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Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus. 人参皂苷Rg1通过抑制下丘脑外侧的奥曲肽神经元和下丘脑室旁核的促肾上腺皮质激素释放激素神经元,促进非快速眼动睡眠。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-06 DOI: 10.1016/j.joim.2024.11.001
Yi-Yuan Wang, Yi Wu, Ke-Wei Yu, Hong-Yu Xie, Yi Gui, Chang-Rui Chen, Nian-Hong Wang

Objective: This study investigates the sleep-modulating effects of ginsenoside Rg1 (Rg1, C42H72O14), a key bioactive component of ginseng, and elucidates its underlying mechanisms.

Methods: C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to 100 mg/kg. Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles. Further, orexin neurons in the lateral hypothalamus (LH) and corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) were ablated using viral vector surgery and electrode embedding. The excitability of LHorexin and PVHCRH neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-Fos) expression.

Results: Rg1 (12.5-100 mg/kg) augmented the duration of non-rapid eye movement (NREM) sleep phases, while reducing the duration of wakefulness, in a dose dependent manner. The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time. We found that these sleep-promoting effects were weakened in the LHorexin and PVHCRH neuron ablation groups, and disappeared in the orexin and CRH double-ablation group. Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.

Conclusion: Rg1 increases the duration of NREM sleep, underscoring the essential roles of LHorexin and PVHCRH neurons in facilitating the sleep-promoting effects of Rg1. Please cite this article as: Wang YY, Wu Y, Yu KW, Xie HY, Gui Y, Chen CR, Wang NH. Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus. J Integr Med . 2024; Epub ahead of print.

研究目的本研究探讨了人参皂苷 Rg1(Rg1,C42H72O14)(人参的一种主要生物活性成分)的睡眠调节作用,并阐明了其潜在机制:方法:给 C57BL/6J 小鼠腹腔注射 12.5 至 100 mg/kg 剂量的 Rg1。通过监测大脑和肌肉的电活动,评估睡眠参数以确定每个睡眠阶段的平均持续时间。此外,还使用病毒载体手术和电极嵌入法消融了下丘脑外侧(LH)的奥曲肽神经元和下丘脑室旁核(PVH)的促肾上腺皮质激素释放激素(CRH)神经元。通过测量细胞Finkel-Biskis-Jinkins小鼠骨肉瘤病毒癌基因同源物(c-Fos)的表达,评估了LHorexin和PVHCRH神经元的兴奋性:结果:Rg1(12.5-100 毫克/千克)以剂量依赖的方式延长了非快速眼动(NREM)睡眠阶段的持续时间,同时缩短了觉醒的持续时间。从觉醒到非快速眼动睡眠的潜伏期缩短表明睡眠启动时间加快。我们发现,这些促进睡眠的作用在 LHorexin 和 PVHCR 神经元消融组中减弱,而在 orexin 和 CRH 双消融组中消失。LH和PVH中c-Fos蛋白表达的减少证实了Rg1通过抑制orexin和CRH神经元来促进NREM睡眠:结论:Rg1能延长NREM睡眠时间,强调了LHorexin和PVHCRH神经元在促进Rg1的睡眠效应中的重要作用。本文引用如前Wang YY, Wu Y, Yu KW, Xie HY, Gui Y, Chen CR, Wang NH.人参皂苷Rg1通过抑制下丘脑外侧的奥曲肽神经元和下丘脑室旁核的促肾上腺皮质激素释放激素神经元促进非快速眼动睡眠。J Integr Med . 2024; Epub ahead of print.
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引用次数: 0
A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. Scutellaria barbata D. Don和Scleromitrion diffusum(Willd.)
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-18 DOI: 10.1016/j.joim.2024.10.001
Zhen Wang, Min Liu, Guang-Xing Li, Liu Zhang, Kai-Yue Ding, Si-Qi Li, Bing-Qing Gao, Peng Chen, Hyok-Chol Choe, Lun-Yue Xia, Yu-Tong Yang, Yi Liu, Xue Sui, Jun-Nan Ma, Lin Zhang

Objective: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization.

Methods: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells.

Results: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4.

Conclusion: SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; Epub ahead of print.

