Antioxidants
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2024
·Vol. 13
·期 7
·803
·
IF 6
Zhen Shen,Yun-Dan Guo,Ming-Ze Tang,Ping Zhou,Yu-Xin Su,Hao-Ran Shen,Tao Li,Wei Jiang,Yan-Xing Han,Cai Tie,Jing-Jing Cui,Tian-Le Gao,Jian-Dong Jiang
Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investigation into the potentiation of pregabalin’s analgesic effects by dexborneol, a neuroprotective bicyclic monoterpenoid compound. We performed animal experiments where pain models were induced using two methods: peripheral nerve injury, involving axotomy and ligation of the tibial and common peroneal nerves, and incisional pain through a longitudinal incision in the hind paw, while employing a multifaceted methodology that integrates behavioral pharmacology, molecular biology, neuromorphology, and lipidomics to delve into the mechanisms behind this potentiation. Dexborneol was found to enhance pregabalin’s efficacy by promoting its transportation to the central nervous system, disrupting self-amplifying vicious cycles via the reduction of HMGB1 and ATP release, and exerting significant anti-oxidative effects through modulation of central lipid metabolism. This combination therapy not only boosted pregabalin’s analgesic property but also notably decreased its side effects. Moreover, this therapeutic cocktail exceeded basic pain relief, effectively reducing neuroinflammation and glial cell activation—key factors contributing to persistent and chronic pain. This study paves the way for more tolerable and effective analgesic options, highlighting the potential of dexborneol as an adjuvant to pregabalin therapy.
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Jingsong Lu,Yupei Wang,Xiaohan Gao,Ying Li,Neema Ufurahi Pambe,Abdul Fahad,Zeping Jin,zhijun He,Zhenhu Guo,Wensheng Xie,Shi Wang,Xiaodan Sun,Xiumei Wang,Jing Yu,Shenglei Che,Guifeng Zhang,Yen Wei,Lingyun Zhao
Enlightened by the great success of drug repurposing strategy in pharmaceutic industries, in the current study, material repurposing was proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinical was explored in anti-cancer treatment. Except for the abnormal iron metabolic characteristics of tumors that serving as potential targets for CIP-based cancer therapy under repurposing paradigm, the efficacy of CIP as catalyst in Fenton reaction, activator for dihydroartemisinin (DHA) and thus increase the chemo-sensitivity of tumors, as well as the potent agent for NIR-II photothermal therapy (PTT) was fully evaluated by an injectable alginate hydrogel form. The CIP-ALG gel could cause rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further on, such photothermal-ablation would lead to ATP release significantly and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Material repurposing could thus be confirmed by our pioneering trial and the CIP-ALG meditated NT/PTT/immunotherapy would provide new choice of strategy for safe and efficient tumor therapy.
研究领域:
肿瘤学
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材料科学
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生物医学工程
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药学
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
Science Signaling
·
2020
·Vol. 13
·期 646
·
IF 6.467
Xiao-Wei Gu,Zi-Cong Chen,Zhen-Shan Yang,Yan Yang,Ya-Ping Yan,Yue-Fang Liu,Ji-Min Pan,Ren-Wei Su,Zeng-Ming Yang
Embryo implantation involves a sterile inflammatory reaction that is required for the invasion of the blastocyst into the decidua. Adenosine triphosphate (ATP) released from stressed or injured cells acts as an important signaling molecule to regulate many key physiological events, including sterile inflammation. We found that the amount of ATP in the uterine luminal fluid of mice increased during the peri-implantation period, and this depended on the presence of an embryo. We further showed that the release of ATP from receptive epithelial cells was likely stimulated by lactate released from the blastocyst through connexin hemichannels. The ATP receptor P2y2 was present on uterine epithelial cells during the preimplantation period and increased in the stromal cells during the time at which decidualization began. Pharmacological inhibition of P2y2 compromised decidualization and implantation. ATP-P2y2 signaling stimulated the phosphorylation of Stat3 in uterine luminal epithelial cells and the expression of early growth response 1 ( Egr1 ) and prostaglandin-endoperoxide synthase 2 ( Ptgs2, also known as Cox-2 ), all of which are required for decidualization and/or implantation, in stromal cells. Short exposure to high concentrations of ATP promoted decidualization of primary stromal cells, but longer exposures or lower ATP concentrations did not. The expression of genes encoding ATP-degrading ectonucleotidases increased in the decidua during the peri-implantation period, suggesting that they may limit the duration of the ATP signal. Together, our results indicate that the blastocyst-induced release of ATP from uterine epithelial cells during the peri-implantation period may be important for the initiation of stromal cell decidualization.
研究领域:
生殖生物学
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发育生物学
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细胞信号转导
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分子胚胎学
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免疫学（无菌性炎症）
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）