Food Bioscience
·
2024
·
IF 4.8
Danliangmin Song,Jingqi Cheng,Kai Dong,Shiyu Liu,Chaoxin Man,Shiqian Fu,Xinyan Yang,Qianyu Zhao,Yujun Jiang
Cronobacter sakazakii is a facultative anaerobic gram-negative pathogen that has attracted widespread attention for causing necrotizing enterocolitis in infants (premature and low-weight newborns) by contaminating powdered infant formula. Several studies have found that the antibiotic tolerance of Cronobacter sakazakii isolated from food sources is increasing, thereby markedly increasing the difficulty of clinical treatment of Cronobacter sakazakii infection. At present, most studies are focused on clarifying the pathogenicity of Cronobacter sakazakii , but there is still a gap in the study of necrotizing enterocolitis in neonatal rats caused by Cronobacter sakazakii with different antibiotic tolerance. To fill this gap, we analyzed and compared the ability of Cronobacter sakazakii induced by different classes of antibiotics to induce necrotizing enterocolitis in neonatal rats by mediating TLR4-NLRP3-IL-1β pathway. In the results, Cronobacter sakazakii acquired tolerance to aminoglycosides, quinolones and cephalosporins, and caused more inflammatory damage in neonatal rats, improved the ability of mediating TLR4-NLRP3-IL-1β pathway to induce necrotizing enterocolitis. Compared with the XS001 group, the NEC scores of neonatal rats in XS001-Amp, XS001-Ami, XS001-Ofl and XS001-Ceo groups were increased by 8.3%, 58.3%, 50.0% and 58.3%. The acquisition of penicillin and tetracycline tolerance had little effect on the ability of Cronobacter sakazakii to induce necrotizing enterocolitis in neonatal rats. The ability of Cronobacter sakazakii to induce necrotizing enterocolitis in neonatal rats was significantly different due to the type and tolerance of antibiotics.
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MOLECULAR MEDICINE
·
2025
·Vol. 31
·期 1
·1-20
·
IF 6.4
Peng Shuaijun,Su Pan,Liu Liming,Li Zibo,Liu Yuan,Tian Lei,Bai Ming,Xu Erping,Li Yucheng
Background The dysregulation of neuroinflammation triggered by imbalance of microglia M1/M2 polarization is a key pathogenic factor and closely associated with occurrence of depression. Formononetin (FMN), a natural non-steroidal isoflavonoid, has been confirmed to exhibit remarkable anti-inflammatory efficacy, but the impact of FMN on depression and the underlying antidepressant mechanisms are still not fully understood. This study aimed to investigate whether the antidepressant effect of FMN is involved in modulating microglia polarization, and if so, what are the underlying mechanisms.Methods Lipopolysaccharide (LPS)-induced depressive mice were used to study antidepressant mechanisms of FMN. Microglia cell line BV2 stimulated by LPS was employed to investigate pharmacological mechanisms of FMN. Effects of FMN on neuronal damage were detected by H&E, Nissl and Golgi staining. The efficacy of FMN were evaluated by immunostaining and western blots in vivo and vitro. In addition, molecular docking, luciferase reporter assay, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to confirm the direct target of FMN.Results Our results showed that FMN significantly reverses depression-like behaviors, alleviates neuroinflammation and neuronal damage, rebalances M1/M2 polarization, inhibits NLRP3 inflammasome and enhances microglial autophagy level in prefrontal cortex of LPS-induced depressive mice. In vitro assays, results unraveled that autophagy inhibitor chloroquine (CQ) blocks effects of FMN on inhibiting NLRP3 inflammasome and rebalancing M1/M2 polarization. Moreover, PPARα is identified as a direct target of FMN and FMN can activate PPARα-mediated autophagy. Furtherly, combination PPARα agonist (WY14643) with FMN had no significant additive effects on inhibiting NLRP3 inflammasome and rebalancing M1/M2 polarization, whereas PPARα antagonist (GW6471) abrogated these pharmacologic effects of FMN in BV2. Importantly, GW6471 exhibited similar pharmacologic effects to abolish antidepressant effect of FMN in LPS-induced depressive mice.Conclusion Our study firstly demonstrated that FMN can rebalance microglia M1/M2 polarization and inhibit NLRP3 inflammasome, with the involvement of activating PPARα-mediated autophagy to ameliorate depression-like behaviors, which provides a novel view to elucidate antidepressant mechanisms of FMN and also offers a potential therapeutic target for depression.
