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Analyzing mechanisms of Qing Fei Bao Yuan Decoction granules in treating COPD based on LC-MS, network pharmacology and in vivo methods 基于LC-MS、网络药理学和活体方法分析清热保元颗粒治疗慢性阻塞性肺疾病的机制
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1016/j.jtcme.2024.04.005
Amei Tang, Yang Liu, Guoqiang Guan, Tong Hao, Feng-Di Cao
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引用次数: 0
Pulsatilla saponin inhibits the proliferation of keratinocytes and ameliorates imiquimod-induced psoriasis through the NF-κB and STAT3 signaling pathways 白头翁皂苷通过 NF-κB 和 STAT3 信号通路抑制角朊细胞增殖并改善咪喹莫特诱导的银屑病
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1016/j.jtcme.2024.04.001
Jilang Li, Haixin Qiu, Siyuan Li, Shan Han, Yuming He, Jiangcheng He, Xiang Gao, Jingjing Li, Jianfang Feng, Shilin Yang, Renyikun Yuan, Hongwei Gao
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引用次数: 0
A proteasome-dependent inhibition of SIRT-1 by the resveratrol analogue 4,4′-dihydroxy-trans-stilbene 白藜芦醇类似物 4,4′-二羟基-反式-二苯乙烯对蛋白酶体 SIRT-1 的依赖性抑制作用
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-08 DOI: 10.1016/j.jtcme.2024.03.001

Background and aim

Resveratrol (RSV), is a stilbene-based compound exerting wide biological properties. Its analogue 4,4′-dihydroxy-trans-stilbene (DHS) has shown improved bioavailability and antiproliferative activity in vitro and in vivo. One of the hypotheses on how resveratrol works is based on SIRT1 activation. Since their strict structural similarities, we have explored a potential interaction between DHS and SIRT1, in comparison with the parental molecule.

Experimental procedure

Timing of incubation and concentrations of DHS have been determined using MTT assay in normal human lung fibroblasts. Untreated, DHS- or RSV-treated cells were harvested and analysed by Western Blotting or RT-PCR, in order to evaluate SIRT1 levels/activity and expression, and by Cellular Thermal shift assay (CETSA) to check potential DHS or RSV-SIRT1 interaction. Transfection experiments have been performed with two SIRT1 mutants, based on the potential binding pockets identified by Molecular Docking analysis.

Results and conclusion

We unexpectedly found that DHS, but not RSV, exerted a time-dependent inhibitory effect on both SIRT1 protein levels and activity, the latter measured as p53 acetylation. At the mRNA level no significant changes were observed, whereas a proteasome-dependent mechanism was highlighted for the reduction of SIRT1 levels by DHS in experiments performed with the proteasome inhibitor MG132. Bioinformatics analysis suggested a higher affinity of RSV in binding all SIRT1 complexes compared to DHS, except comparable results for complex SIRT1-p53. Nevertheless, both CETSA and SIRT1 mutants transfected in cells did not confirm this interaction. In conclusion, DHS reduces SIRT1 protein level, thereby inhibiting its activity through a proteasome-mediated mechanism.

背景和目的白藜芦醇(RSV)是一种以芪类化合物为基础的化合物,具有广泛的生物学特性。其类似物 4,4′-二羟基-反式-白藜芦醇(DHS)在体外和体内显示出更高的生物利用度和抗增殖活性。关于白藜芦醇如何发挥作用的假说之一是基于 SIRT1 的激活。实验过程在正常人肺成纤维细胞中使用 MTT 试验确定了 DHS 的孵育时间和浓度。收获未经处理、经 DHS 或 RSV 处理的细胞,并通过 Western 印迹法或 RT-PCR 进行分析,以评估 SIRT1 的水平/活性和表达情况,并通过细胞热转移试验(CETSA)检查 DHS 或 RSV 与 SIRT1 的潜在相互作用。根据分子对接分析确定的潜在结合口袋,用两个 SIRT1 突变体进行了转染实验。结果和结论我们意外地发现,DHS 而不是 RSV 对 SIRT1 蛋白水平和活性(后者以 p53 乙酰化衡量)都有时间依赖性抑制作用。在 mRNA 水平上没有观察到明显的变化,而在使用蛋白酶体抑制剂 MG132 进行的实验中,DHS 对 SIRT1 水平的降低凸显了蛋白酶体依赖性机制。生物信息学分析表明,与 DHS 相比,RSV 与所有 SIRT1 复合物的结合亲和力都更高,但与 SIRT1-p53 复合物的结合结果不相上下。然而,转染细胞的 CETSA 和 SIRT1 突变体并未证实这种相互作用。总之,DHS 可降低 SIRT1 蛋白水平,从而通过蛋白酶体介导的机制抑制其活性。
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引用次数: 0
Jintiange capsule ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats by regulating the activity and differentiation of BMSCs 金天戈胶囊通过调节BMSCs的活性和分化改善糖皮质激素诱发的大鼠股骨头坏死
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-07 DOI: 10.1016/j.jtcme.2024.03.013

Background and aim

A surplus of glucocorticoids (GC) is a main cause of non-traumatic osteonecrosis of the femoral head (ONFH), and Jintiange (JTG), as one of the traditional Chinese medicines (TCM), also plays an instrumental role in the alleviation of bone loss simultaneously. Therefore, JTG was thought to be able to reverse GC-induced ONFH (GC-ONFH) to a certain extent.

