Frontiers in Immunology
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2025
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IF 5.9
Jikai He,Jiaqi Jia,Wenhao Qu,Shuyu Zhang,Keyu Fan,Runze Lin,Wei Zhao,Yan Niu,Yanqiang Huang,Lizhou Jia
Objective To analyze differences in gut microbiota composition, metabolites, and metabolic pathways between healthy individuals and colorectal cancer (CRC) patients, and to investigate the inhibitory effects of N-methylserotonin (NMS) produced by Bacteroides ovatus (B.o) from orange fiber on CRC progression and its underlying mechanisms. Methods (1) Fecal samples from CRC patients (n=26) and healthy controls (n=20) were collected for metagenomic sequencing and untargeted metabolomics analysis; (2) The ability of B.o to produce NMS from orange fiber was validated in vitro ; (3) A CRC mouse model was established using azoxymethane (AOM)/dextran sulfate sodium (DSS) induction, followed by evaluation of body weight, rectal bleeding, colorectal length, tumor number, and intestinal barrier function; (4) Network pharmacology, molecular docking, and western blot analysis were combined to verify the mechanism of action; (5) 16S rRNA sequencing was performed to analyze gut microbiota changes. Results (1) CRC patients showed significantly increased metabolic pathways including glycolysis, methane metabolism, beneficial amino acid degradation, and linoleic acid degradation, along with significantly decreased B.o abundance and NMS levels, which were positively correlated; (2) NMS significantly inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis; (3) Combined treatment with B.o and orange fiber or NMS alone reduced tumorigenesis and improved intestinal barrier function; (4) Mechanistic studies revealed that these effects could be mediated through downregulation of 5-hydroxytryptamine receptor 1D (HTR1D) expression and inhibition of the cAMP/PKA/IκBα/NF-κB pathway; (5) The treatments optimized gut microbiota structure and metabolite composition. Conclusion B.o and its metabolite NMS possibly inhibit CRC progression by modulating the HTR1D-mediated cAMP/PKA/NF-κB signaling pathway, while improving gut microbiota structure, providing a novel therapeutic target for CRC prevention and treatment.
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2025
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IF 3.1
Meng-Si Li,Kai Liu
IgA nephropathy (IgAN), the most common form of glomerulonephritis, is a major and growing public health issue. It results from intestinal barrier dysfunction that leads to mesangial deposition of pathogenic galactose-deficient IgA1 (Gd-IgA1) and renal inflammation. This study aimed to investigate the therapeutic effects and associated mechanisms of forsythiaside A on intestinal barrier injury in IgAN in animal models. Rats were treated with bovine serum albumin (BSA), carbon tetrachloride (CCl 4 ), and lipopolysaccharide (LPS) to induce IgAN, followed by intragastric administration of forsythiaside A once daily from weeks 15 to 20 after model establishment. Biochemical markers, including 24-h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal and intestinal tissue pathology, and levels of pro-inflammatory cytokines in the serum, kidney, and intestine, intestinal tight junction proteins, and TLR4/NF-κB pathway components were examined. The results showed that forsythiaside A decreased 24-h urinary protein, BUN, and SCr levels, alleviated renal damage, and attenuated glomerular and tubular lesions, collagen deposition, and glomerular IgA deposition in IgAN rats. Forsythiaside A treatment inhibited CD68-positive macrophage infiltration in renal tissues and downregulated serum and renal levels of IL-1β, IL-6, and TNF-α, while also alleviating intestinal barrier injury and intestinal inflammation, as shown by reduced levels of IL-1β, IL-6, and TNF-α and increased expression of the intestinal tight junction proteins occludin and ZO-1. Lastly, forsythiaside A treatment lowered serum LPS concentrations, as well as renal and intestinal levels of TLR4, p-NF-κB p65, and p-IκBα, and raised both renal and intestinal levels of IκBα. Collectively, forsythiaside A was found to ameliorate the progression of IgAN in rats by alleviating inflammation and intestinal barrier injury by suppression of TLR4/NF-κB signaling.
