CNS Neuroscience & Therapeutics
·
2026
·Vol. 32
·期 2
·e70787
·
IF 6.6
Shengnan Xiao,Lianmei Liu,Xuemei Qin,Lei Xu,Zhenyu Li,Zhi Chai
Cycloastragenol derivatives regulate the TLR4/NF‐κB/TERT signaling pathway and tyrosine metabolism, breaking the vicious cycle of “inflammation‐aging” and improving symptoms of Parkinson's disease. This study provides direction for the application of natural products in the development of PD drugs.
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高影响因子
MICROBIAL PATHOGENESIS
·
2024
·
IF 3.3
Zhikun Zhang,Dawei Shi,Haiwei Dou,Ruijie Wan,Qing Yuan,Peng Tu,Deli Xin
In previous study, lower levels of serum GP130 were reported in children with MPP. GP130 is an important signal transducer, the down regulation of which may influence host immune responses. In this study, we aimed to analyze the regulatory mechanism of GP130 during MP infection. Firstly, the mRNA and protein levels of GP130 both decrease and then increase with increasing multiplicity of infection (MOI: 1 to 40) of MP. The lowest levels of GP130 were detected at MOI of 5. Then, heat treated MP but not trypsin treated MP or MP extracted proteins show regulatory effect to the expression of GP130. These indicate that the down regulation of GP130 is related to protein mediate adhesion process of MP. Gene expression analysis revealed that MP affected apoptosis and the TLR4 pathway in infected cells, and the mRNA level of IL-6 was correlated with that of GP130. Further, Z-VAD-FMK (pan-caspase inhibitor) can suppress the apoptosis induced by MP infection and restore GP130 at protein level. Further studies revealed that MP infection promoted TLR4 internalization but did not activate the NF-κB pathway. The levels of surface TLR4 showed correlation with the transcription of IL-6 and GP130. TAK242 (TLR4 inhibitor) and PS341 (proteasome inhibitor) can restore the decreased transcription of GP130, both of which were able to promote NF-κB pathway activation in MP-infected cells. These suggested that the regulation of TLR4/NF-κB pathway and induced apoptosis post MP infection are involved in the down-regulation of GP130 at transcription and protein levels, respectively.
研究领域:
微生物学
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免疫学
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细胞生物学
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分子生物学
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PubMed
高影响因子
Microorganisms
·
2021
·Vol. 9
·期 9
·1983
·
IF 4.128
Shiyan Chen,Yanan Li,Bingxin Chu,Lanxin Yuan,Ning Liu,Yaohong Zhu,Jiufeng Wang
SalmonellaTyphimurium (S.Typhimurium) is an aggressive zoonotic pathogen that causes enteritis and diarrhea. Antibiotic therapy is still the primary method at present. However, the increasing emergence of multi-drug resistant bacteria weakens the therapeutic efficacy of antibiotics. Probiotics have been widely studied as an alternative antibiotic therapy. In this study, we established an IPEC-J2 cell model ofS.Typhimurium infection, aiming to determine the protective effect ofLactobacillus johnsoniiL531 (L. johnsoniiL531) onS.Typhimurium infection. As our data showed,S.Typhimurium infection resulted in a robust inflammatory response demonstrated by promoted protein levels of the inflammatory-related pathway (TLR4, MyD88, p-IκBα, and p-p65), increased cytokine levels of IL-6, IL-1β, IL-18, and TNF-α, and activated the NLRP3 inflammasome via promoting its assembly. However,L. johnsoniiL531 pre-incubation inhibited the activation of the above inflammatory signaling pathways and reduced the expression levels of pro-inflammatory cytokines. In addition,L. johnsoniiL531 alleviated the damage ofS.Typhimurium to tight junctions ZO-1, Occludin, and Claudin-1. In summary, our findings suggested thatL. johnsoniiL531 alleviatedS.Typhimurium-induced tight junction injury by inhibiting the TLR4/NF-κB/NLRP3 inflammasome signaling pathway.Keywords:SalmonellaTyphimurium;Lactobacillus johnsonii;TLR4;NF-κB;NLRP3 inflammasome;tight junctions
研究领域:
微生物学
·
免疫学
·
胃肠病学
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PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2020
·
IF 2.971
Zhaohui Wang,Zhi Chen,Bingsheng Li,Bo Zhang,Yongchao Du,Yuhang Liu,Yao He,Xiang Chen
Context Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects.Objective To explore the mechanisms underlying the effects of curcumin on RIF.Materials and methods Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-β1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation.Results In vivo, curcumin significantly improved the levels of BUN and Scr by 28.7% and 21.3%, respectively. Moreover, curcumin reduced the levels of IL-6, IL-1β and TNF-α by 22.5%, 30.3% and 26.7%, respectively, and suppressed vimentin expression in UUO mice. In vitro, curcumin reduced the expression of vimentin and α-smooth muscle actin in TGF-β1-induced HK-2 cells. In LPS-induced HK-2 cells, curcumin decreased the release of IL-6, IL-1β and TNF-α by 43.4%, 38.1% and 28.3%, respectively. In addition, curcumin reduced the expression of TLR4, p-PI3K, p-AKT, p-NF- κB and p-IκBα in both LPS- and TGF-β1-induced HK-2 cells.Discussion and conclusions Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-κB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.