目的:尽管黄芩(Scutellaria barbata D. Don)和白花蛇舌草(Scleromitrion diffusum (Willd.) R.J. Wang)(SB-SD)是公认的中药组合,常用于治疗卵巢癌,但人们对其药理机制了解甚少。本研究通过多组学方法研究 SB-SD 对人类卵巢癌 A2780 细胞的抗肿瘤特性和潜在机制,为临床应用建立药理基础:方法:在热回流提取SB-SD过程中使用了不同的质量比和试剂。采用细胞计数试剂盒 8 方法评估了 SB-SD 提取物对 A2780 细胞增殖的抑制作用。斑马鱼肿瘤植入模型用于评估 SB-SD 提取物对体内肿瘤生长和转移的影响。转录组学和蛋白质组学用于研究不同浓度的 SB-SD 提取物处理 A2780 细胞后生物通路的改变。研究测定了细胞周期、细胞凋亡、细胞内游离铁浓度、细胞内活性氧(ROS)浓度、丙二醛(MDA)和线粒体膜电位。利用实时定量反转录聚合酶链反应和 Western 印迹技术研究了血红素分解和铁蛋白吞噬对 SB-SD 提取物诱导的 A2780 细胞铁变态反应的影响:SB-SD的70%乙醇提取物(质量比为4:1)能显著抑制A2780细胞的增殖,半数最大抑制浓度为660 μg/mL,且呈浓度和时间依赖性。此外,它还能在斑马鱼肿瘤植入模型中有效抑制肿瘤的生长和转移。SB-SD 提取物能诱导 A2780 细胞中游离铁、ROS、MDA 的积累和线粒体损伤。其机制可能涉及铁蛋白吞噬相关基因微管相关蛋白 1 轻链 3、自体吞噬相关基因 5 和核受体辅激活因子 4 的表达上调:SB-SD提取物能有效抑制卵巢癌的体内外发展。其作用机制包括通过促进血红素分解和噬铁蛋白诱导铁变态反应。这对草药有望成为卵巢癌治疗的潜在疗法,并可与常规治疗相结合,改善卵巢癌患者的治疗效果。本文引用如前:Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy.J Integr Med.2024; Epub ahead of print.
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引用次数: 0
Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment. 解毒方是一种复方中药,它通过抑制缺氧微环境中肿瘤外泌体的释放来抑制肝细胞癌的转移。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-18 DOI: 10.1016/j.joim.2024.10.002
Wen-Tao Jia, Shuang Xiang, Jin-Bo Zhang, Jia-Ying Yuan, Yu-Qian Wang, Shu-Fang Liang, Wan-Fu Lin, Xiao-Feng Zhai, Yan Shang, Chang-Quan Ling, Bin-Bin Cheng

Objective: Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown.

Methods: Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR.

Results: JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment.

Conclusion: JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; Epub ahead of print.

目的肿瘤外泌体(TDEs)在细胞间通信中发挥着关键作用。肿瘤微环境缺氧会促进 TDEs 的分泌,加速肿瘤转移。传统中药方剂解毒方(JR)在预防肝细胞癌(HCC)转移方面具有显著疗效。然而,其潜在机制仍不为人知:方法:通过动物实验研究 JR 的预防转移作用。方法:通过动物实验研究 JR 的预防转移作用,并通过生物信息学分析和体外试验探索 JR 的潜在靶点和活性成分。使用纳米颗粒追踪分析(NTA)和免疫印迹(WB)对TDEs进行评估。收集来自正常或缺氧 HCC 细胞(H-TDEs)的外泌体,建立转移前小鼠模型。胃内注射 JR 以评估其预防转移的作用。进行WB和溶酶体染色以研究JR对溶酶体功能和自噬的影响。通过生物信息学分析、WB、NTA和免疫荧光染色来确定JR的活性成分和潜在靶点:结果:JR能有效抑制皮下肿瘤促进的肺转移龛发展和肿瘤转移。它抑制了缺氧条件下肿瘤细胞外泌体的释放。JR处理可促进溶酶体酸化和抑制分泌性自噬,而缺氧条件下肿瘤细胞的分泌性自噬失调。槲皮素被鉴定为 JR 的活性成分,表皮生长因子受体(EGFR)被鉴定为潜在靶点。槲皮素抑制了表皮生长因子受体的磷酸化,并促进了转录因子 EB(TFEB)的核转位。缺氧受损的溶酶体功能得到恢复,分泌性自噬在槲皮素的作用下得到缓解:结论:JR通过抑制缺氧刺激的外泌体释放、恢复溶酶体功能和抑制分泌性自噬来抑制HCC转移。槲皮素是 JR 的关键成分,通过表皮生长因子受体-TFEB 信号转导调节 TDE 的释放。我们的研究为通过靶向H-TDE分泌延缓肿瘤转移提供了一种潜在的策略。本文引用如前Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB.解毒方通过表皮生长因子受体-TFEB信号通路抑制肿瘤外泌体在缺氧微环境中的释放,从而抑制肝细胞癌转移。J Integr Med.2024; Epub ahead of print.
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引用次数: 0
Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. 人参皂苷Rh1通过糖皮质激素受体调节肝细胞癌的免疫微环境
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-30 DOI: 10.1016/j.joim.2024.09.004
Xiong-Hui Wang, Ya-Lan Fu, Yan-Nan Xu, Peng-Cheng Zhang, Tian-Xiao Zheng, Chang-Quan Ling, Ying-Lu Feng

Objective: Ginsenoside Rh1 (G-Rh1) has been confirmed to inhibit the growth of breast cancer and colon cancer, but its therapeutic effect on hepatocellular carcinoma (HCC) is unclear. This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism.

