MOLECULAR NUTRITION & FOOD RESEARCH
·
2023
·
IF 5.2
Xiaoying Tian,Xi Liang,Hong He,Qingyu Cui,Qiqi Liu,Rongbo Fan,Tongjie Liu,Huaxi Yi,Pimin Gong,Qingzhu Wang,Lanwei Zhang
Scope Food allergy has become a world recognized public health problem due to its versatility and lack of efficacious methods for its treatment. Probiotics supplement is a potential way to prevent food allergy. Methods and results In this study, potential strains are screen out by peripheral blood mononuclear cells (PBMCs), and their abilities of alleviating food allergy are examined using a mouse model induced by ovalbumin (OVA). The results show that six strains increase ratio of interferon-γ (IFN-γ)/interleukin (IL)-4 secreted by PBMCs with good abilities in intestinal adhesion and gastrointestinal tolerance. Oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) attenuates allergic responses in allergy mice, including allergic symptoms, mast cells aggregation and activity, serum OVA-special-immunoglobulins E (OVA-sIgE) production. KV9 and FN3 upregulate the production of IFN-γ/IL-4 in splenocytes, increase the genes and proteins expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (Myd88) and interferon regulatory factor (IRF)-1 in allergic mice spleen, and decrease the IRF-4. Conclusion The study demonstrates that KV9 and FN3 possess anti-allergic activities via activation of TLR4 pathway and modulating the expression of IRF-1 and IRF-4 which leads to T helper type 1 (Th1)/T helper type 2 (Th2) cell immunology balance.
研究领域:
免疫学
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微生物学
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过敏
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cancer Management and Research
·
2020
·
IF 2.886
Weixu Luo,Yuanshan Han,Pan Meng,Qin Yang,Hongqing Zhao,Jia Ling,Yuhong Wang
Background Breast cancer is one of the most common cancer with high risk in females all over the world. It is usually complicated with depression, which can further accelerate the development and progression of breast tumors. We aim to identify a new drug and identify its functional mechanism in the regulation of hippocampal microglia (MG) in breast cancer complicated with depression (BCCD). Methods The activation model of MG was established by treatments from corticosterone (CORT) or lipopolysaccharides (LPS). The inhibitory effects of resatorvid on MG were investigated by CCK-8, ROS, immunofluorescence, TUNEL, scratch test, ELISA, RT-qPCR and Western blot. BCCD animal model was established using 4T1 inflammatory breast cancer cells and CORT treatment in vitro. Open field experiment (OFE), tail suspension test (TST), ELISA, RT-qPCR and Western blot experiments were utilized to examine the effects of resatorvid on the animal model in vivo. Results The cell viability and migration ability of the BCCD model group were suppressed. The expressions of inflammatory factors, ROS, and the apoptotic rate of the BCCD model group were up-regulated, in contrast to the control group. The expressions related to the TLR4/NF-κB/NLRP3 signaling in the BCCD model group were also elevated. Resatorvid reversed the above changes, which showed good therapeutic effects in depression-related behavioral changes, tumor treatment, and blood–brain barrier function. Conclusion In summary, resatorvid inhibited the activation of hippocampal MG in BCCD by regulating TLR4/NF-κB/NLRP3 signaling pathway.
研究领域:
肿瘤学
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神经科学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Lei Jin,Xiang Peng,Zeng Shengmei,Chen Le,Zhang Lei,Yuan Zhiyi,Zhang Jun,Wang Tingting,Yu Ruihong,Zhang Wanping,Ibrahim Issa Issoufou,Ma Limei,Yu Chao
Tetramethylpyrazine (TMP), a Chinese traditional herbal extraction widely used in treating cardiovascular diseases, could attenuate vascular endothelial injuries, but the underlying mechanism remains incomprehensive. Vascular glycocalyx coating on the endothelium would be damaged and caused endothelial dysfunction in the inflammatory microenvironment, which was the initial factor of morbidity of many vascular diseases, such as atherosclerosis (AS). Here, we thoroughly investigated the molecular mechanism of TMP on vascular endothelial glycocalyx in the LPS-induced inflammatory model both in vitro and in vivo. Results showed that pretreatment with TMP significantly inhibited glycocalyx degradation and monocytes adhesion to the endothelial process. Moreover, TMP pretreatment inhibited the expression of HPSE1 (a major degrading enzyme of endothelial glycocalyx), Toll-like receptor 4 (TLR4), and the translocation of nuclear factor kappa B p65 (NF-κB p65). We were utilized withTLR4 siRNA, NF-κB inhibitor, and HPSE1 overexpression analysis confirmed TMP’s protection on endothelial glycocalyx injury, which further contributed to the monocyte-endothelial adhesion process. It was indicated that TMP might suppress glycocalyx degradation through TLR4/NF-κB/HPSE1 signaling pathway. Taken together, our results enriched the occurrence molecular mechanism of glycocalyx shedding and molecular regulation mechanism of TMP in protecting integrity of the glycocalyx structure during inflammation. As TMP is currently used in clinical applications, it may be considered a novel strategy against atherosclerosis through its ability to protect endothelial glycocalyx.
