INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 23
·12844
·
IF 4.9
Zhining Gao,Haoyang Dai,Qinqin Zhang,Fan Yang,Chenxi Bu,Suiqing Chen
Acute liver injury (ALI) is an injury to liver tissue caused by viruses, drugs, alcohol, and oxygen deprivation, and is one of the most common and serious clinical disorders. Hydroxytyrosol (HT) is a naturally occurring polyphenolic compound isolated from forsythia and has excellent anti-inflammatory properties. However, the effect and mechanisms of HT in ALI remain unclear. We used the LPS/D-GalN induced experimental ALI mouse model and AML12 cells to reveal the efficacy and potential mechanisms of HT in ALI, and HE staining was used for the evaluation of pathologies. A biochemical assay was used to detect changes in liver function, RNA-seq was conducted to reveal the underlying mechanisms of HT for ALI, and WB, RT-qPCR, and IF were used to assess the effects of HT action. Furthermore, an in vitro ALI model against HT in AML12 cells induced by LPS/D-GalN was used to assess the HT protection mechanism. HT significant alleviated LPS/D-GalN-induced ALI in the mice by suppressing inflammatory. In terms of RNA-seq, HT improved the TNF, ECM-receptor interaction, and PI3K/AKT signaling pathway, and it downregulated the mRNA levels of VCAM-1, CXCL5, TNF-α and IL-6 in the liver. Mechanically, HT alleviated LPS/D-GalN in the mice by targeting TNF-α, thereby inhibiting the TNF-α/PI3K/AKT signaling pathway.
研究领域:
药理学
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肝病学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Qi Meng,Xiao Tan,Bi Wu,Siyan Zhang,Yuangang Zu,Shougang Jiang
The decoctions of sunflower ( Helianthus annuus L. HAL) stalk pith have been used to treat advanced cancer, and polysaccharide of sunflower stalk pith (HSPP) was key ingredient of the decoctions. To forage specially structured HSPP with anti-tumor effects and to uncover its mechanisms of anticancer activity, syngeneic mouse model of lung carcinoma metastasis was established and the HSPP was found to contain long-chain fatty acid. Encouragingly, the mean survival of the polysaccharide group (47.3 ± 12.8 d) and its sub-fractions group HSPP-4 (50.7 ± 13.0 d) was significantly increased compared with control group (38.7 ± 12.7 d) or positive control group (41.8 ± 13.4 d), ( n = 20, P < 0.01 vs. the control group or positive control group). Furthermore, the HSPP exerted inhibitory effects on the tumor cells' metastasis. Eventually, it is postulated that the polysaccharide could inhibit tumor proliferation and metastasis by reduction of TNF-α from the macrophage.
研究领域:
药理学
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肿瘤学
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植物化学
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DOI
PubMed
高影响因子
IEEE SENSORS JOURNAL
·
2024
·
IF 4.3
Hao-Yuan Cao,Dandan Wei,Yingying Hu,Bin Liu,Yue Fu,Juan Liu,Xing-Dao He,Jinhui Yuan,Wenbo Xiao,Qiang Wu
In this paper, a high sensitivity U-shape single mode- tapered four core-single mode (STFS) optical fiber biosensor is proposed and investigated for tumor necrosis factor-alpha (TNF-α) detection in both Phosphate Buffered Saline (1x) (PBS) and diluted serum. The surface of U-shape STFS biosensor is immobilized with TNF-α antibody (10 μg/mL), which will specifically bind with target TNF-α. The results demonstrate a Hill curve relationship between wavelength shift and TNF-α concentration (from 10
1
to 10
4
pg/mL diluted in PBS). The lowest concentration of TNF-α detected in the experiment is 10 pg/mL, with an average wavelength shift of 0.389 nm. The average wavelength fluctuation of the sensor in PBS is 0.099 nm, and the corresponding limit of detection (LOD) is 4.35 pg/mL. Results for the detection of TNF-α in blood sample is also presented. It is found that the deviation of detected TNF-α concentrations (13.00–15.03 pg/mL, calibrated by measured results in PBS) is -0.7%~14.7% compared to standard TNF-α concentration of 13.09 pg/mL in blood. This biosensor, with its simple structure and high sensitivity, has the potential to serve as a valuable reference in disease diagnosis and medical drug usage, offering promising application prospects.