Methods: Bioinformatics methods were used to analyze glucocorticoid receptor (GR) expression and the tumor microenvironment in HCC tissues from HCC patients. The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice. Additionally, the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry, the GR and major histocompatibility complex class-I (MHC-I) expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting, and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell (DC) maturation and CD8+ T cell activation.

Results: GR expression was upregulated in HCC tissues, and high GR expression was associated with a worsened immune microenvironment. In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells, while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice. Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment, thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8+ T cells, mature DCs, and MHC-I-positive cells. MHC-I was upregulated by G-Rh1 via GR suppression. Moreover, overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells, as well as the maturation of DCs and the activation of CD8+ T cells.

Conclusion: G-Rh1 can regulate the immune microenvironment of HCC by targeting GR, thus increasing the antitumor effect of lenvatinib. Please cite this article as: Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL. Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. J Integr Med. 2024; Epub ahead of print.

研究目的人参皂苷Rh1(G-Rh1)已被证实可抑制乳腺癌和结肠癌的生长,但其对肝细胞癌(HCC)的治疗效果尚不明确。本研究探讨了 G-Rh1 对 HCC 的治疗作用及其机制:方法:采用生物信息学方法分析糖皮质激素受体(GR)的表达以及HCC患者HCC组织中的肿瘤微环境。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑法在体外研究了 G-Rh1 对 HCC 细胞的影响。在 C57BL/6J 和裸鼠皮下移植模型中,研究了 G-Rh1 的体内治疗效果。此外,还利用流式细胞术分析了肿瘤中浸润免疫细胞的比例,利用Western印迹分析了G-Rh1处理后HCC细胞的GR和主要组织相容性复合体Ⅰ类(MHC-Ⅰ)表达,并将G-Rh1处理后的Hepa1-6细胞与骨髓树突状细胞和B3Z T细胞共培养,进一步分析了G-Rh1诱导树突状细胞(DC)成熟和CD8+ T细胞活化的能力。结果HCC组织中GR表达上调,GR高表达与免疫微环境恶化有关。体外研究表明,G-Rh1 对 HCC 细胞的增殖无明显影响;体内研究表明,G-Rh1 对 C57BL/6J 小鼠有抗肿瘤作用,但对裸鼠无作用。进一步的研究发现,G-Rh1能改善免疫抑制性肿瘤微环境,从而通过增加CD8+ T细胞、成熟DC和MHC-I阳性细胞的浸润来增强来伐替尼的抗肿瘤作用。G-Rh1通过GR抑制作用上调了MHC-I。此外,GR的过表达可消除G-Rh1介导的对Huh7细胞中MHC-I表达的促进作用,以及对DCs成熟和CD8+ T细胞活化的促进作用:结论:G-Rh1可通过靶向GR调节HCC的免疫微环境,从而增强来伐替尼的抗肿瘤作用。本文引用如前Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL.人参皂苷Rh1通过糖皮质激素受体调节肝细胞癌的免疫微环境J Integr Med.2024; Epub ahead of print.
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引用次数: 0
A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. 黄芩苷及其葡萄糖醛酸衍生物黄芩苷的抗病毒作用综述。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-21 DOI: 10.1016/j.joim.2024.09.003
Xin-Yang Liu, Wei Xie, He-Yang Zhou, Hui-Qing Zhang, Yong-Sheng Jin

Natural product-based antiviral candidates have received significant attention. However, there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance. Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi. They have proven to be effective against a broad range of viruses by directly killing virus particles, protecting infected cells, and targeting viral antigens on their surface, among other mechanisms. As natural products, they both possess the advantage of lower toxicity, enhanced therapeutic efficacy, and even antagonistic effects against drug-resistant viral strains. Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds, demonstrating their antiviral properties. However, to date, no review on the antiviral effects of baicalein and baicalin has been published. This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms. The aim is to provide a basis for the rational development and utilization of baicalein and baicalin, as well as to promote antiviral drug research. Please cite this article as: Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. J Integr Med. 2024; Epub ahead of print.

