POULTRY SCIENCE
·
2026
·
IF 4.5
Dan Shao,Longqing Hu,Wei Guo,Jinglong Chen,Xuming Guo,Hong Yao
This study aimed to investigate the protective effect and mechanism of dietary dimethylglycine (DMG) on jejunal injury in yellow-feathered broilers subjected to cyclic heat stress (HS). A total of 180 35-day-old male yellow-feathered broilers were randomly allocated into 3 groups: the thermoneutral condition with basal diet group (CON), the cycle heat stress with basal diet group (HS, 32-35°C), and the cycle heat stress with 0.1% DMG in basal diet group (HS_DMG, 32-35°C). The experiment included a 7-day heating period followed by a 14-day cyclic heat stress period. Growth performance, rectal temperature, jejunal morphology and ultrastructure, inflammatory cytokine levels, and protein expression related to the TLR4/NF-κB pathway and MUC2 were evaluated. Additionally, primary chicken jejunal epithelial cells were isolated and exposed to heat stress with or without DMG pretreatment to validate in vivo findings. Results showed that heat stress significantly increased rectal temperature ( P < 0.05), had a tendency to reduce body weight (BW, P = 0.058) and average daily gain (ADG, P = 0.050), and increase the feed-to-gain ratio (F/G, P = 0.053). Histologically, HS caused epithelial shedding, reduced villus height and villus height/crypt depth, and induced microvilli damage and mitochondrial swelling, all of which were attenuated by DMG supplementation. Heat stress also elevated jejunal mucosa levels of IL-6, IL-8, IL-1 β , and TNF- α ( P < 0.05), while DMG reduced IL-6, IL-8, and TNF- α ( P < 0.05). Immunohistochemistry and western blotting revealed that HS decreased MUC2 expression and increased TLR4 and p-NF-κB-p65 protein levels ( P < 0.05), whereas DMG reversed these changes ( P < 0.05). In vitro, DMG pretreatment alleviated HS-induced reduction in inflammatory cytokine release, and alterations in TLR4, NF-κB, and MUC2 protein expression. In conclusion, dietary DMG supplementation alleviates cyclic heat stress-induced jejunal injury in yellow-feathered broilers by suppressing the TLR4/NF-κB signaling pathway and restoring MUC2 expression.
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BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Cheng Cao,Mubin Sun,Jiabao Li,Zhenyu Yuan,Yuwei Gu,Yufan Shao,Lisheng Wang,Xiaohua Jin,Yijie Cheng,Bo Fan
Urate transporter 1 (URAT1, encoded by SLC22A12 ) is a key mediator of renal urate reabsorption and an important pharmacological target for urate-related disorders. Sodium butyrate (BuNa), a gut microbiota derived short-chain fatty acid, has been implicated in host metabolic regulation, but its role in renal urate transport remains unclear. Here, using molecular docking, cellular thermal shift assays, immunoprecipitation-mass spectrometry and multi-omics analyses, we identified free fatty acid receptor 2 (FFAR2) as a direct target of BuNa in renal proximal tubular HK2 cells . BuNa binding upregulated FFAR2 and promoted URAT1 expression and urate uptake via an FFAR2-dependent pathway. Mechanistically, BuNa/FFAR2 signaling acts via GNAQ to activate PLCβ, generating diacylglycerol and engaging a PKC-dependent p38 MAPK/ELK1 cascade that upregulates arrestin beta 2 (ARRB2). ARRB2 directly binds to IκB, preventing its phosphorylation-dependent degradation, thereby stabilizing IκB and inhibiting NF-κB nuclear translocation. Within the SLC22A12 promoter, NF-κB (RELA/p50) and hepatocyte nuclear factor 1 beta (HNF1β) compete for overlapping binding sites. By blocking NF-κB nuclear entry, BuNa relieves this competition, permitting HNF1β-driven SLC22A12 transcription. Thus, BuNa enhances URAT1-mediated urate reabsorption in HK2 cells via an FFAR2/GNAQ/p38 MAPK/ELK1/ARRB2 axis that stabilizes IκB, suppresses NF-κB, and relieves the competitive binding between NF-κB and HNF1β on the SLC22A12 promoter. These findings establish a previously unrecognized gut microbiota–kidney axis linking microbial BuNa to renal urate homeostasis through a novel transcriptional regulatory circuit.