研究领域:
生物医学工程
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光学传感
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分子诊断
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DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Guangtao Xu,Huan Gu,Bo Hu,Fei Tong,Daojun Liu,Xiaojun Yu,Yongxia Zheng,Jiang Gu
Brain ischemia/reperfusion (I/R) injury (BI/RI) is a leading cause of death and disability worldwide. However, the outcome of pharmacotherapy for BI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering neuronal activity in BI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of tumor necrosis factor (TNF)-α-loaded poly(ethylene glycol)-b-(poly(ethylenediamine L-glutamate)-g-poly(L-lysine)) (TNF-α/PEG-b-(PELG-g-PLL)) nanoparticles on BI/RI. The particle size of PEG-b-(PELG-g-PLL) and the loading and release rates of TNF-α were determined. The nanoparticle cytotoxicity was evaluated in vitro using rat cortical neurons. Sprague Dawley rats were preconditioned with free TNF-α or TNF-α/PEG-b-(PELG-g-PLL) polyplexes and then subjected to 2 hours ischemia and 22 hours reperfusion. Brain edema was assessed using the brain edema ratio, and the antioxidative activity was assessed by measuring the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content in the brain tissue. We further estimated the inflammatory activity and apoptosis level by determining the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-10, and nitric oxide (NO), as well as the expression of glial fibrillary acidic protein (GFAP), intercellular adhesion molecule-1 (ICAM-1), and cysteine aspartase-3 (caspase-3), in the brain tissue. We provide evidence that TNF-α preconditioning attenuated the oxidative stress injury, the inflammatory activity, and the apoptosis level in I/R-induced cerebral injury, while the application of block copolymer PEG-b-(PELG-g-PLL) as a potential TNF-α nanocarrier with sustained release significantly enhanced the bioavailability of TNF-α. We propose that the block copolymer PEG-b-(PELG-g-PLL) may function as a potent nanocarrier for augmenting BI/RI pharmacotherapy, with unprecedented clinical benefits. Further studies are needed to better clarify the underlying mechanisms.
研究领域:
药理学
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神经科学
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生物材料学
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DOI
PubMed
高影响因子
PULMONARY PHARMACOLOGY & THERAPEUTICS
·
2020
·
IF 2.681
Min Chen,Cuifen Chen,Yun Gao,Dongming Li,Dan Huang,Ziyu Chen,Xuanna Zhao,Qiu Huang,Dong Wu,Tianwen Lai,Guomei Su,Bin Wu,Beixian Zhou
Background Bergenin , a type of polyphenol compound, exhibits antiulcerogenic, anti-inflammatory, antitussive , and burn wound-healing properties. However, its therapeutic effect on tumor necrosis factor α (TNF-α)-induced proinflammatory responses in the airway and potential mechanisms of actions are still unclear. This study aimed to investigate the anti-inflammatory effects and mechanism of bergenin in TNF-α-stimulated human bronchial epithelial (16-HBE) cells. Methods Cell Counting Kit-8 was used to evaluate cytotoxicity. Cytokine expression was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay. Immunofluorescence, western blot , and sirtuin-1 (SIRT1) activity assays were employed to investigate potential molecular mechanisms. Results Bergenin obviously decreased both mRNA and protein expression levels of interleukins 6 and 8 (IL-6 and IL-8) in TNF-α-stimulated 16-HBE cells. Bergenin blocked TNF-α-mediated activation of nuclear factor κB (NF-κB) signaling and NF-κB nuclear translocation. Interestingly, RT-qPCR and western blotting results revealed that bergenin did not affect SIRT1 expression, but significantly increased its activity. Bergenin-mediated SIRT1 activation was further confirmed by results indicating decreased acetylation levels of NF-κB-p65 and p53. Moreover, the inhibitory effects of bergenin on mRNA and protein expression levels of IL-6 and IL-8 were reversed by a SIRT1 inhibitor. In addition, combining bergenin and dexamethasone (DEX) yielded additive effects on the reduction of IL-6 and IL-8 expression. Conclusions These findings demonstrate that bergenin could suppress TNF-α-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-κB signaling pathway , which may provide beneficial effects for the treatment of airway inflammation associated with asthma.