以天然产物为基础的候选抗病毒药物受到了极大关注。然而,抗病毒领域缺乏足够的研究来有效对抗耐药性模式。黄芩苷及其葡萄糖醛酸衍生物黄芩素是从黄芩(Scutellaria baicalensis Georgi)中提取的两种主要成分。事实证明,它们通过直接杀死病毒颗粒、保护受感染细胞、靶向病毒表面的抗原等机制,对多种病毒有效。作为天然产品,它们都具有毒性低、疗效强的优点,甚至对耐药性病毒株有拮抗作用。黄芩素和黄芩苷作为强效药源支架具有广阔的发展前景,显示了它们的抗病毒特性。然而,迄今为止还没有关于黄芩苷和黄芩素抗病毒作用的综述。本综述总结了黄芩苷和黄芩素在体外和体内对各种类型病毒的抗病毒作用的最新研究进展,重点关注其剂量和潜在机制。目的是为合理开发和利用黄芩苷和黄芩素提供依据,并促进抗病毒药物的研究。本文引用如前:Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS.黄芩苷及其葡萄糖醛酸衍生物黄芩苷的抗病毒作用综述。J Integr Med.2024; Epub ahead of print.
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引用次数: 0
Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. 辅助性非药物措施对改善严重 COVID-19 患者呼吸道症状的有效性和安全性:多中心随机对照试验。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-17 DOI: 10.1016/j.joim.2024.09.002
Xuan Yin, Zhu Jin, Feng Li, Li Huang, Yan-Mei Hu, Bo-Chang Zhu, Zu-Qing Wang, Xi-Ying Li, Jian-Ping Li, Lixing Lao, Yi-Qun Mi, Shi-Fen Xu
<p><strong>Background: </strong>The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear.</p><p><strong>Objectives: </strong>To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19.</p><p><strong>Design, setting, participants and interventions: </strong>This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days.</p><p><strong>Main outcome measures: </strong>The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO<sub>2</sub>) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO<sub>2</sub> and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO<sub>2</sub>, the duration of prone positioning, and adverse events were recorded as well.</p><p><strong>Results: </strong>Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO<sub>2</sub> above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO<sub>2</sub> was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95%CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness.</p><p><strong>Conclusion: </strong>TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO<sub>2</sub> and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory
背景:2022 年末,冠状病毒病 2019(COVID-19)感染的爆发给公共医疗保健带来了巨大的威胁和负担。针灸、拔罐、艾灸等中医非药物疗法是我国常用的辅助治疗手段,但其效果尚不明确:观察中医非药物疗法在改善重症 COVID-19 患者呼吸功能和症状方面的临床效果:本研究为多中心、评估者盲法、随机对照试验。COVID-19住院患者被随机分配到治疗组或对照组。治疗组接受个体化的中医非药物措施并结合俯卧位通气,而对照组仅接受连续 5 天的俯卧位通气:主要结果指标:5 天干预结束时,血氧饱和度(SpO2)得到改善的患者比例,以及患者呼吸频率的变化。次要结果指标包括 SpO2 的变化和自制呼吸症状量表的总分。此外,还记录了SpO2连续3天上升的改善率、俯卧位持续时间和不良事件:在纳入意向治疗分析的 198 名患者中,159 人(80.3%)在第 5 天完成了所有评估,39 人(19.7%)退出了研究。干预结束时,治疗组有 71 名(91%)患者的 SpO2 超过了 93%,而对照组有 61 名(75.3%)达到了这一水平。干预组中 SpO2 有所改善的患者比例明显更高(平均差 [MD] = 15.7;95% 置信区间 [CI]:4.4, 27.1;95% 置信区间 [CI]:4.4, 27.1):4.4, 27.1; P = 0.008).与基线相比,两组患者在接受日常治疗后,呼吸频率均有显著下降,但组间无统计学差异(P 均≥ 0.05)。与对照组相比,治疗组患者的呼吸相关症状评分在治疗第 3 天后降低(MD = -1.7; 95%CI: -2.8, -0.5;P=0.008)。两组患者的总分也逐渐下降。干预期间发生了31起不良事件,2名患者因病情恶化转入重症监护室:结论:中医非药物疗法结合俯卧位能有效治疗重症 COVID-19 患者。结论:中医非药物疗法联合俯卧位能有效治疗重症 COVID-19 患者,与单纯俯卧位相比,联合疗法能明显提高 SpO2,改善症状评分,从而改善患者的呼吸功能,帮助患者康复。然而,两组患者的改善率并无差异:试验注册:中国临床试验注册中心(ChiCTR2300068319)。本文引用如前:Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF.非药物辅助措施改善重症 COVID-19 患者呼吸道症状的有效性和安全性:多中心随机对照试验J Integr Med.2024; Epub ahead of print.
{"title":"Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial.","authors":"Xuan Yin, Zhu Jin, Feng Li, Li Huang, Yan-Mei Hu, Bo-Chang Zhu, Zu-Qing Wang, Xi-Ying Li, Jian-Ping Li, Lixing Lao, Yi-Qun Mi, Shi-Fen Xu","doi":"10.1016/j.joim.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.joim.2024.09.002","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, participants and interventions: &lt;/strong&gt;This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO&lt;sub&gt;2&lt;/sub&gt;) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO&lt;sub&gt;2&lt;/sub&gt; and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO&lt;sub&gt;2&lt;/sub&gt;, the duration of prone positioning, and adverse events were recorded as well.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO&lt;sub&gt;2&lt;/sub&gt; above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO&lt;sub&gt;2&lt;/sub&gt; was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95%CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO&lt;sub&gt;2&lt;/sub&gt; and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory ","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. 叶黄素通过 p53 途径减少氧化应激和细胞凋亡,从而防止心肌缺血/再灌注损伤。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-07 DOI: 10.1016/j.joim.2024.09.001
Pan Zhai, Xiao-Hu Ouyang, Meng-Ling Yang, Lan Lin, Jun-Yi Li, Yi-Ming Li, Xiang Cheng, Rui Zhu, De-Sheng Hu