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JOURNAL OF ALLOYS AND COMPOUNDS
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2025
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IF 6.3
Yuyan Tang,Tingting Fan,Arslan Hameed,Yuanhang Ma,Wenxiang Sheng,Yawei Li,Ping Chen,Peng Li
To address the escalating global energy demand and advance sustainable hydrogen production, we report the rational design of a carbon-encapsulated La-doped Ni 2 P/NiSe heterojunction electrocatalyst on nickel foam (La-Ni 2 P/NiSe@C/NF) via synergistic La doping and interface engineering for enhanced urea oxidation reaction (UOR). La induces porous, wrinkled nanosheets, boosting surface area (11.89 m 2 g -1 ), enhancing active site exposure. The Ni 2 P/NiSe heterointerfaces generate built-in electric fields that accelerate interfacial charge transport. XPS, EXAFS, and in situ Raman confirm La doping modulates Ni 3+ electronic structure, thereby shifting the Ni²⁺/Ni³⁺ redox transition to lower potentials, thereby shifting the Ni 2+ /Ni 3+ redox transition to lower potentials. The La-Ni 2 P/NiSe@C/NF exhibits excellent UOR activity in an alkaline electrolyte, delivering a current density of 10 mA cm -2 at 1.296 V (vs. RHE). Remarkably, it achieves a low Tafel slope of 32.73 ± 0.73 mV dec -1 . These performance metrics surpass both control samples and state of the art benchmark materials. Moreover, a two-electrode electrolyzer assembled with La-Ni 2 P/NiSe@C/NF||Pt/C/NF exhibits exceptional 250 h stability at 50 mA cm -2 , underscoring the efficacy of rare-earth doping and heterointerface engineering for high-performance UOR.
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ENVIRONMENTAL POLLUTION
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2021
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IF 8.071
Jiaqi Xu,Qiuhui Qian,Min Xia,Xuedong Wang,Huili Wang
Trichlorocarban (TCC) is ubiquitously detected in environmental matrices, while there is a paucity of information regarding its systemic toxicity. In the present study, we observed that TCC exposure led to high embryo mortality, delayed hatching and yolk absorption, as well as increased malformations, such as closure of swim sac and yolk sac edema. Meanwhile, TCC affected the formation and branch of subintestinal veins (SIVs), intersegmental vessels and posterior cardinal veins. Especially, the SIVs were shrunk, and their branches were reduced or even broken along with reduced coverage area. TCC-induced oxidative stress and excessive apoptosis resulted from abnormal expression of the anti/pro-apoptotic genes. Significant reduction in the number and aggregation function of immune cells proved that TCC had prominent immunotoxicity to zebrafish. TCC-targeted TLR4 signaling pathway was demonstrated by abnormal expression of the marker genes ( tlr4 , MyD88 and nf-κb ) and release of the downstream inflammatory factors (TNF-α, IL-6, etc.). Inhibition of TLR4/MyD88/NF-κB pathway by an inhibitor (CA-4948) rescued the decreasing trend of the immune cells induced by TCC. Molecular docking results demonstrated that TCC could stably bind to TLR4 receptor to form hydrogen bonds and hydrophobic interactions with amino acids. Overall, these findings reveal the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish.
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Frontiers in Pharmacology
·
2018
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IF 3.831
Yang Junfa,Liu Qingxue,Cao Shiyang,Xu Tao,Li Xiaofeng,Zhou Dandan,Pan Linxin,Li Changyao,Huang Cheng,Meng Xiaoming,Zhang Lei,Wang Xiao
During the liver fibrosis recovery stage tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can effectively induce apoptosis of activated hepatic stellate cells (HSCs). Normal hepatic stellate cells are resistant to TRAIL cytotoxicity. Therefore, enhancing the sensitivity of TRAIL-induced apoptosis of HSCs may be useful to treat hepatic fibrogenesis. Here, we demonstrated that miR-145 and TRAIL were down-regulated in both liver fibrosis tissue samples and transforming growth factor-β1 induced HSCs, concomitant with increased the expression of ZEB2. In addition, we found that mimics-mediated over-expression of miR-145 led to resistance to the ZEB2 expression and up-regulation of the TRAIL-induced apoptosis after treatment of LX-2 cells with TRAIL. Furthermore, ZEB2-siRNA transfected LX-2 cells showed the increased sensitivity to TRAIL-induced apoptosis. Whereas, opposite results were obtained in miR-145-inhibitor group or ZEB2 plasmid group. Moreover, miR-145 regulated ZEB2 gene expression by specifically interacting with the 3′-UTR of ZEB2 mRNA to inhibit the expression of ZEB2. Further studies showed that the over-expression of ZEB2 could inhibit TRAIL-induced apoptosis via inhibiting nuclear factor-κB (NF-κB) signaling pathway in LX-2 cells. Collectively, our data suggest that up-regulation of miR-145 can down-regulate ZEB2 expression, consequently promoting TRAIL-induced apoptosis in LX-2 cells through NF-κB signaling pathway, which facilitates the resolution of liver fibrosis.