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JOURNAL OF MOLECULAR MEDICINE-JMM
·
2024
·
IF 4.8
Wang Pengtao,Tao Wei,Li Qiujie,Ma Wanting,Jia Wei,Kang Yuting
Indole-3-aldehyde (I3A) is an intestinal microbial metabolite that regulates inflammation in various inflammatory diseases; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the anti-inflammatory effects and molecular mechanisms of I3A in COPD. We constructed in vivo models using cigarette smoke (CS)-stimulated mice and in vitro models using cigarette smoke extract (CSE)-stimulated MH-S cells. The results demonstrated that I3A significantly alleviated bronchial obstruction in mice with COPD and reduced the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, I3A decreased the levels of matrix metalloproteinases MMP2, MMP12, and inhibited the NF-κB p65/NLRP3 pathways. Further investigation revealed that I3A inhibited NF-κB activity by suppressing p65 phosphorylation and nuclear translocation in CSE-stimulated MH-S cells. The activation of the NF-κB and NLRP3 signaling pathways is mediated by histone deacetylase 5 (HDAC5) and HDAC6, both of which are inhibited by I3A. Subsequent experiments indicated that aryl hydrocarbon receptor (AHR) knockdown attenuated the inhibitory effect of I3A on pro-inflammatory cytokines and the HDACs/NF-κB/NLRP3 signaling pathways, highlighting the dependence of I3A's anti-inflammatory effects on the AHR receptor. Key messages
I3A effectively reduced lung inflammation in COPD mice by inhibiting the NF-κB pathway.
In CSE-stimulated MH-S cells, I3A suppressed p65 phosphorylation and nuclear translocation, thereby inhibiting NF-κB activity.
The activation of the NF-κB/NLRP3 pathways by HDAC5 and HDAC6 was diminished by I3A.
Through the activation of the AHR receptor, I3A suppressed the activities of HDAC5/6, leading to a decrease in inflammatory factor levels.
Graphical abstract
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Journal of Functional Foods
·
2025
·
IF 4
Peng Chen,Wenhao Xiao,Fanzhao Zou,Jiexin Lei,Fuchao Chen,Ruhong Zhang
This study explored the effects of methylated urolithin A (mUro A), on lipopolysaccharide (LPS)-induced cognitive impairment and anxiety- and depression-like behaviors, and their molecular mechanism. mUro A significantly mitigated cognitive dysfunction, anxiety- and depression-like behaviors. Furthermore, mUro A improved activities of antioxidative enzymes, regulated the release of inflammatory factors, inhibited the LPS-induced generation of Aβ 1 – 42 and restored the cholinergic system balance in the AD mouse brain. Additionally, mUro A markedly attenuated microglial activation by inhibiting the Drp1/HK1/NLRP3 pathway, thereby suppressing mitochondrial inflammation. This was evidenced by the downregulation of p-Drp1 (s616), VDACs, NLRP3, ASC, cleaved caspase 1, IL-18, and IL-1β, alongside the upregulation of HK1 expression. In conclusion, mUro A mitigates AD-associated cognitive deficits by inhibiting the Drp1/HK1/NLRP3 pathway and suppressing mitochondrial inflammation.