研究领域:
药理学
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免疫学
·
细胞生物学
·
呼吸医学
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DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2021
·
IF 3.228
Jianqing Chen,Bing Shao,Jinliang Wang,Zhiqiang Shen,Honggui Liu,Shu Li
Chlorpyrifos (CPF) is an organophosphate insecticide and can cause cell death of animals. In the study, the common carp were exposed to CPF at 0 μg/L (the control group), 1.16 μg/L (the low dose group), 11.6 μg/L (the medium dose group), and 116 μg/L (the high dose group), respectively. The carp were euthanized at the 30th day and gills were collected immediately. The ultrastructural and histopathological observations showed obvious necrosis characteristics and inflammatory injury in the CPF-treated groups. CPF exposure activated the MAPK pathway, in which the mRNA and protein expressions of extracellular signal-regulated (ERK), p38 MAP kinase (p38), and c-Jun N-terminal kinase (JNK) were increased; the mRNAs and proteins of NF-κB and TNF-α were activated; and the mRNAs and proteins of necroptosis related genes were changed (the mRNA and protein expression of RIPK1 , RIPK3 , MLKL, and FADD were increased and caspase-8 was decreased) with concentration dependency. Taken together, we concluded that CPF exposure activated the MAPK/NF-κB/TNF-α pathway, promoted inflammatory injure and evoked necroptosis in common carp gills. In addition, CPF-induced inflammation and necroptosis was concentration dependency. The toxic effects of CPF on gills provided data for both aquaculture and toxicological studies.
研究领域:
环境毒理学
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鱼类生理学
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分子生物学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 23
·期 4
·1-9
·
IF 2.751
Min Yi,Guanglei Wang,Jianhua Niu,Minghui Peng,Yi Liu
Periodontitis is a common chronic inflammatory oral disease. The objective of periodontal treatment is to control infection whilst regenerating damaged periodontal tissue. The present study aimed to determine the potential effects of pterostilbene (PTE), a representative stilbene compound, on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). Different concentrations (1, 5, 10 and 20 µM) of PTE were applied to hPDLSCs, after which Cell Counting Kit‑8 and western blotting assays were performed to examine the protein levels of Ki67, PCNA, p‑IκBα, IκBα, Bcl‑2, Bax, cleaved caspase3. The effect of PTE on the release of inflammatory factors, including IL‑1β, IL‑6 and IL‑10 was assessed by RT‑qPCR. The apoptosis of TNF‑α‑induced hPDLSCs was evaluated by TUNEL assay and western blotting. Additionally, the role of PTE in hPDLSC mineralization was evaluated using alizarin red staining. The expression levels of mineralization indices, including RUNX2 and ALP were subsequently determined using western blotting. Subsequently, the target of PTE was predicted using TargetNet database and AutoDock v4.2 software and verified using western blotting. The results of the present study revealed that PTE promoted the proliferation of hPDLSCs in a concentration‑dependent manner. Furthermore, PTE treatment decreased the release of inflammatory factors and alleviated the apoptosis of TNF‑α‑induced hPDLSCs. PTE was also demonstrated to promote the formation of mineral nodules in TNF‑α‑induced hPDLSCs. The Targetnet database, along with molecular docking, indicated that histone deacetylases (HDACs) were the probable targets of PTE upstream of regulating periodontitis. The results of western blotting implied that TNF‑α significantly increased expression levels of HDAC2, 4, 6 and 8, whilst PTE treatment markedly decreased HDAC4, 6 and 8 expression in a concentration‑dependent manner compared with the TNF‑α group, which further confirmed these conclusions. In summary, results of the present study revealed that PTE promoted TNF‑α‑induced hPDLSC proliferation and differentiation, whilst alleviating inflammation and apoptosis. PTE also inhibited the expression of HDACs, which may be involved in the mechanism of periodontitis.