Objective: Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion therapy. This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.

Methods: Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery, and administered luteolin. The myocardial infarct size, myocardial enzyme levels, and cardiac function were measured. Latent targets and signaling pathways were screened using network pharmacology and molecular docking. Then, proteins related to the p53 signaling pathway, apoptosis and oxidative stress were measured. Hypoxia/reoxygenation (HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro. In addition, a p53 agonist and an inhibitor were used to investigate the mechanism.

Results: Luteolin reduced the myocardial infarcted size and myocardial enzymes, and restored cardiac function in MIRI mice. Network pharmacology identified p53 as a hub target. The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties. Additionally, luteolin halted the activation of p53, and prevented both apoptosis and oxidative stress in myocardial tissue in vivo. Furthermore, luteolin inhibited cell apoptosis, JC-1 monomer formation, and reactive oxygen species elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin-α demonstrated a similar therapeutic effect in the MIRI mice.

Conclusion: Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway. Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; Epub ahead of print.Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; Epub ahead of print.

目的:心肌缺血再灌注损伤(MIRI)是心脏再灌注疗法取得成功的障碍:心肌缺血再灌注损伤(MIRI)是心脏再灌注治疗成功的一个障碍。本研究探讨了叶黄素是否能通过调节 p53 信号通路减轻 MIRI:方法:对模型小鼠进行左前降支冠状动脉临时手术结扎,并注射叶黄素。测量心肌梗死面积、心肌酶水平和心功能。利用网络药理学和分子对接筛选了潜在靶点和信号通路。然后,测量了与 p53 信号通路、细胞凋亡和氧化应激有关的蛋白质。缺氧/再氧合(HR)诱导的 HL1 细胞被用来验证叶黄素在体外的作用。此外,还使用了一种 p53 激动剂和一种抑制剂来研究其机制:结果:木犀草素缩小了 MIRI 小鼠的心肌梗死面积,降低了心肌酶的含量,恢复了其心脏功能。网络药理学确定 p53 为中心靶点。生物信息学分析表明,木犀草素具有抗凋亡和抗氧化特性。此外,木犀草素还能阻止 p53 的活化,并防止体内心肌组织的凋亡和氧化应激。此外,叶黄素还能抑制体外 HR 诱导的 HL1 细胞的细胞凋亡、JC-1 单体形成和活性氧的升高。最后,在 MIRI 小鼠模型中,p53 激动剂 NSC319726 下调了叶黄素的保护特性,而叶黄素和 p53 抑制剂 pifithrin-α 在 MIRI 小鼠中也表现出了类似的治疗效果:结论:木犀草素可有效治疗MIRI,并可通过靶向p53信号通路调节细胞凋亡和氧化应激,从而改善心肌损伤。本文引用如前Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS.木犀草素通过p53通路降低氧化应激和细胞凋亡保护心肌缺血再灌注损伤J Integr Med.2024; Epub ahead of print.本文引用如前:Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS.木犀草素通过p53通路降低氧化应激和细胞凋亡保护心肌缺血再灌注损伤J Integr Med.2024; Epub ahead of print.
{"title":"Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.","authors":"Pan Zhai, Xiao-Hu Ouyang, Meng-Ling Yang, Lan Lin, Jun-Yi Li, Yi-Ming Li, Xiang Cheng, Rui Zhu, De-Sheng Hu","doi":"10.1016/j.joim.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.joim.2024.09.001","url":null,"abstract":"<p><strong>Objective: </strong>Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion therapy. This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.</p><p><strong>Methods: </strong>Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery, and administered luteolin. The myocardial infarct size, myocardial enzyme levels, and cardiac function were measured. Latent targets and signaling pathways were screened using network pharmacology and molecular docking. Then, proteins related to the p53 signaling pathway, apoptosis and oxidative stress were measured. Hypoxia/reoxygenation (HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro. In addition, a p53 agonist and an inhibitor were used to investigate the mechanism.</p><p><strong>Results: </strong>Luteolin reduced the myocardial infarcted size and myocardial enzymes, and restored cardiac function in MIRI mice. Network pharmacology identified p53 as a hub target. The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties. Additionally, luteolin halted the activation of p53, and prevented both apoptosis and oxidative stress in myocardial tissue in vivo. Furthermore, luteolin inhibited cell apoptosis, JC-1 monomer formation, and reactive oxygen species elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin-α demonstrated a similar therapeutic effect in the MIRI mice.</p><p><strong>Conclusion: </strong>Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway. Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; Epub ahead of print.Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Delphi study for developing a checklist of adverse events associated with acupotomy 为制定穴位切开术相关不良事件核对表而进行的德尔菲研究。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-01 DOI: 10.1016/j.joim.2024.08.003
Hyungsun Jun , Haebeom Lee , Sang-Hoon Yoon , Chan-Young Kwon , Damin Jeon , Jun-Hwan Lee , Jungtae Leem