研究领域:
心血管疾病
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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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产品关联
DOI
PubMed
高影响因子
TOXICOLOGICAL SCIENCES
·
2016
·Vol. 153
·期 2
·303-315
·
IF 3.88
Fu Juanli,Shi Qiong,Song Xiufang,Liu Zixuan,Wang Yawen,Wang Yuxin,Song Erqun,Song Yang
Tetrachlorobenzoquinone (TCBQ) is a confirmed active metabolite of a well-known environmental pollutant pentachlorophenol (PCP). Unfortunately, there is insufficient knowledge present available on TCBQ’s toxicity. Our previous studies indicated that TCBQ induces inflammatory response in vivo and in vitro; however, its exact mechanism needs further investigation. Toll-like receptors (TLRs) play a crucial role in conveying of inflammatory signaling, whilst high-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear protein that regulates inflammation. Indeed, this study demonstrated that TCBQ induces the secretion/translocation of HMGB1, which in turn activates its receptors, TLR family gene (especially TLR4) and receptor for advanced glycation end-products (RAGE) expressions. Consistently, the binding affinity of HMGB1 with its receptors also increased. In the case of HMGB1 or TLR4 deficiency, there were decreases in TCBQ-induced neuroinflammatory cytokine production and neuropathological changes, eg, neuronal loss, astrocyte and macrophage cells activation. Moreover, we found the mobilization of TLR4 into lipid rafts occurs in response to TCBQ exposure, lipid rafts disruptors weakened this effect, suggested lipid rafts play an essential role for TLR4-mediated signal transduction and target inflammatory cytokines expressions. In summary, our current findings revealed a previously unknown mechanism of TCBQ-induced neurological inflammation related to HMGB1-TLR4 signaling.
研究领域:
毒理学
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神经科学
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免疫学
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环境健康
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2025
·
IF 7.3
Zixu Li,Yacan Gong,Emmanuel Sunday Okeke,Dan Li,Yao Chen,Weiwei Feng,Ting Zhao,Liuqing Yang,Guanghua Mao,Xiangyang Wu
Typical plasticizer dibutyl phthalate (DBP) has been demonstrated to induce hepatotoxicity in zebrafish, but the underlying molecular mechanisms remain incompletely elucidated. Numerous studies have shown that ferroptosis is involved in the pathophysiological progression of hepatic disease. However, it remains unclear whether ferroptosis is involved in the DBP-induced hepatotoxicity in zebrafish. Initially, histopathological analyses have preliminarily confirmed that DBP can activate inflammatory responses in the zebrafish liver. Further investigation revealed that DBP induces ferroptosis in the zebrafish liver, characterized by iron overload, lipid peroxidation, and aberrant activation of ferroptosis pathways. Furthermore, DBP exposure induced ferroptosis, disrupting cell membranes and subsequent release of HMGB1, which are sensed by immunocytes TLR4/NF-κB signaling pathways, thereby activating the innate immune response in a context-dependent manner. Moreover, the ferroptosis inhibitor Fer-1 effectively rescues the activation of HMGB1-TLR4/NF-κB-mediated immune processes. Overall, this work enriches the molecular mechanism of DBP-induced zebrafish liver inflammatory damage and provides a reliable biomarker for future environmental risk assessment of DBP.
研究领域:
环境毒理学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2021
·
IF 4.079
Dongzhu Zhang,Xue Shen,Ke Pang,Zhao Yang,Anyong Yu
Aims Numerous evidence demonstrated that macrophage mediated inflammation contributed to brain injury following ICH, but the molecular mechanism had not been well studied. V-set immunoglobulin-domain-containing 4 (VSIG4), specifically expresses in resting tissue-resident macrophages, can deliver anti-inflammatory signals into various inflammatory diseases. However, the role of VSIG4 on ICH has not been reported. Methods In the present study, we investigated the levels of VSIG4 in macrophages following ICH. Furthermore, Macrophage M1/M2 polarization, pro-inflammatory cytokine production, BBB disruption, brain water content and neurological function were examined in ICH mice. In addition, TLR4/NF-κβ downstream signals were also analyzed. Results The results showed that VSIG4 levels of macrophage decreased following ICH, leading to macrophage M1 polarization. Up-regulation of VSIG4 inhibited macrophage M1 polarization, pro-inflammatory cytokine production, BBB disruption, as well as neurological deficits. Up-regulation of VSIG4 attenuated macrophage TLR4 levels following ICH. Co-IP demonstrated that VSIG4 could interact with TLR4 and inhibit its expression. Conclusions Our data demonstrated that VSIG4 was negatively correlated with TLR4 and involved in the pathogenesis of ICH, which prevented brain injury and attenuated deleterious inflammatory responses following ICH. In addition, the anti-inflammatory effect of VSIG4 was mainly through the blockage of TLR4/NF-κβ signaling.
