IN VIVO
·
2024
·Vol. 38
·期 3
·1133-1142
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IF 1.8
LONGJIE XU,LILI HOU,CHUN CAO,XIAOHUA LI
Background/Aim: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. Materials and Methods: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. Results: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. Conclusion: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.
研究领域:
神经科学
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疼痛研究
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肿瘤学
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药理学
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DOI
PubMed
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2025
·Vol. 122
·期 34
·e2503779122
·
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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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2020
·
IF 7.097
Yanjuan Huang,Zhanghong Xiao,Zilin Guan,Zishan Zeng,Yifeng Shen,Xiaoyu Xu,Chunshun Zhao
The “vicious cycle” established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the “vicious cycle”, innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed. Herein, a bone-seeking moiety, alendronate (ALN), functionalized coordination polymer nanoparticles ( [email protected] ) co-delivering cisplatin prodrug (DSP) and antiresorptive agent zoledronate (ZOL) via Zn 2+ crosslinking for combination therapy was reported. The versatile [email protected] with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries, and possesses an excellent bone-seeking ability both in vitro and in vivo . Additionally, [email protected] could synergistically inhibit the proliferation of cancer cells, suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro . Importantly, it could preferentially accumulate in bone affected site, remarkably inhibit the proliferation of tumor cells, relieving bone pain, and significantly inhibit the activation of osteoclasts, protecting the bone from destruction in vivo , eventually leading to the breakdown of “vicious cycle” without inducing obvious systemic toxicity. This innovative nanoagent combines chemotherapy and osteolysis inhibition, exhibiting an inspiring strategy for effective treatment of bone metastasis.
研究领域:
肿瘤学
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药学
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纳米技术
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生物材料
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Yanbei Tu,Kai Wang,Yeer Liang,Xuejing Jia,Lili Wang,Jian-Bo Wan,Jianping Han,Chengwei He
Ethnopharmacological relevance The whole plant of Glycine tabacina (Labill.) Benth has been used as a traditional herbal medicine to treat rheumatism , ostealgia and nephritis in China. It is also one of the sources of the renowned native herbal medicine ‘I-Tiao-Gung’ in Taiwan. Aim of the study This study aimed to investigate the anti-arthritic effect of ethanol extract of G. tabacina (GTE) in a collagen-induced arthritis (CIA) rat model. Materials and methods The chemical profile of GTE was analyzed by HPLC-UV. The CIA was induced in male Wistar rats by intradermal injection of bovine type II collagen at tail root, back and ankle joints. The rats were orally administrated daily with GTE (1.11, 2.22 and 4.44 g dry weight of herb powder per kg body weight) from day 0 and continued for 30 days. Swelling volume and thickness of paw, arthritis index, X-radiographs and histopathological changes were examined to assess the severity of arthritis. Furthermore, the levels of pro-inflammatory cytokines, such as interleukin1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α), total superoxide dismutase (T-SOD) activity and malonaldehyde (MDA) level were measured to preliminarily explore the possible mechanisms. Results Oral administration of GTE significantly ameliorated the arthritic symptoms in CIA rat model, as indicated by the effects on paws swelling and arthritis index. X-radiographic analysis and histopathological examinations demonstrated that GTE effectively protected the bone and cartilage of joints from erosion, lesion and deformation. The efficacy of GTE treatment on CIA was comparable to that of indomethacin (positive drug). Besides, the overproduction of IL-1β, IL-6 and TNF-α was remarkably inhibited in the serum of all GTE treatment groups. The restoration of serum T-SOD activity and MDA level proved that GTE administration alleviated the oxidative stress in CIA rats. Conclusions GTE exhibited strong anti-CIA activity through inhibiting pro-inflammatory cytokines and oxidation in rats, suggesting its potential preventive and therapeutic effects on rheumatoid arthritis (RA).
研究领域:
药理学
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民族药理学
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
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