PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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2025
·Vol. 122
·期 34
·e2503779122
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IF 9.1
Changming Wang,Haiwang Ji,Hanwen Wang,Ziyun Chen,Lan Zhou,Yan Yang,Yucui Jiang,Guang Yu,Ling Jiang,Zongxiang Tang
Cancer-induced bone pain (CIBP) is a severely painful condition that profoundly impacts patients’ quality of life. However, the neuroimmune mechanisms underlying CIBP remain largely elusive. Substance P (SP), which is known to play a pivotal role in pain perception, became the focal point of our study. To this end, we adopted a comprehensive approach combining behavioral and physiological methods to investigate its role in neuroimmune interactions in CIBP. The results showed that SP released by dorsal root ganglion (DRG) neurons via exocytosis initiates CIBP, with its release peaking on the 14th day and correlating with pain behavior. Macrophages were found to infiltrate the DRGs and the sciatic nerves. Notably, in mice with CIBP, the population of macrophage type I was significantly augmented. Significantly, we found that the deletion of macrophages led to a notable alleviation of CIBP, while the blockade of the SP-neurokinin 1 receptor pathway effectively mitigated the infiltration of macrophages and alleviated CIBP. In the advanced phase, DRGs released C-C Motif Chemokine Ligand 3 and C-C Motif Chemokine Ligand 2 to recruit macrophages. A two-phase model for CIBP progression in mice was proposed, with SP-induced macrophage infiltration in the primary phase and chemokine-mediated macrophage recruitment in the advanced phase. Our investigation has unearthed a previously unrecognized mechanism governing the neuroimmune interaction in CIBP, which highlights a critical target for impeding the progression of this debilitating pain, potentially opening up broad avenues for the development of effective therapeutic interventions at different stages of CIBP with cancer development.
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高影响因子
Heliyon
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2023
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IF 4
Yanfeng Huang,Qing Lin,Xue Tan,Liangliang Jia,Hui Li,Zaishi Zhu,Changlong Fu,Lili Wang,Linlong Liu,Min Mao,Zhouping Yi,Dezun Ma,Xihai Li
Osteoarthritis (OA) is a common joint disease characterized by chronic pain, and the perception of pain is closely associated with brain function and neuropeptide regulation. Rehmannia is common plant herb with anti-inflammatory and analgesic properties that is used to treat OA. However, it is unclear whether Rehmannia alleviates OA-related pain via regulation of neuropeptides and brain function. We examined the pain relief regulatory pathway in OA after treatment with Rehmannia by verifying the therapeutic effect of Rehmannia alcohol extract in vivo and vitro and exploring of the potential mechanism underlying the analgesic effect of Rahmanian using functional magnetic resonance imaging and measuring neuropeptide secretion. Our results showed that Rehmanni a alcohol extract and the related active ingredient, Rehmannioside D , can delay cartilage degradation and alleviate inflammation in OA rats. The Rehmanni a alcohol extract can also relieve OA pain, reduce the secretion of calcitonin gene-related peptide (CGRP) and substance P (SP), and reverse the pathological changes in the cerebral cortex and hippocampus. Our research results demonstrate that Rehmannia alleviates OA pain by protecting cartilage, preventing the stimulation of inflammatory factors on neuropeptide secretion, and influencing the relevant functional areas of the brain.
研究领域:
药理学
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神经科学
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风湿病学
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中医
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高影响因子
CLINICAL AND EXPERIMENTAL ALLERGY
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2021
·Vol. 52
·期 1
·46-58
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IF 5.018
Nan Wang,Jue Wang,Yongjing Zhang,Shiling Hu,Tianxiao Zhang,Yuanyuan Wu,Xiuzhen Sun,Tao Zhang,Shuanying Yang,Langchong He
Background Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early-stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma. Objective We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma. Methods We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mouse serum. Results Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5 and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice. Conclusions & clinical relevance Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs. Graphical Here, we found that SP levels were increased in the serum samples of patients with asthma, which was independently associated with the risk of asthma. In mice model, SP induced lung peribronchial inflammation, fibrosis, and glycogen deposition, with high levels of Th2-related cytokines in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kit W-sh/W-sh mice, which indicated that SP induced Th2 lung inflammation in mice was dependent on MCs.