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BIOLOGICAL TRACE ELEMENT RESEARCH
·
2026
·
IF 4.3
Yang Wenyan,Ma Lu,Hu Ting,Zhang Lei,Wu Kewei,Chen Hualin,Zhang Dandan,Luo Peng
Geochemical fluoride pollution is a global public health issue affecting a wide range and large population. The major health hazard from long-term fluoride exposure is skeletal fluorosis, a highly disabling and irreversible bone damage disease with no effective early interventions available to date. Given reactive oxygen species (ROS) accumulation is a key event in fluoride-induced bone damage, we established a sodium fluoride-exposed rat model. During the phase when fluoride induced ROS accumulation and mild bone damage in rat bone tissue, we administered Rosa roxburghii Tratt juice (RRTJ)—a natural food-medicinal homologous plant with antioxidant properties—to explore its intervention effect and potential mechanism against fluoride-induced bone damage. Results showed RRTJ inhibited fluoride-induced decreases in bone mineral density and trabecular number in male rats. Since enhanced bone resorption mediated by osteoclast overactivation is the initiating link of these fluoride-induced pathological changes, this study further found RRTJ suppressed fluoride-induced increases in osteoclast activity in male rat bone tissue, specifically reducing osteoclast numbers in bone tissue and lowering serum levels of bone resorption markers CTX and TRAP-5b. This effect is achieved by RRTJ scavenging fluoride-induced ROS accumulation in bone tissue, restoring ROS/TNF-α/NF-κB pathway homeostasis, and thereby inhibiting the overexpression of osteoclast activation-related genes tartrate-resistant acid phosphatase and cathepsin K. In conclusion, this study confirms RRT inhibits fluoride exposure-induced bone damage in male rats by regulating ROS/TNF-α/NF-κB pathway homeostasis. These findings provide new perspectives on the mechanism of fluoride-induced bone damage and, more importantly, reveal a potential novel intervention strategy.
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FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
·
2022
·Vol. 61
·期 1
·34-46
·
IF 1.49
Lili Ji Xiaojing Shi Gaopin Wang Huiping Wu Zhansheng Hu
Introduction. Acute lung injury (ALI) is a major cause of death in sepsis patients. The Six-transmembrane protein of prostate 2 (STAMP2) is a key regulator of inflammation, while its role in septic ALI remains unclear. Material and methods. Male C57BL/6 mice were subjected to cecal ligation puncture (CLP) to induce experimental sepsis whereas lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used as the models of septic ALI in vivo and in vitro , respectively. Overexpression of STAMP2 in mouse lungs and RAW264.7 cells was performed with an adenoviral vector. We measured histological lung injury, lung wet/dry weight (W/D) ratio, and pulmonary myeloperoxidase (MPO) activity to assess lung injury extent. Cell counts in bronchoalveolar lavage fluid (BALF) were measured using Giemsa staining. The concentration of inflammatory factors was detected by enzyme-linked immunosorbent assay. The polarization of macrophages was evaluated by inducible nitric oxide synthase (iNOS) and F4/80 staining. The activation of cell apoptosis and NF-κB pathway was evaluated using Western blot, TUNEL staining, immunofluorescence, and immunohistochemistry. Results. Overexpression of STAMP2 alleviated CLP-induced lung injury of mice with decreased W/D ratio of the lung, and MPO activity in lung tissue. STAMP2 overexpression reduced the lung infiltration of inflammatory cells, and the levels of TNF-a, IL-6, and macrophage chemoattractant protein-1 (MCP-1) in BALF. Overexpressed STAMP2 inhibited macrophage M1 polarization in lung tissues as indicated by F4/80 and iNOS stainings in lung tissue. STAMP2 overexpression inhibited RAW 264.7 cell apoptosis by increasing Bcl-2 and decreasing Bax and cleaved-caspase 3 expression. Besides, STAMP2 overexpression suppressed nuclear factor κB (NF-κB) p65 pathway activation, as evidenced by reduced phosphorylation of IκBα, and phosphorylation and translocation of NF-κB p65. In vitro study further proved that STAMP2 overexpression suppressed the NF-κB pathway (IκBα/p65) in macrophages and decreased macrophage M1 polarization and M1-associated inflammatory factor production (TNF-a, IL-6, and MCP-1). Conclusions. Our study for the first time demonstrated that STAMP2 might be able to reduce inflammation in sepsis-induced ALI by inhibiting macrophage M1 polarization through repressing NF-κB signaling activation.