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Frontiers in Nutrition
·
2022
·
IF 6.59
Zhenhui Chen,Ziyu Tang,Jingjing Kong,Lixuan Chen,Jiaxin Liu,Yunting Li,Wanwen Huang,Wendan Li,Junlin Wu,Wei Zhao,Xiaojing Meng,Hongying Fan
Pb poisoning affects infant growth and development. However, dimercaptosuccinic acid (DMSA) as the current therapy for Pb poisoning exerts relatively significant toxic side effects in infants. Therefore, identifying a non-toxic treatment in this regard is particularly important. In this study, we aimed to investigate the therapeutic effect of an infant feces-derived probiotic strain, Lactobacillus casei SYF-08 (SYF-08), on Pb poisoning in young mice. The Pb levels in the organisms were detected via inductively coupled plasma mass spectrometry, while the therapeutic effect of SYF-08 on Pb-induced neural system damage was explored via the Morris water maze test, hematoxylin-eosin staining, and immunohistochemistry. Additionally, the molecular mechanisms underlying the protective effects of SYF-08 against Pb-induced intestinal damage were also explored via histological staining, 16S rRNA sequencing, untargeted metabolomics, qRT-PCR, and western blotting. In vivo experiments revealed that SYF-08 reduced blood and bone Pb levels and increased urinary Pb excretion. Additionally, SYF-08 alleviated Pb-induced pathological damage to the brain and ultimately improved the learning and cognitive abilities of the young mice. This treatment also restored intestinal microflora dysbiosis, regulated bile acid metabolism, and inhibited the FXR-NLRP3 signaling pathway. It also resulted in fewer adverse events than the DMSA treatment. In conclusion, our results provided valuable insights into the therapeutic role of SYF-08 in Pb poisoning and also suggested that its administration can significantly alleviate the Pb-induced damage.
研究领域:
微生物学
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毒理学
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神经科学
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代谢组学
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Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Wang Hetong,Song Laiyu,Ju Wenhui,Wang Xuguang,Dong Lu,Zhang Yining,Ya Ping,Yang Chun,Li Fasheng
PM 2.5 is the main particulate air pollutant whose aerodynamic diameter is less than 2.5 micron. The inflammation of various respiratory diseases are associated with PM 2.5 inhalation. Pro-inflammatory cytokine IL-1β generated from effected cells usually plays a crucial role in many kinds of lung inflammatory reactions. The exacerbation of Th immune responses are identified in some PM 2.5 related diseases. To elucidate the underlying mechanism of PM 2.5 -induced acute lung inflammation, we exposed Balb/c mice to PM 2.5 intratracheally and established a mice model. Acute lung inflammation and increased IL-1β expression was observed after PM 2.5 instillation. Regulatory factors of IL-1β (TLR4/MyD88 signaling pathway and NLRP3 inflammasome) participated in this lung inflammatory response as well. Treatment with compound essential oils (CEOs) substantially attenuated PM 2.5 -induced acute lung inflammation. The decreased IL-1β and Th immune responses after CEOs treatment were significant. PM 2.5 may increase the secretion of IL-1β through TLR4/MyD88 and NLRP3 pathway resulting in murine airway inflammation. CEOs could attenuate the lung inflammation by reducing IL-1β and Th immune responses in this model. This study describes a potentially important mechanism of PM 2.5 -induced acute lung inflammation and that may bring about novel therapies for the inflammatory diseases associated with PM 2.5 inhalation.