研究领域:
肾病学
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药理学
·
分子生物学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Jia-Hui Cheng,Xiang Xu,Ying-Biao Li,Xu-Dong Zhao,Fumie Aosai,Su-Yun Shi,Cheng-Hua Jin,Jing-Shu Piao,Juan Ma,Hu-Nan Piao,Xue-Jun Jin,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is a known neurotropic protozoan that remains in the central nervous system and induces neuropsychiatric diseases in intermediate hosts. Arctigenin (AG) is one of the major bioactive lignans of the fruit Arctium lappa L. and has a broad spectrum of pharmacological activities such as neuroprotective, anti-inflammatory and anti- T. gondii effects. However, the effect of AG against depressive behaviors observed in T. gondii -infected hosts has not yet been clarified. In the present study, we analyzed the effects of AG against T. gondii -induced depressive behaviors in intermediate hosts using a microglia cell line (BV2 cells) and brain tissues of BALB/c mice during the acute phase of infection with the RH strain of T. gondii . AG attenuated microglial activation and neuroinflammation via the Toll-like receptor/nuclear factor-kappa B (NF-κB) and tumor necrosis factor receptor 1/NF-κB signaling pathways, followed by up-regulating the dopamine and 5-hydroxytryptamine levels and inhibiting the depression-like behaviors of hosts. AG also significantly decreased the T. gondii burden in mouse brain tissues. In conclusion, we elucidated the effects and underlying molecular mechanisms of AG against depressive behaviors induced by T. gondii infection.
研究领域:
神经科学
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药理学
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传染病学
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免疫学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Zhenhua Bian,Yuwen Qin,Lin Li,Lianlin Su,Chenghao Fei,Yu Li,Minmin Hu,Xiaowei Chen,Wei Zhang,Chunqin Mao,Xiaohang Yuan,Tulin Lu,De Ji
Ethnopharmacological relevance the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese herbal medicine, which has been widely used in traditional Chinese medicine (TCM) for treating intestinal diseases . It is also traditionally used as health product and medicine in Russia and other countries. However, the effect of SC ethanol extract on anti-ulcerative colitis (UC) has not been systematically studied yet. Aim of the study We investigated the protective effects and underlying action mechanisms of SC extract (SCE) for UC treatment. Materials and methods An animal model of UC induced by dextran sulfate sodium (DSS) was established. After oral administration of SCE, the Disease Activity Index (DAI) was calculated, the length of colon measured, levels of proinflammatory factors determined, and histopathology carried out to assess the therapeutic efficacy of SCE on UC. The effects of SCE on the toll-like receptor 4/nuclear factor-kappa B/nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 inflammasome (TLR4/NF-κB/NLRP3 inflammasome) signaling pathway were evaluated by western blotting . High-throughput sequencing was done to reveal the effect of SCE on the change of the gut microbiota (GM) in mice with DSS-induced colitis. Results SCE significantly reduced the DAI score, restored colon-length shortening, and ameliorated colonic histopathologic injury in mice with DSS-induced colitis. SCE inhibited the inflammatory response by regulating the TLR4/NF-κB/NLRP3 inflammasome pathway in mice with UC. SCE also maintained gut barrier function by increasing the levels of zonula occludens (ZO)-1 and occludin . 16S rRNA sequencing showed that SCE could reverse the GM imbalance caused by UC. Conclusions SCE can ameliorate DSS-induced colitis, and that its effects might be associated with suppression of the TLR4/NF-κB/NLRP3 inflammasome pathway and GM regulation, which may provide significant supports for the development of potential candidates for UC treatment.