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AMERICAN JOURNAL OF CHINESE MEDICINE
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2023
·Vol. 51
·期 08
·2157-2173
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IF 5.7
Zhenfeng Liu,Wuming Zhou,Qingyang Liu,Zhirong Huan,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α ) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Zhou-Wei Wu,Xing-Rong Peng,Xiao-Cui Liu,Luan Wen,Xin-Yu Tao,Abdulbaset Al-Romaima,Ming-Yi Wu,Ming-Hua Qiu
Lepidium meyenii Walp., also known as the “Peruvian national treasure”, is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii . The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6- α -D-Glc, while branches feature T- α -L-Ara, 1,5- α -L-Ara, and T- α -D-Glc attached to the O -6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6- β -D-Gal, 1,3,6- β -D-Gal with a few 1,3- β -D-Glc p A-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3- β -D-Gal, T- β -D-Gal, T- α -L-Ara, 1,5- α -L-Ara, with trace amounts of 1,4- β -D-Glc and T- β -D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1 β , TNF- α , and IL-6 from RAW 264.7 cells at concentrations ranging from 50 μg/mL to 400 μg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB- α , p-IκB- α , p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.
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ACS Omega
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2024
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IF 3.7
Hao Xu,Ning Ning Guo,Chen Ying Zhu,Lin Yan Ye,Xing Yi Yan,Yong Qin Liu,Ze Yan Zhang,Guangji Zhang,Liaqat Hussain
Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
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Frontiers in Immunology
·
2025
·
IF 5.9
You Zhou,Kai Yang,Jian Wang,Ruijuan Guan,Wei Liu,Chaowei Wen,Liang Yuan,Tiange Zhang,Wei Feng,Yuanyuan Li,Jingyi Xu,Wenju Lu
Backgrounds: Exposure to fine particulate matter (PM2.5) triggers airway inflammation through the activation of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, contributing to the pathogenesis of various acute and chronic respiratory diseases. Mucin 1 (MUC1), a transmembrane glycoprotein highly expressed on airway epithelial cells, is known to modulate TLR-mediated inflammatory responses. However, the specific role and molecular mechanism by which MUC1 regulates PM2.5-induced airway inflammation remain inadequately understood.Methods: Lung injury models were established using Muc1+/+ and Muc1-/- rats via intranasal instillation of PM2.5. Histopathological changes and inflammatory responses were evaluated following treatment. In parallel, human bronchial epithelial cells (16HBE) were transfected with MUC1 overexpression and knockdown plasmids, along with corresponding controls. An IRAK4-specific inhibitor was employed to explore the mechanistic role of MUC1 in regulating the TLR4/IRAK4/NF-κB signaling cascade and associated pyroptosis.Results: PM2.5 exposure caused notable epithelial disruption, inflammatory infiltration, and submucosal fibrosis in Muc1-/- rats compared to Muc1+/+ controls. While TLR4 expression was not significantly altered, NF-κB and NLRP3 inflammasome activity were markedly elevated in Muc1-deficient rats. In 16HBE cells, MUC1 overexpression attenuated, whereas MUC1 knockdown exacerbated, PM2.5-induced activation of the IRAK4/NF-κB signaling axis and pyroptosis-related markers (IL-1β, IL-18, NLRP3, GSDMD). Furthermore, pharmacological inhibition of IRAK4 mitigated these effects, confirming the involvement of the IRAK4 pathway in MUC1-mediated protection.Conclusions: MUC1 is upregulated in airway epithelial cells upon PM2.5 exposure and serves as a key endogenous inhibitor of airway inflammation. It exerts its anti-inflammatory and anti-pyroptotic effects by suppressing IRAK4 phosphorylation, thereby modulating downstream NF-κB/NLRP3/GSDMD signaling. These findings highlight MUC1 as a potential therapeutic target for PM2.5-induced airway inflammatory diseases.
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JOURNAL OF FOOD BIOCHEMISTRY
·
2026
·Vol. 2026
·期 1
·8438287
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IF 2.3
Shiying Mai,Liyan Li,Yinfeng Tan,Minghai Fu,Junqing Zhang,Fang Zhang,Yonghui Li,Qi Wang,Yuhuang Wu
Background Lihuabidouyan Tablet is a compound Chinese herb preparation used for the treatment of respiratory diseases. As the main active ingredient in it, Ficus pumila ( F . pumila ) contains polysaccharides that exert unique biological activity. In this study, polysaccharides in F . pumila were extracted and purified, and the protective effect and mechanism of action of F . pumila polysaccharide 1-1 (FPP1-1) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice were discussed. Methods BALB/c mice were randomly divided into control, model, dexamethasone (DEX), and FPP-1-1 groups (50, 100, and 200 mg/kg), and the drug was administered by gavage for one week. Hematoxylin–eosin staining (H&E) and wet/dry ratio were used to evaluate lung injury and pulmonary edema. The ELISA was used to detect inflammatory factors. qRT-PCR was used to examine mRNA expression in tissues. Proteins related to inflammation were evaluated by western blotting. 16S rDNA sequencing was used to analyze the gut microbiota. Results FPP-1-1 significantly reduced lung injury in the ALI mice and significantly reduced levels of the proinflammatory factors interleukin (IL)-6 and tumor necrosis (TNF)- α and promoted the anti-inflammatory factor IL-10 in bronchoalveolar lavage fluid. FPP-1-1 inhibited the expression of phospho-ERK1/2, phospho-P38, and phospho-NF- κ B p65 proteins. FPP-1-1 also increased the diversity of the gut microbiota and increased the abundance of Lachnospiraceae in the ALI mice. Correlation analysis results showed that there was a significant correlation between the MAPK/NF- κ B pathway and inflammatory cytokines and gut microbiota in ALI mice. Conclusion The present study characterized the structure and molecular weight of a novel homogeneous polysaccharide, FPP-1-1, isolated from F. pumila . In addition, FPP-1-1 affected the expression of inflammatory factors by inhibiting the MAPK/NF- κ B pathway. FPP-1-1 also restored the diversity of gut microbiota and changed the relative abundance of key bacterial genera such as Lachnospiraceae and Alloprevotella , suggesting that the “gut–lung” axis may serve as a crucial pathway through which FPP-1-1 exerts its effect.