研究领域:
免疫学
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呼吸医学
·
环境健康
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JOURNAL OF AUTOIMMUNITY
·
2024
·
IF 7.9
Qishun Geng,Jiahe Xu,Xiaoxue Cao,Zhaoran Wang,Yi Jiao,Wenya Diao,Xing Wang,Zihan Wang,Mengxiao Zhang,Lu Zhao,Lei Yang,Tingting Deng,Bifa Fan,Yuan Xu,Lansi Jia,Cheng Xiao
Introduction Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint inflammation and bone damage, that not only restricts patient activity but also tends to be accompanied by a series of complications, seriously affecting patient prognosis. Peroxisome proliferator-activated receptor gamma (PPARG), a receptor that controls cellular metabolism, regulates the function of immune cells and stromal cells. Previous studies have shown that PPARG is closely related to the regulation of inflammation. However, the role of PPARG in regulating the pathological processes of RA is poorly understood. Materials and methods PPARG expression was examined in the synovial tissues and peripheral blood mononuclear cells (PBMCs) from RA patients and the paw of collagen-induced arthritis (CIA) model rats. Molecular biology experiments were designed to examine the effect of PPARG and cannabidiol (CBD) on RAW264.7 cells and CIA rats. Results The results reveal that PPARG accelerates reactive oxygen species (ROS) clearance by promoting autophagy, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation. Notably, CBD may be a promising candidate for understanding the mechanism by which PPARG regulates autophagy-mediated inflammation. Conclusions Taken together, these findings indicate that PPARG may have a role for distinguishing between RA patients and healthy control, and for distinguishing RA activity; moreover, PPARG could be a novel pharmacological target for alleviating RA through the mediation of autophagy. CBD can act as a PPARG agonist that alleviates the inflammatory progression of RA.
研究领域:
免疫学
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风湿病学
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药理学
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细胞生物学
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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
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传统中医
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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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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Zijun Zhou,Yinli Xu,Xiong Xiao,Tao Huang,Jikai Zhao,Yuting Huang,Guoxin Zhang,Bo Xing,Qiusheng Zhao,Zijun Cao,Zhishang Wang,Zongtao Yin,Liming Yu,Huishan Wang
Background and purpose Our previous clinical study showed that berberine could reduce the occurrence of postoperative atrial fibrillation (AF), but the underlying mechanism remains unknown. Additionally, the effect of SIRT6 in the pathogenesis of AF and whether the anti-arrhythmic effects of berberine are associated with SIRT6 regulation remain uncovered. This study aimed to investigate the role of SIRT6 in the occurrence of AF and the pharmacological effect of berberine on atrial remodeling and AF susceptibility with a focus on SIRT6-AMPK signaling. Methods Bioinformatics tools and human atrial sample analysis were conducted to investigate the potential mechanisms. Murine AF model was induced by angiotensin II (Ang II) infusion with or without the treatment of berberine and the adeno-associated virus carrying SIRT6 or SIRT6-specific short hairpin RNA. The protective effect and the underlying mechanisms were examined. Results NLRP3 inflammasome-mediated inflammatory signaling in atrial tissue was activated, and SIRT6 activity was inhibited in AF patients. Berberine dose-dependently improved atrial structural and electrical remodeling in Ang II-induced mice. Moreover, berberine enhanced atrial antioxidative stress capacity and reduced NLRP3 inflammasome activation. SIRT6 overexpression mimicked these actions. Berberine-mediated SIRT6-AMPK signaling activation was inhibited by SIRT6 knockdown, and berberine-mediated inhibition of NLRP3 inflammasome signaling was compromised. Conclusion These results demonstrate that activation of SIRT6-AMPK signaling protects against Ang II-induced atrial remodeling and AF susceptibility. Berberine prevents Ang II-induced atrial injury by inhibiting NLRP3 inflammasome activation through the SIRT6-AMPK signaling pathway. Its potential as a preventive or therapeutic agent warrants further clinical investigation.
研究领域:
心脏病学
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分子生物学
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药理学
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炎症研究
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International Journal of Nanomedicine
·
2023
·
IF 8
Qi Lou,Lu Pan,Shengjin Xiang,Yueting Li,Jiahui Jin,Jingyang Tan,Baoshan Huang,Kaihui Nan,Sen Lin
Introduction Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.
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Diabetology & Metabolic Syndrome
·
2023
·Vol. 15
·期 1
·1-13
·
IF 4.8
Li Tianrong,Yang Jingjing,Tan Anjun,Chen Hewen
Background Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown.Methods In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results.Results We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets.Conclusion We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
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