研究领域:
药理学
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免疫学
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微生物学
·
传统中医
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PubMed
高影响因子
Food Science & Nutrition
·
2026
·Vol. 14
·期 4
·e71768
·
IF 5
Yunyun Zhi,Keli Zhou,Xueqing Huang,Yonghui Li,Ye Zhu,Yiqiang Xie,Shouzhong Ren
Gastric mucosal injury refers to the pathological changes characterized by congestion, edema, bleeding and erosion of the gastric mucosa caused by various factors. This condition is a significant feature of gastritis in which the inflammatory response plays a critical role in its pathogenesis. The herbal pair Daphniphyllum calycinum – Polygonum hydropiper (DCPH), known for its anti‐inflammatory and antioxidant properties, has been shown to alleviate gastric mucosal injury. This study aimed to elucidate the mechanism by which DCPH alleviates gastric mucosal injury by integrating network pharmacology with both in vivo and in vitro experimental validation. The results indicated that DCPH treatment significantly increased the antioxidant capacity of the cells and decreased the expression of inflammation‐related factors. DCPH suppressed macrophage M1 polarization while inducing apoptosis in damaged cells. Furthermore, DCPH diminished structural gastric mucosal damage and gastric inflammation. DCPH promotes autophagy by upregulating the expression of LC3II/I and Beclin1, and downregulating P62 accumulation, thereby inhibiting the TLR4/NF‐κB/NLRP3 signaling pathway and M1 polarization, and reducing the release of inflammatory factors. However, these effects can be reversed by the autophagy inhibitor chloroquine (CQ). In conclusion, DCPH alleviates gastric mucosal injury via regulating autophagy and targeting TLR4/NF‐κB/NLRP3, thereby offering insights for the treatment of gastrointestinal diseases. The schematic diagram illustrated the proposed mechanism of DCPH in mouse macrophages. DCPH promotes autophagy to suppress the TLR4/NF‐κB/NLRP3 pathway and M1 polarization, thereby attenuating cellular oxidative stress and inflammation.
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高影响因子
BASIC RESEARCH IN CARDIOLOGY
·
2016
·Vol. 112
·期 1
·1-15
·
IF 6.038
Han Jibo,Zou Chunpeng,Mei Liqin,Zhang Yali,Qian Yuanyuan,You Shengban,Pan Yong,Xu Zheng,Bai Bin,Huang Weijian,Liang Guang
Angiotensin II (Ang II) induces cardiac inflammation and remodeling. Emerging evidence indicates that Ang II may utilize the Toll-like receptor 4 (TLR4) signaling pathway in mediating pro-inflammatory and pro-fibrotic activities. However, the precise mechanism is poorly understood. Myeloid differentiation 2 (MD2), a molecule that physically binds to TLR4, confers lipopolysaccharide responsiveness and may also be involved in mediating the actions of Ang II. We hypothesize that MD2 plays an essential role in cardiac inflammation and remodeling induced by local Ang II, and inhibition of MD2 can attenuate Ang II-induced cardiac dysfunction. Using a specific small molecule MD2 blocker L6H21 and the MD2 knockout mice, we show that MD2 deficiency significantly reduces cardiac inflammation and subsequent fibrosis, hypertrophy, and dysfunction in mice challenged with subcutaneous injection of Ang II. In rat cardiomyocyte-like H9c2 cells as well as rat primary cardiomyocytes, inhibition of MD2 by L6H21 or siRNA knockdown suppressed the Ang II-induced TLR4 signaling pathway activation including MyD88 recruitment, and reduced cardiomyocyte hypertrophy and matrix protein expression. These pro-inflammatory activities of Ang II were independent of the AT1 receptor. Finally, we demonstrated the direct interaction between Ang II and MD2 protein via hydrogen bonds on Arg-90, Glu-92, and Asp-100. Ang II produces an inflammatory response and cardiac remodeling by directly binding to MD2, activating MD2/TLR4 complex, and recruiting MyD88. MD2 may be a new therapeutic target for Ang II-mediated cardiac inflammation and remodeling.
研究领域:
心脏病学
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免疫学
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分子生物学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Junjun Liu,Naibo Feng,Xinyu Jiang,Xirui Xin,Yubo Hou,Zhende Jiang,Laijin Lu,Weixian Yu,Bai Yang
Periodontitis is a common chronic inflammatory disease and the local accumulation of excessive reactive oxygen species (ROS) could cause oxidative damage to periodontal tissues. Thus, antioxidative therapy is considered to be the promising strategy for treating periodontitis. However, highly efficient antioxidant activity of biomaterials with low cost, ease of synthesis, and good biocompatibility are still highly desired. Here amylopectin from maize (AFM)-derived carbonized polymer dots (AFM-CPDs-240) with excellent antioxidant activity, good water solubility and biosafty is parepared. Detailed characterizations identify that the antioxidant properties and formation mechanism of AFM-CPDs, and antioxidant activity of AFM-CPDs-240 is much higher than Trolox (a hydrophilic derivative of vitamin E) due to the large contents of conjugated C=C and C=O. Besides, in vitro and in vivo experiments suggest AFM-CPDs-240 could effectively alleviate inflammatory response, inhibit alveolar bone resorption and promote bone formation, showing excellent therapeutic effects on periodontitis. Moreover, the label-free proteomics and western blot results demonstrate AFM-CPDs-240 could accelerate the recovery of periodontitis by blocking TLR4/NF-κB (Toll-like receptor 4/ nuclear factor-kappa B) signaling pathway. This study will develop a simple approach to design highly efficient antioxidant carbon dots with good biocompatibility, and also provide a new promising nanoplatform for treating diseases associated with ROS.