研究领域:
牙科学
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药理学
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细胞生物学
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炎症性疾病
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 24
·期 1
·320
·
IF 6.208
Xiaoyu Zhang,Yuan Gao,Zhuangzhuang Liu,Wenjing Li,Yuan Kang,Ximeng Li,Zhenlu Xu,Cheng Peng,Yun Qi
As a worldwide health issue, obesity is associated with the infiltration of monocytes/macrophages into the adipose tissue causing unresolved inflammation. Monocyte chemoattractant protein-1 (MCP-1) exerts a crucial effect on obesity-related monocytes/macrophages infiltration. Clinically, aspirin and salsalate are beneficial for the treatment of metabolic diseases in which adipose tissue inflammation plays an essential role. Herein, we investigated the effect and precise mechanism of their active metabolite salicylate on TNF-α-elevated MCP-1 in adipocytes. The results indicated that salicylate sodium (SAS) could lower the level of MCP-1 in TNF-α-stimulated adipocytes, which resulted from a previously unrecognized target phosphodiesterase (PDE), 3B (PDE3B), rather than its known targets IKKβ and AMPK. The SAS directly bound to the PDE3B to inactivate it, thus elevating the intracellular cAMP level and activating PKA. Subsequently, the expression of MKP-1 was increased, which led to the decrease in p-EKR and p-p38. Both PDE3B silencing and the pharmacological inhibition of cAMP/PKA compromised the suppressive effect of SAS on MCP-1. In addition to PDE3B, the PDE3A and PDE4B activity was also inhibited by SAS. Our findings identify a previously unrecognized pathway through which SAS is capable of attenuating the inflammation of adipocytes.Keywords:cAMP;MKP-1;p-ERK;p-p38;metaflammation
研究领域:
药理学
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免疫学
·
代谢
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Cuihua Zhang,Yawen Yao,Wenqiu Xu,Jieying Zhou,Hua Yu,Ying Li,Wei Xiong
Efficient cytosolic delivery of small interfering RNA (siRNA) remains a challenge in RNA therapeutics, particularly for oral administration. Identifying new cytosolic stimulus-responsive targets is thus crucial for optimizing siRNA delivery. Given the elevated intracellular arginase-1 (Arg1) levels in inflamed colonic mucosa, we developed lipid nanoparticles (siRNA-LANPs) derived from L-arginine-modified chitosan (ACS) for the cytosolic release of TNF-α-siRNA to treat ulcerative colitis (UC). The siRNA-LANPs exhibited superior Arg1-binding affinity compared to its substrate, L-arginine, enabling rapid Arg1-responsive release. Moreover, we found that siRNA-LANPs maintained nanoparticle stability, and 84.5 % of the loaded siRNA remained intact in simulated digestive fluids over 12 h. Following oral administration, siRNA-LANPs efficiently penetrated the mucus layer and preferentially accumulated in inflamed colonic tissue compared to healthy colon tissue. In DSS-induced colitis mice, siRNA-LANPs significantly reduced disease severity through TNF-α silencing, achieving greater therapeutic efficacy than sulfasalazine (a first-line UC treatment). The siRNA-LANPs exhibited superior TNF-α silencing compared to transfection reagent Lipo3000 and TNF-α biologic agent infliximab. The enhanced performance was attributed to multiple endocytic pathways, improved lysosomal escape capability (29.7 %), and Arg1-mediated cytoplasmic siRNA release. In summary, Arg1 seems to be a promising intracellular target for stimulus-responsive, oral siRNA delivery in UC treatment.