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FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Lei Diao,Wenjie Liu,Yawei Xu,Bin Zhang,Lingnan Meng,Rui Yin,Huijie Chen
Deoxynivalenol (DON) is one of the most common sources of fungal toxins in fish feed, posing a significant risk to the immune and reproductive systems of fish. Microalgal astaxanthin (MIA), a potent antioxidant derived from microalgae , confers multifarious advantages upon piscine organisms, notably encompassing its anti-inflammatory and antioxidant prowess. Herein, we investigated the potential of MIA in ameliorating the immunotoxicity of DON on carp (Cyprinus carpio L.) based on spleen lymphocytes treated with DON (1.5 ng/ml) and/or MIA (96 μM). Firstly, CCK8 results showed that DON resulted in excessive death of spleen lymphocytes. Secondly, spleen lymphocytes treated with DON had a higher proportion of pyroptosis , and the mRNA and protein levels of pyroptosis (NLRP3, IL-1β and ASC) in spleen lymphocytes were increased. Thirdly, the relative red fluorescence intensity of JC-1 and DCFH-DA showed decreased mitochondrial membrane potential and increased ROS in spleen lymphocytes treated with DON. Mitochondrial ATP, DNA and NADPH/NADP + analysis revealed decreased mitochondrial ATP, DNA and NADPH/NADP + levels in DON-treated lymphocytes, corroborating the association between DON exposure and elevated intracellular ATP, DNA and NADPH/NADP + in lymphocytes. DON exposure resulted in the downregulation of mitophagy-related genes and proteins (PINK1, Parkin and LC3) in lymphocytes. Notably, these effects were counteracted by treatment with MIA. Furthermore, DON led to the elevated secretion of inflammatory factors (TNF-α, IL-4 and IFN-γ), thereby inducing immune dysfunction in spleen lymphocytes. Encouragingly, MIA treatment effectively mitigated the immunotoxic effects induced by DON, demonstrating its potential in ameliorating pyroptosis, mitochondrial dysfunction and mitophagy impairment via regulating the mtROS-NF-κB axis in lymphocytes. This study sheds light on safeguarding farmed fish against agrobiological threats posed by DON, highlighting the valuable applications of MIA in aquaculture.
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Li Sinai,Liu Hongxu,Li Yue,Qin Xiaomei,Li Mengjie,Shang Juju,Xing Wenlong,Gong Yanbing,Liu Weihong,Zhou Mingxue
Background: Heart failure (HF) is the end stage of ischemic cardiovascular diseases; nonetheless, safe and effective therapeutic agents for HF are still lacking, and their discovery remains challenging. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a hospital preparation of traditional Chinese herbal, effectively protected ischemic injury in cardiovascular diseases. However, its therapeutic effects and possible mechanisms on HF remain unclear.Methods: A zebrafish HF model treated with verapamil was developed to assess the therapeutic effect of SYDC on HF zebrafish. Zebrafish were administered with SYDC and digoxin (positive control) by direct soaking. After drug treatment, zebrafish were randomly assigned to the visual observation and image acquisition using a Zebralab Blood Flow System. The reactive oxygen species (ROS), MDA, and SOD levels were determined by fluorescence signal detection, TBA, and WST-8 methods. RT-PCR determined the mRNA expressions of Caspase-3, Caspase-1, Bcl-2, Bax, IL-1β, NF-κB, and TNF-α.Results: SYDC significantly inhibited the levels of heart dilatation and venous congestion and markedly increased the levels of cardiac output, blood flow dynamics, and heart rates in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Moreover, SYDC also significantly decreased the levels of MDA and ROS and increased the level of SOD in HF zebrafish. The RT-PCR results revealed that SYDC decreased the expression of Caspase-1, Caspase-3, Bax, IL-1β, NF-κB, and TNF-α but increased the expression of Bcl-2 in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001).Conclusions: SYDC improved the heart function in verapamil-induced HF zebrafish and alleviated inflammation and apoptosis by inhibiting the ROS-mediated NF-κB pathway.
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Cancer Cell International
·
2021
·Vol. 21
·期 1
·1-14
·
IF 5.722
Li Chunyang,Yang Shuangqing,Ma Huaqing,Ruan Mengjia,Fang Luyan,Cheng Jing
Background Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells.Methods The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated.Results We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways.Conclusion sTaken together, ICA could be a potential supplementary agent for cervical cancer treatment.
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Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Li Ying-Qi,Chen Yi,Jiang Si-Qi,Shi Yuan-Yuan,Jiang Xiao-Li,Wu Shan-Shan,Zhou Ping,Wang Hui-Ying,Li Ping,Li Fei
Alzheimer’s disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a computational network model was established to identify the driving targets of ACT and predict its mechanism by integrating multiple available databases. The AlCl3-induced AD model in zebrafish larvae was successfully constituted to demonstrate the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. The NF-κB and AMPK pathways were further confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques, and molecular docking. The research provided an infusive mechanism of ACT and revealed the connection between metabolism and microglia polarization from the perspective of mitochondrial function. More importantly, it provided a systematic and comprehensive approach for the discovery of drug targets, including the changes in genes, metabolites, and proteins.
