Advanced Healthcare Materials
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2024
·
IF 10
Xiali Yin,Yaohua Ke,Ying Liang,Shuxian Zhang,Ziqi Chen,Lixia Yu,Ming Jiang,Qin Liu,Xiaoping Gu
Chemotherapy is the cornerstone of triple-negative breast cancer. The poor effectiveness and severe neuropathic pain caused by it have a significant impact on the immune system. Studies confirmed that immune cells in the tumor microenvironment (TME), have critical roles in tumor immune regulation and prognosis. In this study, it is revealed that the painless administration of Esketamine, combined with Cisplatin (DDP), can exert an anti-tumor effect, which is further boosted by the hydrogel delivery system. It is also discovered that Esketamine combined with DDP co-loaded in Poloxamer Hydrogel (PDEH) induces local immunity by increasing mature Dendritic Cells (mDCs) and activated T cells in PDEH group while the regulatory T cells (Tregs) known as CD4 + CD25 + FoxP3 + decreased significantly. Finally, , CD8 + and CD4 + T cells in the spleen exhibited a significant increase, suggesting a lasting immune impact of PDEH. This study proposes that Esketamine can serve as a painless immune modulator, enhancing an anti-tumor effect while co-loaded in poloxamer hydrogel with DDP. Along with improving immune cells in the microenvironment, it can potentially alleviate anxiety and depression. With its outstanding bio-safety profile, it offers promising new possibilities for painless clinical therapy.
研究领域:
肿瘤学
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药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2026
·Vol. 21
·期 9
·e0358125
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IF 2.8
Jingwang Liu,Jiaxin Liu,Tianyi He,Penghui Zhang,Nan Zhao,Maozheng Wei,Yuxin Guan,Peng Liu,Shuang Zhao,Xiuli Wang
Tourniquet-associated lower limb ischemia-reperfusion can induce skeletal muscle inflammation, edema, and early functional impairment, in which autophagy dysregulation may be involved. The present study was designed to investigate the effects of esketamine (ESK) on skeletal muscle injury following lower limb ischemia-reperfusion in mice and its relationship with autophagy regulation. A mouse model of left hindlimb ischemia for 3 hours followed by 24 hours of reperfusion was established, and changes in hindlimb perfusion, functional outcomes, tissue injury, inflammatory response, and autophagy-related markers were examined after intervention with ESK alone or in combination with chloroquine phosphate (CQ). The results showed that ESK attenuated the abnormally elevated perfusion after reperfusion, improved motor performance and partial muscle contractile function, yet exerted limited effects on mechanical pain threshold and nerve stimulation-induced muscle contraction. Concurrently, ESK alleviated histological damage, edema, and sarcolemmal integrity disruption in the gastrocnemius muscle, reduced serum Tumor Necrosis Factor-alpha and Interleukin-6 levels, and downregulated the expression of several inflammation-related genes. With respect to autophagy, ESK increased the microtubule-associated protein 1 light chain 3 II/I ratio while decreasing sequestosome 1 levels and the phosphorylated mechanistic target of rapamycin/total mechanistic target of rapamycin ratio; these protective effects were partially abrogated by CQ. Collectively, these findings indicate that ESK mitigates acute-phase skeletal muscle injury and improves selected early functional outcomes after lower limb ischemia-reperfusion in mice, and that its protective actions may be associated with suppression of inflammation and modulation of autophagy.
✓ 已验证
DOI
高影响因子
Neuropsychiatric Disease and Treatment
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2025
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IF 2.9
Yueyi Zhang,Qianqian Cai,Lingshan Wang,Bei Zhang
Background & Aims Esketamine, a promising treatment for treatment-resistant depression, has shown potential advantages over traditional antidepressants. However, its mechanisms remain unclear. This study explores how esketamine alleviates depressive behaviors through activation of the BDNF/TrkB/PI3K/AKT signaling pathway.Methods Using a Chronic Unpredictable Mild Stress (CUMS) rat model, behavioral assays (Sucrose Preference Test, Morris Water Maze Test) and histological analyses (HE and Nissl’s staining) were performed. Esketamine (5 mg/kg) treatment was administered to evaluate its antidepressant effects, and the PI3K inhibitor, PI3K-IN-6, was used to investigate the role of the PI3K/AKT pathway in the underlying mechanism.Results Esketamine treatment improved depressive behaviors, enhanced neuronal structure, and reduced apoptosis and oxidative stress. These effects were linked to the activation of the BDNF/TrkB/PI3K/AKT pathway. PI3K-IN-6 reversed the effects, confirming the pathway’s involvement.Conclusion Esketamine alleviates depressive behaviors by activating the BDNF/TrkB/PI3K/AKT signaling pathway, reducing oxidative stress and inhibiting neuronal apoptosis. These findings highlight the therapeutic potential of esketamine in treating depression, particularly in cases where traditional treatments fail.
研究领域:
神经药理学
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精神病学
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分子生物学
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神经科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）