Background

Acupotomy, a more invasive procedure than acupuncture, involves the use of a thicker needle with an integrated knife at the tip, necessitating safety research. We aimed to define relevant adverse events (AEs) and create a standardized form of the ACUPOtomy-related AEs CHECKlist (ACUPOCHECK).

Methods

Before conducting the Delphi process, a systematic review and pilot prospective study were conducted to gather information on previously reported AEs. Using these data, pilot versions of the ACUPOCHECK and Delphi questionnaires were developed. The Delphi questionnaire involved selecting types of AE for inclusion, establishing separate criteria for acupotomy-related AEs, and achieving a consensus on AE assessment. Thirteen Korean doctors with experience in acupotomy or AE research were recruited to participate in each Delphi round. Consensus was considered to have been reached if the critical value for the content validity ratio met or exceeded 0.538.

Results

The final ACUPOCHECK was developed using four rounds of the Delphi method and one face-to-face consensus meeting. It included 12 local AEs (pain, hemorrhage, bruise, hematoma, edema, pruritus, rash, infection, nerve damage, dysesthesia, movement impairment, and pneumothorax) and 14 systemic AEs (disease aggravation, needle fatigue, sleepiness, procedural nausea, procedural vomiting, procedural headache, procedural dizziness, sweating, procedural shock, syncope, dyspnea, procedural pain, sleep disorder, and postprocedural infection). Separate criteria were established for pain, hemorrhage and bruising: pain was defined as pain that occurrs during daily activities and persists for longer than 72 h, hemorrhage as bleeding that continues for ≥ 3 min despite pressure application, and bruising as having a bruise with a diameter of ≥ 3 cm. Open-ended descriptions were allowed for AEs not covered by the checklist, and severity and causality were assessed using the Common Terminology Criteria for Adverse Events and modified World Health Organization-Uppsala Monitoring Center criteria.

