Experimental and Therapeutic Medicine
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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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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
Scientific Reports
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2025
·Vol. 15
·期 1
·1-11
·
IF 3.9
Li Wenlan,Zhang Zijie,Jiang Zixiao,Barasarathi Jayanthi,Zhou Ying,Liu Sui,Lee Shiou Yih,Liu Yangyang
Psychotria rubra Herbal Tea (PRHT) is a traditional Chinese folk medicine used to treat in-flammation induced by respiratory infections. Its specific mechanisms of action, however, remain unclear. The study combined ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and in vitro cell experiments to systematically analyze the chemical composition and validate the biological activity of PRHT. Protein-protein interaction (PPI) network analysis and molecular docking were used to identify key targets and mechanisms. PRHT was found to contain 128 active compounds, including alkaloids, amino acids and their derivatives, and flavonoids. Key targets such as STAT3, IL-6, and TP53 were identified through PPI network analysis. PRHT exhibited significant anti-inflammatory effects by modulating the STAT3/IL-6/TNF-α signaling pathway. Experimental results demonstrated that PRHT inhibited the release of inflammatory cytokines in a dose-dependent manner. Molecular docking confirmed strong interactions between PRHT components and core targets. The study reveals that PRHT exerts anti-inflammatory effects by regulating the STAT3/IL-6/TNF-α signaling pathway, contributing to inflammation balance and tis-sue repair. These findings provide scientific evidence for the development of PRHT as a functional anti-inflammatory agent and offer new insights into treatment strategies for respiratory infections.
研究领域:
中药学
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分子生物学
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网络药理学
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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
BIOMEDICAL MICRODEVICES
·
2017
·Vol. 19
·期 3
·1-8
·
IF 2.062
Li Yuan,Lu Yao,Chen Qiong,Kang Yuejun,Yu Ling
Retinopathy is a complication of diabetes that affects the eyes; it stems from damage to the microvasculature of the retina and eventually compromises vision. The diagnosis of retinopathy is difficult to make because there are no early symptoms or warning signs. Dysfunction of the retina’s microvascular networks is believed to be associated with inflammatory cytokines and tumor necrosis factor alpha (TNF-α). To investigate the effect of these cytokines, such as TNF-α, a polydimethylsiloxane (PDMS)/glass hydride microfluidic device reflecting the physiological structure of the retina’s microvasculature was developed. In this model, the bifurcations and tortuosity of branch vessels were based on photographs of the fundus and an endothelial cell layer (EA.hy926 cells) were reconstructed within the microfluidic network. The adhesion, spreading, and growth of cells was ensured by optimizing the conditions for cell seeding and perfusion. Fluorescent staining was used to visualize the cytoskeleton and measurement of the nitric oxide (NO) level proved that the endothelial EA.hy926 cells had spread in the direction of flow perfusion system, forming artificial vascular networks. The endothelial layer was further challenged by TNF-α perfusion. Cytokine treatment increased the anchoring of peripheral blood mononuclear cells (PBMCs) on the endothelial layer. The microfluidic device developed in this study provides a low-cost platform reflecting the physiological structures of the retina’s microvasculature. It is anticipated that this device will be useful in evaluating the diseased retina as well as in drug screening.
研究领域:
医学
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生物工程
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DOI
PubMed
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
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Ting Liu,Qiang Meng,Yijun Zhang,Mengxi Yu,Jianming Ye,Wei Song,Yane Luo,Tianli Yue
The gut microbiota and its associated micro-ecosystem were closely related to the onset and development of ulcerative colitis (UC). We found that Corynebacterium glutamicum (C. glutamicum) helps rebuild gut eubiosis from diabetes dysbiosis, while its effects on UC remain unknown. This study aims to investigate the therapeutic effects and mechanisms of C. glutamicum on UC. In this study, C. glutamicum was encapsulated with thiolated hyaluronic acid (HA-SH) to form a hydrogel termed as CG-HA-SH. The adhesion and distribution of CG-HA-SH in the intestine were evaluated, along with its therapeutic effects on UC mice, including its impact on the gut microbiota. Additionally, changes in short-chain fatty acids (SCFAs) in the intestines of UC mice were analyzed, and RNA sequencing (RNA-Seq) was employed to investigate the mechanisms by which C. glutamicum alleviated inflammation. HA-SH enhanced the resistance of C. glutamicum in gastric and intestinal fluids, providing approximately 12 hours of adhesion at colitis inflammation sites. C. glutamicum reduced the levels of pro-inflammatory factors like IL-1β (by 97.31%) and TNF-α (by 90.10%) while increasing anti-inflammatory IL-10 (by 197.59%) in the colon. It also increased the abundance of E. fissicatena, Muribaculum, and butyrate, enhanced intestinal tight junctions (OCC, by 318.93%) and mucus barrier (MUC2, by 515.93%). The mRNA levels of cIAP1/2 decreased by 4.33 folds, their protein expression levels were reduced by 36.97% correspondingly. The enrichment of TNF pathway was the most significant. Therefore, C. glutamicum exhibited remarkable efficacy in alleviating inflammation and reshaping dysbiotic gut microbiota by downregulating the cIAP1/2-mediated TNF signaling pathway and NF-κB signaling pathway. cIAP1 and cIAP2 might serve as effective therapeutic targets.