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NEUROSCIENCE LETTERS
·
2026
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IF 2.2
Wuwei Xu,Yanxin Xu,Chunyan Yao,Xianmei Fu,Xiaoling Liu,Jinping Fan,Kexue Wang,Yumeng Zhou,Yuefei Li,Ting Hu,Yan Sai,Peng Luo,Tongjian Cai
T-2 toxin is a widely distributed environmental mycotoxin that poses severe neurotoxic risks to humans and animals. Neuroinflammatory responses constitute a key mechanism underlying the neurotoxicity of T-2 toxin. However, its molecular mechanisms for inducing inflammatory responses in the nervous system remain incompletely understood. This study investigated the role of B-cell translocation gene 2 (BTG2) in T-2 toxin-induced microglial activation and evaluated the neuroprotective potential of resveratrol (Res). In vivo experiments demonstrated that exposure to T-2 toxin resulted in spatial learning, memory impairments and locomotor deficits in mice. These behavioral phenotypes were accompanied by neuroinflammation in the hippocampus and cerebral cortex, characterized by microglial activation and the upregulation of BTG2. Res pre-treatment effectively reversed these neurobehavioral deficits and suppressed the neuroinflammatory response. Mechanistic analyses revealed that Res considerably alleviated T-2 toxin-induced TLR4/MyD88/NF-κB pathway activation. In vitro studies using BV-2 microglial cells confirmed these findings. Notably, siRNA-mediated knockdown of BTG2 also abolished TLR4 pathway activation and subsequent cytokine expression induced by T-2 toxin, establishing BTG2 as a critical upstream regulator. Furthermore, RNA sequencing systematically verified that BTG2 regulates the immune response network, specifically targeting the TLR4 cascades. Collectively, these findings provide novel evidence that Res may target the BTG2-regulated TLR4/MyD88/NF-κB signal pathway to exert neuroprotection, providing a promising intervention option for reducing the environmental and health hazards associated with exposure to T-2 toxin
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Frontiers in Microbiology
·
2026
·
IF 5.8
Yidong Xu,Xinyi Li,Yaodong Miao,Xiaoxi Liu,Xiya Zang,Qinghao Meng,Ying Li,Fengwen Yang,Zhiguang Yuchi,Yiwen Wang
Objective Xuanfei Baidu decoction (XFBD), one of China’s recommended prescriptions for COVID-19, has demonstrated clinical efficacy in mitigating gastrointestinal inflammation associated with SARS-CoV-2 infection, yet its exact therapeutic mechanism remains incompletely understood, necessitating further in vivo investigation. In this study, we utilized a fruit fly ( Drosophila melanogaster ) model of intestinal inflammation to assess the therapeutic potential and underlying mechanisms of XFBD in ameliorating intestinal inflammation. Methods We induced intestinal inflammation in D. melanogaster by dextran sulfate sodium (DSS) administration. We examined XFBD’s protective effects on D. melanogaster ’s intestine and explored changes in the IMD and JNK-JAK/STAT signaling pathways. Furthermore, we analyzed the intestinal microbiota through 16S rRNA gene sequencing. Results XFBD effectively mitigated DSS-induced intestinal inflammation, leading to a significant extension of the flies’ lifespan. It enhanced the integrity of intestinal barrier while reducing reactive oxygen species (ROS) levels in intestine. Additionally, XFBD restored the disrupted intestinal microbiota by regulating immune homeostasis, notably inhibiting the IMD, Toll, and JNKJAK/STAT pathways. Furthermore, the reintroduction of symbiotic microbiota partially alleviated the DSS-induced dysregulation. Conclusion In conclusion, our study underscores the therapeutic potential of XFBD for intestinal inflammation, providing valuable insights into its key mechanisms and highlighting the pivotal role of symbiotic microbiota in anti-inflammatory responses and immune pathway regulation.
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