研究领域:
神经科学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2022
·Vol. 36
·期 4
·1678-1691
·
IF 6.388
Shiquan Chang,Xin Li,Yachun Zheng,Huimei Shi,Di Zhang,Bei Jing,Zhenni Chen,Guoqiang Qian,Guoping Zhao
Switching microglial polarization from the M1 to M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS). Uncontrolled activation of TLR4 has been proven to trigger chronic inflammation. Kaempferol, a dietary flavonoid, is known to have anti-inflammatory properties. This study is aimed to investigate the analgesic and anti-inflammatory effects and the underlying mechanisms of kaempferol, which were explored with an NP model in vivo and LPS-induced injury in microglial BV2 cells in vitro. The levels of proinflammatory cytokines were evaluated. H&E staining and immunohistochemistry were used to assess the sciatic nerve condition after chronic constriction injury surgery. Western blotting and immunofluorescence were used to determine whether TLR4/NF-ĸB signaling pathway plays a major role in kaempferol-mediated alleviation of neuroinflammation. Quantitative real-time polymerase chain reaction and flow cytometry were used to examine the modulator effect of kaempferol on microglial M1/M2 polarization. We found that kaempferol treatment can significantly reduce NP and proinflammatory cytokine production. Kaempferol attenuated the activation of TLR4/NF-κB pathways in LPS-activated BV2 cells. The analgesic effects of kaempferol on NP may be due to inhibition of microglia activation and switching the M1 to M2 phenotype.
研究领域:
神经科学
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药理学
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炎症
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疼痛管理
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Zuyue Li,Shasha Wang,Mahmoud Abou-Elsoud,Yijie Li,Houchuntai Wang,Meiyu Liu,Wei Hu,Dong Uk Ahn,Xi Huang
NVMEERKIK, a peptide derived from ovalbumin, exhibited remarkable immunomodulatory activity. This study investigated the effect of simulated gastrointestinal digestion on its structure and bioactivity. NVMEERKIK was found to be unstable against gastrointestinal enzymes and completely degraded into NVME, NVMEE, KIK, K, and R. Among these, NVME, which constituted 90.90% of the digest, was synthesized and demonstrated a superior immune-enhancing activity than NVMEERKIK. Specifically, NVME improved phagocytosis, NO production, and TNF-α content in RAW264.7 cells by 1.31–15.86%, 17.17–122.08%, and 0.36–16.76%, respectively. TLR4 inhibition and immunofluorescence assays revealed the strong TLR4 activation and recognition capacities of both peptides. Furthermore, the Western blot results showed that NVMEERKIK and NVME activated the MAPK/NF-κB pathway by upregulating ERK, JNK, p38, and p65, leading to enhanced activation of RAW264.7 cells. The improved immune-enhancing activity of NVMEERKIK after digestion highlighted its potential as an immunomodulatory peptide for functional food applications.
研究领域:
食品科学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2025
·
IF 2.5
Xiaoli Liu,Shan Wang,Chuangfu Kuang,Yuwen Deng,Shuaicai Yuan,Juying Zou
We aim to explore the key metabolic components and underlying mechanisms of the Bushen Huoxue Formula (BH) in treating Osteoarthritis (OA). The mouse knee OA model was constructed using the destabilization of the medial meniscus method. OA mice were orally administered the BH. Mouse cartilage damage was assessed. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS), network pharmacology analysis and molecular docking were employed to analyze the serum metabolite components and target protein of BH. After lipopolysaccharide (LPS) treatment, different concentrations of β-Estradiol 3-acetate were added to primary chondrocytes. Flow cytometry was utilized for detecting cell apoptosis. The Ubiquitin-Specific Protease 13 (USP13)/Toll-like Receptor 4 (TLR4)/Myeloid Differentiation Primary Response Protein 88 (MYD88)/NF-κB pathway and the TLR4 ubiquitination levels were assessed using immunological quantification and biochemical methods. Relative to normal mice, OA mice exhibited decreased knee joint cartilage thickness and increased inflammatory damage. BH treatment reversed these effects. Furthermore, BH enhanced TLR4 ubiquitination. Estradiol acetate was identified as the metabolic component of BH that alleviates OA. Estradiol acetate and its subtype molecule β-Estradiol 3-acetate could bind to the USP13 protein. The β-Estradiol 3-acetate concentration-dependently decreased the elevated levels of USP13, TLR4, MYD88, p-p65/p65 in chondrocytes induced by LPS, while increasing the TLR4 ubiquitination. β-Estradiol 3-acetate reversed LPS-induced chondrocyte apoptosis and elevation of inflammatory factors. Moreover, USP13 overexpression abolished the protective effects of BH and β-Estradiol 3-acetate against LPS-induced chondrocytes. In Conclusion, the BH metabolite β-Estradiol 3-acetate promotes TLR4 ubiquitination to relieve inflammation and apoptosis in OA chondrocytes by inhibiting USP13.