Conclusion

ACUPOCHECK provides a standardization framework that can help research on traditional practices as well as new tools and techniques that are more invasive and may cause more severe AEs. Subsequent studies will use ACUPOCHECK to develop rational safety guidelines for acupotomy techniques.
Please cite this article as: Jun H, Lee H, Yoon SH, Kwon CY, Jeon D, Lee JH, Leem J. Delphi study for developing a checklist of adverse events associated with acupotomy. J Integr Med. 2024; 22(5): 579–587.
背景:穴位切开术是一种比针灸更具侵入性的治疗方法,它需要使用一根更粗的针,针尖上还集成了一把刀,因此有必要进行安全性研究。我们的目标是定义相关不良事件(AEs),并创建一个标准化的针灸相关不良事件清单(ACUPOCHECK):在进行德尔菲过程之前,我们进行了系统回顾和试点前瞻性研究,以收集以前报告的 AEs 信息。利用这些数据,开发了 ACUPOCHECK 和德尔菲问卷的试验版本。德尔菲问卷调查包括选择纳入的 AE 类型、制定穴位切除术相关 AE 的单独标准以及就 AE 评估达成共识。每轮德尔菲问卷调查都招募了 13 名具有穴位切开术或 AE 研究经验的韩国医生参与。如果内容效度比临界值达到或超过 0.538,则认为已达成共识:最终的 ACUPOCHECK 是通过四轮德尔菲法和一次面对面的共识会议制定的。它包括 12 种局部 AE(疼痛、出血、瘀伤、血肿、水肿、瘙痒、皮疹、感染、神经损伤、感觉障碍、运动障碍和气胸)和 14 种全身 AE(疾病加重、针刺疲劳、嗜睡、术中恶心、术中呕吐、术中头痛、术中头晕、出汗、术中休克、晕厥、呼吸困难、术中疼痛、睡眠障碍和术后感染)。对疼痛、出血和瘀伤制定了不同的标准:疼痛是指在日常活动中出现的疼痛,且持续时间超过 72 小时;出血是指按压后出血仍持续≥ 3 分钟;瘀伤是指瘀伤直径≥ 3 厘米。对于检查表未涵盖的不良反应,允许进行开放式描述,并采用不良反应通用术语标准和世界卫生组织-乌普萨拉监测中心的修订标准评估严重程度和因果关系:ACUPOCHECK 提供了一个标准化框架,有助于对传统做法以及更具侵入性且可能导致更严重 AE 的新工具和技术进行研究。后续研究将利用 ACUPOCHECK 为穴位切开术制定合理的安全指南。本文引用如前:Jun H, Lee H, Yoon SH, Kwon CY, Jeon D, Lee JH, Leem J. Delphi study for developing a checklist of adverse events associated with acupotomy.J Integr Med.2024; Epub ahead of print.
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引用次数: 0
Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer’s disease by regulating hippocampal mitochondrial dynamics 电针通过调节海马线粒体动力学激活AMPKα1,从而改善早期阿尔茨海默病APP/PS1小鼠模型的学习和记忆。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-01 DOI: 10.1016/j.joim.2024.08.002
Wei-wei Jia , Hua-wei Lin , Min-guang Yang , Ya-ling Dai , Yan-yi Ding , Wen-shan Xu , Si-nuo Wang , Ya-jun Cao , Sheng-xiang Liang , Zhi-fu Wang , Cong Chen , Wei-lin Liu

Objective

Studies have shown that electroacupuncture (EA) can alleviate cognitive impairments from Alzheimer’s disease (AD) by regulating the expression of adenosine monophosphate-activated protein kinase (AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial dynamics.

Methods

The four-month-old transgenic mice with amyloid precursor protein (APP)/presenilin 1 (PS1) and AMPKα1-subunit conditional knockout (AMPKα1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition, chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 mice.

Results

Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway increased pathological amyloid-β (Aβ) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway, specifically by reducing pathological Aβ deposition, normalizing energy metabolism, protecting the structure and function of mitochondria, increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout.