研究领域:
微生物学
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免疫学
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胃肠病学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Qiaoxuan Wang,Qi Cheng,Ding Huang,Kefei Zhao,Qiaoju Hu,Min Liang,Yifan Xie,Huaxiang Wu,Changyou Gao
The inefficient lysosomal escape of small interfering RNA (siRNA) from immune cells remains a major barrier to therapeutic efficacy. To address this challenge, an innovative pH-triggered aggregation nanoplatform for enhanced siRNA delivery is developed. By using adamantane (Ad)-modified hyperbranched poly-L-lysine (HBPL-Ad) as a backbone, this nanoplatform incorporated acetalated β-cyclodextrin (β-ACD) as a pH-sensitive “gatekeeper”, together with siRNA to prepare physiologically stable aggregated nanoparticles (ANPs). Triggered by the acidic lysosomal microenvironment, the β-ACD hydrolysis exposed β-CD cavities to enable strong host-guest (β-CD/Ad) binding. This binding caused nanoparticle aggregation and subsequent mild lysosomal membrane permeabilization (LMP), facilitating efficient siRNA escape independent of the proton sponge effect. The ANPs demonstrated superior cellular uptake and significantly enhanced TNF-α silencing across macrophages, dendritic cells, and Jurkat immune cells in vitro. Intraperitoneal administration of ANPs loaded with TNF-α siRNA in a collagen-induced arthritis (CIA) model achieved 93% mRNA reduction and 95% protein reduction in joint TNF-α levels, significantly outperforming Lipo2000 (56% mRNA and 60% protein reduction), effectively attenuating synovitis and cartilage erosion without detectable systemic toxicity. This work establishes pH-triggered programmable aggregation as a potent and transformative strategy for overcoming immune cell delivery barriers, offering a promising clinically viable platform for RNAi-based immunotherapy.
研究领域:
纳米技术
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RNA干扰
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免疫治疗
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药物递送系统
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生物医学工程
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产品关联
DOI
高影响因子
EXPERIMENTAL NEUROLOGY
·
2024
·
IF 4.6
Jing Qiu,Yi-Han Wang,Xiu-Ming Wang,Hui-Sheng Chen
The pericytes (PCs) surrounding capillaries are vital regulators of capillary constriction. Persistent PC contraction results in the increased capillary constriction, therefore leading to the impaired cerebral blood flow (CBF) recovery after reperfusion and worsening the clinical outcomes in stroke patients. However, the potential determinants of PC functions during ischemia/reperfusion are poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit Delta (PIK3CD/PI3Kδ) is a crucial factor involved with neuronflammation during ischemic stroke. PI3Kδ has shown the expression in PCs, while its effect on PC functions has not been explored yet. In this study, a rodent ischemia/reperfusion model was established in C57BL/6 mice via transient middle cerebral artery occlusion and reperfusion (MCAO/R). The PI3Kδ expression in ischemic penumbra was remarkably upregulated following MCAO/R induction. PI3Kδ inhibitor CAL-101 improved the CBF recovery, ischemic brain injury, and suppressed capillary constriction in MCAO/R mice. Besides, the production of tumor necrosis factor alpha (TNF-α), an inducer for tissue injury, and the expression of transient receptor potential vanilloid type 2 (TRPV2), a channel protein permitting calcium (Ca 2+ ) uptake, were significantly reduced in ischemic penumbra after CAL-101 treatment. In vitro, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of PI3Kδ and TRPV2 in primary mouse PCs. CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca 2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Zhao Wenwen,Feng Haitao,Guo Shuhui,Han Yantao,Chen Xiuping
ICAM-1 overexpression and subsequent adhesion of leukocytes to endothelial cells play critical roles in the early stage of atherosclerosis. Danshenol A (DA) is an abietane-type diterpenoid isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. The mechanisms under its regulation of adhesion of molecular expression are explored. Here, the effect of DA on TNF-α-induced ICAM-1 expression was investigated in endothelial cells. TNF-α-induced ICAM-1 expression and subsequent adhesion of monocytes, as well as elevated reactive oxygen species (ROS) generation and NOX4 expression were all significantly reversed by DA, siNOX4 and NOX4 inhibitor GKT137831. Furthermore, TNF-α-induced ICAM-1 expression, which was increased via IKKβ/IκBα-mediated activation of NF-κB p65, was also inhibited by DA. Interestingly, NOX4 overexpression suppressed the ICAM-1 expression, and this finding may be ascribed to the activation of Nrf-2. Additionally, NF-κB inhibitor PDTC, siNOX4, or DA can decrease the TNF-α-induced ICAM-1 expression and suppress the adhesion of monocytes. In all, DA inhibited TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion to endothelial cells through the NOX4-dependent IKKβ/NF-κB pathway. Besides, NOX4 played dual role in regulating ICAM-1 expression via diverse signal pathway. This novel bioactivity will make DA a good candidate to be further explored for therapeutic or preventive application for atherosclerosis.
研究领域:
药理学
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心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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