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Evidence-based Complementary and Alternative Medicine
·
2021
·
IF 2.63
Xin Mao,Shuyin Gu,Huiting Sang,Yilu Ye,Jingyan Li,Yunxia Teng,Feiyu Zhang,Qinhai Ma,Ping Jiang,Zifeng Yang,Weizhong Huang,Shuwen Liu
Background. Luofushan-Baicao Oil (LBO) is an essential oil-rich traditional Chinese medicine (TCM) formula that is commonly used to treat cold, cough, headache, sore throat, swelling, and pain. However, the anti-influenza activities of LBO and the underlying mechanism remain to be investigated. Methods. The in vitro anti-influenza activity of LBO was tested with methyl thiazolyl tetrazolium (MTT) and plaque assays. The effects of LBO on the expressions of viral nucleoprotein and cytokines were evaluated. In the polyinosinic-polycytidylic acid- (Poly I: C-) induced inflammation model, the influences of LBO on the expression of cytokines and the activation of NF-κB P65 (P65) and interferon regulatory factor 3 (IRF3) were tested. After influenza A virus (IVA) infection, mice were administered with LBO for 5 days. The lung index, histopathologic change, the expression of viral protein, P65, and IRF3 in the lung tissue were measured. The levels of proinflammatory cytokines in serum were examined. Results. In vitro, LBO could significantly inhibit the infection of IVA, decrease the formation of plaques, and reduce the expression of viral nucleoprotein and cytokines. LBO could also effectively downregulate the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and interferon-β and the activation of P65 and IRF3 in Poly I:C-treated cells. In the IVA-infected mice model, inhalation of LBO with atomizer could decrease the lung index, alleviate the pathological injury in the lung tissue, and reduce the serum levels of IL-1β and IL-6. LBO could significantly downregulate the expression of viral protein (nucleoprotein, PB2, and matrix 2 ion channel) and the phosphorylation of P65 and IRF3 in the lungs of mice. Conclusion. The therapeutic effects of LBO on treating influenza might result from the regulation of the immune response of IVA infection. LBO can be developed as an alternative therapeutic agent for influenza prevention.
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Biomaterials Science
·
2019
·Vol. 8
·期 1
·201-211
·
IF 5.251
Shuli Man,Miao Li,Jin Zhou,Haiyue Wang,Jinyan Zhang,Long Ma
Fe3O4 magnetic nanoparticles (MNPs), as one of the most intensively researched NPs, have a range of applications in cancer treatments. In current research, we have focused on the influences of MNPs on cancer cells. We chose polyethyleneimine (PEI) coated MNPs (PEI-MNPs) as a model and they are colloidally stable in biological media. It can be proved that PEI-MNPs result in autophagy induction via mTOR-Akt-p70S6 K and ATG7 signaling pathways. For the first time, we have reported that PEI-MNPs activate both NF-κB and TGF-β signaling, two key pro-inflammatory pathways, in cancer cells. More significantly, we have found that autophagy induction and NF-κB and TGF-β activation can be efficiently suppressed through the inhibition of PEI-MNP dependent reactive oxygen species (ROS) over-production. ROS are deemed as a ‘double edge sword’ for cancer cells, owing to the cancer-suppressing and cancer-promoting actions. Our findings would be useful for designing MNPs induced ROS anti-cancer strategies or diminishing long-term toxic effects.
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Shanshan Li,Xuedie Gu,Muyue Zhang,Qihang Jiang,Tong Xu
Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n -acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.
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Foods
·
2025
·Vol. 14
·期 4
·619
·
IF 5.1
Kaijie Shang,Zhiheng Zhao,Hua Chen,Xiaonan Bian,Xianquan Zhong,Xiaoping Hu,Xue Lin,Lu Wang
The consumption of wampee has traditionally been utilized to alleviate gastrointestinal inflammation and associated disorders; however, its exact mechanism has remained unknown. The aim of this study was to elucidate the therapeutic efficacy and underlying mechanism of wampee polyphenol extract (WPE) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). The findings revealed that WPE alleviated diverse symptoms of UC, regulated various inflammatory cytokines, and effectively protected the colon tissue structure and barrier integrity, thereby inhibiting LPS translocation. Moreover, WPE restored the richness and diversity of gut microbiota and optimized its structure at the phylum and genus levels, causing a notable improvement in short- chain fatty acid (SCFA) metabolism, particularly acetic acid, propionic acid, and butyric acid. Consequently, WPE was demonstrated to effectively suppress the LPS-induced TLR4-p38 MAPK/NF-κB signaling pathway by modulating gut microbiota and SCFA metabolism. These findings provided a theoretical basis for the use of wampee as a potential functional natural food for UC.
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