Conclusion

The regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.
Please cite this article as: Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL. Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer’s disease by regulating hippocampal mitochondrial dynamics. J Integr Med. 2024; 22(5): 588–599.
研究目的研究表明,电针(EA)可通过调节单磷酸腺苷激活蛋白激酶(AMPK)的表达,缓解阿尔茨海默病(AD)引起的认知功能障碍,但其具体机制仍有待阐明。因此,本研究从线粒体动力学的角度探讨了EA改善认知功能的潜在机制:实验采用四个月大的淀粉样前体蛋白(APP)/淀粉样前体蛋白1(PS1)和AMPKα1亚基条件性敲除(AMPKα1-cKO)转基因小鼠。为了评估EA处理对认知功能的影响,实验采用了T迷宫和莫里斯水迷宫。此外,还采用了化学交换饱和转移、硫黄素染色、透射电子显微镜、线粒体膜电位和Western印迹等方法来研究EA对APP/PS1小鼠影响的潜在机制:结果:APP/PS1小鼠和AMPKα1-cKO小鼠均表现出线粒体动力学功能障碍,并伴有学习和记忆障碍。AMPK/过氧化物酶体增殖激活受体-γ辅助激活剂-1α(PGC-1α)通路的失活增加了病理性淀粉样蛋白-β(Aβ)沉积,加剧了线粒体动力学功能障碍。此外,EA通过激活AMPK/PGC-1α通路,特别是通过减少病理性Aβ沉积、使能量代谢正常化、保护线粒体的结构和功能、提高线粒体融合蛋白的水平以及下调裂变蛋白的表达,来挽救APP/PS1小鼠的学习和记忆缺陷。然而,AMPKα1基因敲除阻碍了EA对APP/PS1小鼠认知能力的治疗效果:结论:通过AMPK/PGC-1α途径调节海马线粒体动力学和减少Aβ沉积是EA改善APP/PS1小鼠认知障碍的关键。本文引用如前Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL.电针通过调节海马线粒体动力学激活 AMPKα1 以改善早期阿尔茨海默病 APP/PS1 小鼠模型的学习记忆能力J Integr Med.2024; Epub ahead of print.
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引用次数: 0
Unlocking the potential: How acupuncture reshapes the liver-centered lipid metabolism pattern to fight obesity 释放潜能:针灸如何重塑以肝为中心的脂质代谢模式以对抗肥胖。
IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-01 DOI: 10.1016/j.joim.2024.08.004
Shu-rui Yang , Li Chen , Dan Luo , Ya-yuan Wang , Feng-xia Liang
Obesity, a widespread global health issue, is frequently linked to disrupted lipid metabolism, resulting in excessive accumulation of adipose tissue and associated health complications. Acupuncture, a traditional Chinese medical modality, has exhibited potential as a viable intervention for addressing obesity. The underlying mechanism proposed involves the stimulation of specific acupoints to exert a regulatory influence on hepatic function. The liver has a central role in lipid metabolism, including processes such as lipid synthesis, storage and distribution. Acupuncture is believed to enhance the liver’s efficiency in processing lipids, thereby reducing lipid accumulation and improving metabolic functions. Research indicates that acupuncture can influence the expression of certain genes and proteins involved in lipid metabolism in the liver. This includes upregulating genes that promote lipid breakdown and oxidation, and downregulating those involved in lipid synthesis. Additionally, acupuncture has been shown to improve insulin sensitivity, which is crucial for the regulation of lipid metabolism. Furthermore, the potential anti-inflammatory effects of acupuncture may play a significant role in its efficacy for the treatment of obesity. The presence of chronic inflammation has been strongly associated with metabolic disorders such as obesity. Through its ability to mitigate inflammation, acupuncture can potentially aid in the restoration of lipid metabolism and the reduction of body weight. Moreover, the amelioration of hepatic oxidative stress represents another mechanism by which acupuncture may contribute to the reduction of lipid deposition. Notably, the liver, being the primary site of lipid metabolism, maintains communication with various organs including the brain, adipose tissue, skeletal muscle and intestines. This perspective opens new avenues for the treatment of obesity, emphasizing the importance of holistic approaches in managing complex metabolic disorders.
Please cite this article as: Yang SR, Chen L, Luo D, Wang YY, Liang FX. Unlocking the potential: How acupuncture reshapes the liver-centered lipid metabolism pattern to fight obesity. J Integr Med. 2024; 22(5): 523–532.
肥胖症是全球普遍存在的健康问题,往往与脂质代谢紊乱有关,导致脂肪组织过度堆积,并引发相关的健康并发症。针灸作为一种传统的中医疗法,已显示出作为一种可行的干预措施来解决肥胖问题的潜力。所提出的基本机制包括刺激特定穴位对肝功能产生调节作用。肝脏在脂质代谢中起着核心作用,包括脂质合成、储存和分配等过程。针灸被认为可以提高肝脏处理脂质的效率,从而减少脂质堆积,改善代谢功能。研究表明,针灸可以影响肝脏中参与脂质代谢的某些基因和蛋白质的表达。这包括上调促进脂质分解和氧化的基因,下调参与脂质合成的基因。此外,针灸还能提高胰岛素的敏感性,而胰岛素对脂质代谢的调节至关重要。此外,针灸潜在的抗炎作用也可能在其治疗肥胖症的疗效中发挥重要作用。慢性炎症的存在与肥胖等代谢性疾病密切相关。通过缓解炎症,针灸可能有助于恢复脂质代谢和减轻体重。此外,改善肝脏氧化应激也是针灸有助于减少脂质沉积的另一种机制。值得注意的是,肝脏作为脂质代谢的主要场所,与大脑、脂肪组织、骨骼肌和肠道等多个器官保持着联系。这一观点为肥胖症的治疗开辟了新途径,强调了综合方法在控制复杂代谢紊乱中的重要性。本文引用如前:Yang SR, Chen L, Luo D, Wang YY, Liang FX.释放潜能:针灸如何重塑以肝为中心的脂质代谢模式以对抗肥胖?J Integr Med.2024; Epub ahead of print.
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Journal of Integrative Medicine-Jim
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