研究领域:
免疫学
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肺科学
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过敏学
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分子生物学
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高影响因子
Food Quality and Safety
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2024
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IF 3
Fu Hanyue,Fan Dancai,Wang Jin,Kou Ruixin,Wang Yuanyifei,Wu Yuekun,Wang Shuo
ObjectivesConstipation is a prevalent gastrointestinal issue, and the efficacy of probiotics in alleviating constipation has been well proved. This study aimed to investigate the impact of Bifidobacterium longum subsp. infantis NKU FB3-14 on loperamide- induced constipation by focusing on improving intestinal barrier function and modulating gut microbiota compositionMaterials and MethodsThe constipated model mice induced by loperamide were treated with NKU FB3-14, and the laxative effect was assessed based on the fecal water content, first black stool time and gastrointestinal transit rate. Gastrointestinal regulatory peptides in serum, intestinal neurotransmitter and inflammatory cytokines in colon tissues were measured using ELISA kits. Changes of gut microbiota composition were analyzed through 16S ribosomal DNA sequencing identification. Additionally, HPLC detection was performed to quantify short chain fatty acids levels in fecesResultsTreatment with NKU FB3-14 led to increase the fecal water content, shorten the first black stool time and improve small intestine transit rate. Motilin and substance-P significantly decreased in the model group, and only motilin increased in FB3-14 group; somatostatin and vasoactive intestinal peptide were decreased in model mice and both increased in FB3-14 group; 5-HT levels in the colon tissue were upregulated following NKU FB3-14 treatment. Histological examination revealed thinner colonic mucosa in the model group along with significant in TNF-α, IL-1β and IL-17 levels form the colon tissues which were all relieved by NKU FB 3-14 treatment. Furthermore, NKU FB3-14 intervention resulted in reduced abundance of Desulfobacterota and Desulfovibrio while increasing the abundance of Ruminococcaceae and Eubacterium; higher level of butyric acid was observed in fecesConclusionsIn summary, our findings demonstrated that NKU FB3-14 treatment significantly enhanced the intestinal motility, regulated the expression levels of gastrointestinal regulatory peptides, prevented damage to colonic barriers as well as ameliorated gut microbiota imbalance associated with loperamide-induced constipation.
研究领域:
胃肠病学
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微生物学
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药理学
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益生菌
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Tian Li,Mengmeng Hu,Cuihua Jiang,Dongjian Zhang,Meng Gao,Jianwei Xia,Mengqi Miao,Gaofeng Shi,Hui Li,Jian Zhang,Zhiqi Yin
Ethnopharmacological relevance Tiantian capsule (TTC), as a functional food, which consists of four herb medicines, including Aloe vera Burm.f. (25%), leaf juices, dried; Cucurbita moschata Duch. (25%), fructus, dried; Poria cocos (Schw.) Wolf. (12.5%), sclerotium, dried; Tremella fuciformis Berk. (12.5%), fruiting bodies, dried, and one extract xylooligosaccharides (25%) from Maize Cob by enzymolysis, has been commonly used in China to ameliorate constipation. Aim of the study The aim of the work is to elucidate the potential laxative mechanisms of TTC in loperamide-induced constipated rats. Materials and methods LC-MS/MS was employed for analyzing the TTC extract. The gastrointestinal transit was evaluated by X-ray. The H&E and Alcian-Blue stain were applied to determine the changes of goblet cells and mucus layer, respectively. Meanwhile, levels of neurotransmitters were evaluated by enzyme-linked immunosorbent assay. The protein expressions were also measured by immunohistochemistry and Western blot . Results Our results showed that TTC administration attenuated constipation responses in aspects of fecal pellets number, water content of feces, stomach emptying and gastrointestinal transit. Further investigations revealed that TTC treatment not only induced the recovery of neurotransmitters, such as motilin , substance P , somatostatin , endothelin and vasoactive intestinal peptide , but also up-regulated the expressions of c-kit and stem cell factor (SCF). Additionally, the number of goblet cells and thickness of the mucus layer were elevated, and the guanylate cyclase C-cGMP signal pathway was also up-regulated after TTC treatment. Conclusion Our findings demonstrated that the laxative effect of TTC in constipation rats is probably due to the regulation of bowel movement and intestinal fluid secretion.
研究领域:
药理学
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胃肠病学
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民族药理学
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高影响因子
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