研究领域:
RNA治疗
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纳米医学
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胃肠病学
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药物递送
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分子生物学
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Yishu Liu,Jingsong Liu,Yangyang Wang,Yubo Zhang,Zhibin Peng,Pengfei Li,Mi Li,Bing Xue,Yansong Wang
Introduction: Spinal cord injury (SCI) is a severe neurological condition with limited treatment options. Polylactic acid (PLA)+graphene oxide (GO)+anti-TNF-α (Ab) composites have shown potential in regulating immune responses and promoting neural repair.Methods: Electrospinning PLA+GO+Ab materials were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and X-ray diffraction (XRD). Their effects on neural stem cells (NSCs) and macrophage polarization were evaluated through in vitro assays, including proliferation, migration, differentiation, and flow cytometry. A rat SCI model was used to assess motor function recovery and histological changes.Results: PLA+GO+Ab promoted NSC proliferation, migration, and differentiation while inducing macrophage polarization toward the M2 phenotype, reducing inflammation. In the SCI model, PLA+GO+Ab treatment enhanced motor function recovery, reduced spinal cord damage, and promoted axonal regeneration and oligodendrocyte maturation. RNA sequencing identified activation of the Rap1 signaling pathway, contributing to these effects.Discussion: PLA+GO+Ab composites effectively modulate the neuroimmune microenvironment, supporting SCI recovery by promoting neural repair and immune regulation. These findings suggest its potential as a therapeutic biomaterial for SCI treatment.
研究领域:
生物医学工程
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神经科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2018
·Vol. 11
·期 5
·2872-2884
·
IF 7.994
Iqbal Shoaib,Du Xiaojiao,Wang Jilong,Li Hongjun,Yuan Youyong,Wang Jun
Nanoparticle (NP) drug delivery systems have been successfully designed and implemented to orally deliver siRNAs for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG 5K - b -PLGA 10K ) NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs (ANPs), plain NPs (PNPs), or carboxylated NPs (CNPs) based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-α secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis (UC). This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.
研究领域:
药学科学
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纳米技术
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炎症性疾病
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药物递送系统
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产品关联
DOI
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 47
·20170-20185
·
IF 7.79
Yanqin Song,Muhammad Ismail,Qi Shan,Jianing Zhao,Yanping Zhu,Leiming Zhang,Yuan Du,Longbing Ling
Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder that has seriously affected human health worldwide and its current management requires more successful therapeutic approaches. The combination of nanomedicines and pathophysiology into one system may provide an alternative strategy for precise RA treatment. In this work, a practical ROS-mediated liposome, abbreviated as Dex@FA-ROS-Lips that comprised synthetic dimeric thioether lipids (di-S-PC) and a surface functionalized with folic acid (FA), was proposed for dexamethasone (Dex) delivery. Incorporation with thioether lipids and a FA segment significantly improved the triggered release and improved the triggered release of cytotoxic Dex as well as the active targeting of RA, altering its overall pharmacokinetics and safety profiles in vivo. As proof, the designed Dex@FA-ROS-Lips demonstrated effective internalization by LPS-activated Raw264.7 macrophages with FA receptor overexpression and released Dex at the inflammatory site due to the ROS-triggered disassembly. Intravenous injection of this Dex@FA-ROS-Lips into adjuvant-induced arthritis (AIA) mice led to its incremental accumulation in inflamed joint tissues and significantly alleviated the cartilage destruction and joint swelling via suppression of proinflammatory cytokines (iRhom2, TNF-α and BAFF), as compared to the effect of commercial free Dex. Importantly, the Dex@FA-ROS-Lips nanoformulation showed better hemocompatibility with less adverse effects on the body weight and immune organ index of AIA mice. The anti-inflammatory mechanism of Dex@FA-ROS-Lips was further studied and it was found that it is possibly associated with the down-regulation of iRhom2 and the activation of the TNF-α/BAFF signaling pathway. Therefore, the integration of nanomedicines and the RA microenvironment using multifunctional Dex@FA-ROS-Lips shall be a novel RA treatment modality with full clinical potential, and based on the enhanced therapeutic effect, the signaling pathway of iRhom2/TNF-α/BAFF reasonably explained the mechanism of Dex@FA-ROS-Lips in anti-RA, which suggested a molecular target for RA therapy and other inflammatory diseases.
研究领域:
药理学
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纳米技术
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免疫学
·
风湿病学
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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）