研究领域:
牙医学
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材料科学
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生物化学
·
药理学
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高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Zhensong Jiang,Jianru Zhang
EXs (Exosomes) secreted by mesenchymal stem cells (MSCs) have the potential to treat spinal cord injury (SCI), this study aimed to further explore the therapeutic effect of EXs on SCI. Firstly, EXs were extracted from MSCs and analyzed with a transmission electron microscope. Next, MSCs with or without the miR-145-5p plasmid were injected into the SCI rat model, and then rat damage was evaluated by BBB score, HE staining and Nissl staining. And then Luciferase experiment verified the targeting relationship between miR-145-5p and TLR4. Furthermore, LPS-induced PC12 cells were established and incubated with Dil-labeled MSC-EXs to explore their effects on cell viability, apoptosis and inflammation through MTT, flow cytometry and ELISA, respectively. In addition, expressions of TLR4/NF-κB signaling pathway related factors were measured by qRT-PCR and Western blot. The results showed that after MSCs were successfully isolated, the existence of EXs in MSCs was confirmed. Moreover, MSC-EXs containing miR-145-5p improved functional recovery and reduced histopathological injury and inflammation in SCI rats. And MSC-EXs promoted miR-145-5p expression in spinal cord tissue and inhibited TLR4/NF-κB pathway activation in SCI rats. MSC-EXs inhibited LPS-induced inflammatory response and activation of the TLR4/NF-κB pathway in PC12 cells. In addition, we also found that miR-145-5p specifically targeted TLR4. TLR4 overexpression significantly reversed the effect of EX-miR-145-5p on maintaining PC12 cell viability, inhibiting apoptosis and inflammatory response, and activating TLR4/NF- κB pathway. In conclusion, mesenchymal stem cell-derived EXs containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4/NF-κB signaling pathway.
研究领域:
神经科学
·
干细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Shengyu Li,Yuting Pan,Gang Wang,Jintao Fang,Jingwei Wang,Youqi Ji,Zhenhao Dong,Ping Ling,Xianghou Zheng,Yao Gao,Qing Xia,Xia Liu,Wei Zhang
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease characterized by large-intestinal mucosal ulceration and persistent inflammation, which manifests as bloody diarrhea and abdominal pain and may elevate colorectal cancer risk. Polysaccharide-based hydrogels are attractive candidates for local rectal therapy of UC owing to favorable biocompatibility; however, their therapeutic performance is compromised by short lesion residence time caused by continuous intestinal peristalsis. Herein, we fabricated a muco-adaptive multifunctional hydrogel (B-ODT/CM@PF) constructed via dual-dynamic cross-linking of boronate-diol ester bonds and Schiff-base imine bonds for local treatment of UC. The carboxymethyl chitosan component contributes to rapid local hemostasis and epithelial barrier repair, whereas boron-complexed oxidized dextran confers broad-spectrum bactericidal capacity by disrupting bacterial membrane integrity. Benefiting from boronate-diol interactions, paeoniflorin (PF) is anchored within hydrogel networks to realize inflammation-triggered sustained release. The released PF targets the TLR4-NF-κB signaling axis to drive macrophage M2 polarization and mitigate excessive intestinal inflammatory responses. Moreover, B-ODT/CM@PF rescues the integrity of the intestinal mucosal barrier by inhibiting MLCK activation and preserving tight-junction proteins expression, further ameliorating colitis manifestations. Collectively, this dual-crosslinked bioadhesive hydrogel achieves synergistic functions including mucosal adhesion, hemostasis, antibacterial activity, immunomodulation and barrier reconstruction, providing a promising strategy for local treatment of UC.
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高影响因子
International Heart Journal
·
2022
·Vol. 63
·期 3
·578-590
·
IF 1.823
Haibo Du,Lianqin Ding,Tian Zeng,Di Li,Li Liu
Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.
研究领域:
分子生物学
·
心脏病学
·
细胞生物学
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高影响因子
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