研究领域:
药理学
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中医中药
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分子生物学
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风湿病学
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产品关联
DOI
PubMed
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
✓ 已验证
产品关联
DOI
高影响因子
LIFE SCIENCES
·
2021
·
IF 5.037
Mengyuan Fang,Wencui Wan,Qiuming Li,Weiwei Wan,Yang Long,Hongzhuo Liu,Xin Yang
Aim This study aimed to evaluate the effects of Asiatic acid (AA), a naturally occurring compound of pentacyclic triterpenoid, on the pathological processes of diabetic retinopathy (DR). Methods SD rats were induced to develop early DR by intraperitoneal injection of STZ (60 mg/kg). Four weeks after injection, the diabetic rats were orally administrated with 37.5 mg/kg or 75 mg/kg AA every day for four weeks. The integrity of blood-retinal barrier (BRB) was measured by Evans blue staining. The polarization of microglia was determined by real-time PCR, western blot, and ELISA assays. The inner BRB (iBRB) or outer BRB (oBRB) breakdown was induced in human retinal endothelial cells or APRE19 cells through co-culture with high glucose and LPS-stimulated microglia BV2 cells. The damage to the iBRB and oBRB was measured using transendothelial/transepithelial electrical resistance (TEER/TER) and FITC-conjugated dextran cell permeability assays. Key findings Results demonstrated that AA alleviated BRB breakdown, as evidenced by decreased protein expression of occludin, claudin-5, and ZO-1. Furthermore, AA treatment suppressed inflammation and M1 polarization, while it increased M2 polarization in the retina of DR rats. In vitro , the iBRB or oBRB breakdown was alleviated by AA. LPS-induced M1-polarization of BV2 cells under high glucose condition was also repressed through AA administration. Finally, we demonstrated that AA weakened the TLR4/MyD88/NF-κB p65 signaling pathway both in vivo and in vitro . Significance AA ameliorated early DR by regulating microglia polarization via the TLR4/MyD88/NF-κB p65 pathway. These data indicate that AA is a potential candidate for DR treatment.
研究领域:
药理学
·
眼科学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Yuanyuan Fu,Ting Wang,Xinyue Ge,Hong Wen,Yang Fei,Menghuan Li,Zhong Luo
Probiotics emerges as a promising option for ulcerative colitis (UC) treatment, but its application remains challenging due to insufficient colon-targeted delivery efficiency and survival against the inflammation-associated intestinal oxidative stress. To address these issues, here we report a supramolecular liposome-microgel complex (SLMC) incorporated with Bacillus subtilis spores (BSSs) and dexamethasone (DEX) for orally-deliverable probiotic UC therapy. Specifically, BSSs and cholesterols were conjugated with gelatin via diselenide ligation to prepare microgels, followed by supramolecular complexation with UC-targeted DEX-loaded liposome via microfluidic engineering. The orally-administered SLMC efficiently accumulated in UC-affected colonic sites to release BSSs and DEX. DEX elicited rapid anti-inflammatory effect to reduce ROS generation, which cooperated with the ROS consumption by spore germination and diselenide cleavage to orchestrate an anaerobic intestinal microenvironment, thus promoting Bacillus subtilis colonization to restore gut homeostasis and initiate anti-inflammatory microbiota-macrophage metabolic crosstalk. Indeed, in vivo analysis showed that the SLMC treatment markedly inhibited pro-inflammatory TLR4-NF-κB signaling activities in mucosal macrophages through localized DEX delivery and boosting tryptophan metabolite production, leading to robust and durable UC abolishment. This study offers a practical approach for improving UC treatment in the clinic.
研究领域:
生物医学工程
·
消化病学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
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