduced the activation of microglia and astrocytes in the SN and reduced the expression levels of GSK3β, IL‑1β, inducible nitric oxide synthase and phosphorylated PTEN in the SN. Overall, the present study demonstrated that gut microbial dysfunction is associated with the pathogenesis of PD, and that FMT can protect PD mice by inhibiting neuroinflammation.
研究领域:
神经科学
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微生物学
·
神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 9
·1841-1851
·
IF 5.344
Qin Wang,Liming He,Donghao Fan,Wenlang Liang,Jiyu Fang
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints of the body. Although liposomes are a promising drug delivery vehicle, there is still a challenge of using conventional liposomes for the treatment of RA due to their short circulation time and physicochemical instability in blood vessels. Here, we report the formation of polymerized stealth liposomes composed of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-poly(ethyleneglycol) (DSPE-PEG2000) with a thin-film hydration method, in which DC8,9PC molecules are cross-linked in the bilayer of the liposomes by UV irradiation and the PEG chains present at the surface of the liposomes provide a stealth layer. We demonstrate that the polymerized stealth liposomes are stable and show long circulation time in blood vessels. They can be internalized by cells without significant toxicity. After being injected into arthritic rats, the polymerized stealth liposomes with loaded dexamethasone (Dex) show long blood circulation time and accumulate preferentially in inflamed joints, consequently suppressing the level of proinflammatory cytokines (TNF-α and IL-1β) in joint tissues, reducing the swelling of inflamed joints and alleviating the progression of RA. We believe that polymerized stealth liposomes can be used as a promising drug delivery vehicle for various therapeutic applications.
研究领域:
药理学
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药物递送系统
·
风湿病学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
·
2022
·
IF 5.702
Cai Yawen,Chai Yuhui,Fu Yu,Wang Yingdi,Zhang Yiming,Zhang Xue,Zhu Lingpeng,Miao Mingxing,Yan Tianhua
Amyloid β-protein (Aβ) is reported to activate NLRP3 inflammasomes and drive pyroptosis, which is subsequently involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). To date, the pathogenesis of AD is unfortunately insufficiently elucidated. Therefore, this study was conducted to explore whether Salidroside (Sal) treatment could benefit AD by improving pyroptosis. Firstly, two animal models of AD, induced, respectively, by Aβ1-42 and D-galactose (D-gal)/AlCl3, have been created to assist our appreciation of AD pathophysiology. We then confirmed that pyroptosis is related to the pathogenesis of AD, and Sal can slow the progression of AD by inhibiting pyroptosis. Subsequently, we established the D-gal and Nigericin-induced PC12 cells injury model in vitro to verify Sal blocks pyroptosis mainly by targeting the NLRP3 inflammasome. For in vivo studies, we observed that Aβ accumulation, Tau hyperphosphorylation, neurons of hippocampal damage, and cognitive dysfunction in AD mice, caused by bilateral injection of Aβ1-42 into the hippocampus and treatments with D-gal combine AlCl3. Besides, accumulated Aβ promotes NLRP3 inflammasome activation, which leads to the activation and release of a pro-inflammatory cytokine, interleukin-1 beta (IL-1β). Notably, both Aβ accumulation and hyperphosphorylation of Tau decreased and inhibited pyroptosis by downregulating the expression of IL-1β and IL-18, which can be attributed to the treatment of Sal. We further found that Sal can reverse the increased protein expression of TLR4, MyD88, NF-κB, P-NF-κB, NLRP3, ASC, cleaved Caspase-1, cleaved GSDMD, IL-1β, and IL-18 in vitro. The underlying mechanism may be through inhibiting TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway. Our study highlights the importance of NLRP3 inflammasome-mediated pyroptosis in AD, and how the administration of pharmacological doses of Sal can inhibit NLRP3 inflammasome-mediated pyroptosis and ameliorate AD. Thus, we conclude that NLRP3 inflammasome-mediated pyroptosis plays a significant role in AD and Sal could be a therapeutic drug for AD.
研究领域:
神经科学
·
药理学
·
分子生物学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2021
·
IF 5.293
Zhang Wei,Li Zhixing,Yang Haitao,Wang Guanglu,Liu Gang,Wang Yu,Bello Babatunde Kazeem,Zhao Panpan,Liang Wei,Dong Jingquan
Aeromonas sobria, a common conditional pathogenic bacteria, is widely distributed in the environment and causes gastroenteritis in humans or septicemia in fish. Of all Aeromonas species, A. sobria is the most frequently isolated from human infections especially in immunocompromised subjects. Innate immunity is the first protection system of organism to resist non-specific pathogens invasion; however, the immune response process of hosts against A. sobria infection re\mains unexplored. The present study established an A. sobria infection model using primary mouse peritoneal macrophages (PMφs). The adherence and cytotoxicity of A. sobria on PMφs were determined by May-Grünwald Giemsa staining and LDH release measurement. Pro-inflammatory cytokine expression levels were measured using qPCR, western blotting, and ELISA methods. We also investigated the levels of ASC oligomerization and determined the roles of active caspase-1 in IL-1β secretion through inhibition assays and explored the activated pattern recognition receptors through immunofluorescence. We further elucidated the roles of activated inflammasome in regulating the host’s inflammatory response through inhibition combined with ELISA assays. Our results showed that A. sobria induced lytic cell death and LDH release, whereas it had no adhesive properties on PMφs. A. sobria triggered various proinflammatory cytokine transcription level upregulation, and IL-1β occupied the highest levels. The pro-IL-1β protein expression levels increased in a dose-dependent manner with MOI ranging from 1 to 100. This process was regulated by ASC-dependent inflammasome, which cleavage pro-IL-1β into active IL-1β p17 with activated caspase-1 p20. Meanwhile, the expression levels of NLRP3 receptor significantly increased, location analysis revealed puncta-like surrounding nuclear, and inhibition of NLRP3 inflammasome downregulated caspase-1 activation and IL-1β secretion. Blocking of NLRP3 inflammasome activation through K+ efflux and cathepsin B or caspase approaches downregulated A. sobria–induced proinflammatory cytokine production. Overall, these data indicated that A. sobria induced proinflammatory cytokine production in PMφs through activating NLRP3 inflammasome signaling pathways.
研究领域:
免疫学
·
微生物学
·
细胞生物学
·
传染病学
✓ 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）