Experimental procedure

In vivo, the effect of JTG on trabeculae in the subchondral bone of the femoral head was investigated using micro-computed tomography (micro-CT), TdT-mediated dUTP nick end labeling (TUNEL) and histological staining; in vitro, proliferation, viability, apoptosis, and senescence of purified bone mesenchymal stem cells (BMSCs) were examined to demonstrate the direct impact of JTG on these cells. Meanwhile after using a series of interventions, the function of JTG on BMSC differentiation could be assessed by measuring of osteogenic and adipogenic markers at levels of protein and mRNA.

Results

Our final results demonstrated that with the involvement of Wnt/β-catenin pathway, JTG was able to significantly promote osteogenesis, restrain adipogenesis, delay senescence in BMSCs, reduce osteoclast number, weaken apoptosis, and enhance proliferation of osteocytes, all of which could mitigate the progression of subchondral osteonecrosis.

Conclusion

According to the results of experiments in vitro and vivo, JTG was deemed to relieve the early GC-ONFH using the prevention of destruction of subchondral bone, which was contributed to regulating the differentiation of BMSCs and the number of osteoclasts.

背景和目的 糖皮质激素(GC)过剩是导致非创伤性股骨头坏死(ONFH)的主要原因,而金天歌作为传统中药之一,在缓解骨质流失方面也同时发挥着重要作用。因此,人们认为金天格能在一定程度上逆转 GC 诱导的 ONFH(GC-ONFH)。实验过程在体内,使用显微计算机断层扫描(micro-CT)、TdT介导的dUTP缺口末端标记(TUNEL)和组织学染色法研究了JTG对股骨头软骨下骨小梁的影响;在体外,研究了纯化的骨间充质干细胞(BMSCs)的增殖、活力、凋亡和衰老,以证明JTG对这些细胞的直接影响。同时,在使用一系列干预措施后,JTG 对骨间充质干细胞分化的作用可通过测量蛋白质和 mRNA 水平的成骨和成脂标志物来评估。结果我们的最终结果表明,在Wnt/β-catenin通路的参与下,JTG能显著促进BMSCs的成骨、抑制脂肪生成、延缓衰老、减少破骨细胞数量、减弱细胞凋亡、促进成骨细胞增殖,这些作用都能缓解软骨下骨坏死的进展。结论根据体外和体内的实验结果,JTG可通过防止软骨下骨的破坏来缓解早期GC-ONFH,这有助于调节BMSCs的分化和破骨细胞的数量。
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引用次数: 0
Phase 1 clinical trial evaluating safety, bioavailability, and gut microbiome with a combination of curcumin and ursolic acid in lipid enhanced capsules 评估姜黄素和熊果酸脂质强化胶囊组合的安全性、生物利用率和肠道微生物组的 1 期临床试验
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-07 DOI: 10.1016/j.jtcme.2024.03.002

As screening strategies employ better biomarkers and genetics to identify individuals at an increased risk of prostate cancer, there are currently no chemotherapeutic prevention strategies. With any chemoprevention strategy, the population will be younger and healthier; therefore, they will be less tolerant of side effects. This study translated findings from screening a natural product library and pre-clinical evaluation of curcumin (CURC) in combination with ursolic acid (UA) in prostate cancer models. After manufacturing capsules for each compound, 18 subjects were enrolled. The study used a 3 × 3 phase 1 clinical trial to evaluate CURC (1200 mg/day) and UA (300 mg/day) alone and in combination over a 2-week period with endpoints of safety, bioavailability, and microbiome alterations. After enrolling six subjects in each arm, we found no grade 3 or 4 events and only minor changes in the safety laboratory values. In the pooled analysis of groups, we noted a statistically significant difference between median serum levels of UA when administered alone vs administered in the combination (2.7 ng/mL vs 43.8 ng/mL, p = 0.03). Individuals receiving the combination also had a favorable impact on gut microbiome status and a reduction in “microbiome score” predictive of prostate cancer risk.

由于筛查策略采用了更好的生物标志物和遗传学方法来确定前列腺癌的高危人群,目前还没有化疗预防策略。任何化学预防策略的适用人群都将更年轻、更健康;因此,他们对副作用的耐受性将更低。本研究将筛选天然产品库和姜黄素(CURC)与熊果酸(UA)联合用于前列腺癌模型的临床前评估结果进行了转化。在为每种化合物生产胶囊后,共招募了 18 名受试者。该研究采用 3 × 3 的 1 期临床试验,对 CURC(1200 毫克/天)和 UA(300 毫克/天)在 2 周时间内单独或联合使用进行评估,终点是安全性、生物利用度和微生物组改变。在每组招募 6 名受试者后,我们未发现 3 级或 4 级事件,安全性实验室值也仅有轻微变化。在各组的汇总分析中,我们注意到单独用药与联合用药的 UA 血清中位数水平之间存在显著的统计学差异(2.7 纳克/毫升 vs 43.8 纳克/毫升,p = 0.03)。接受联合用药的个体还对肠道微生物组状态产生了有利影响,并降低了预测前列腺癌风险的 "微生物组评分"。
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引用次数: 0
Chemical profiling and mechanisms of Agarikon pill in a rat model of cigarette smoke-induced chronic obstructive pulmonary disease 阿加瑞康丸在香烟烟雾诱发慢性阻塞性肺病大鼠模型中的化学分析和作用机制
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-06 DOI: 10.1016/j.jtcme.2024.03.006

Background and aim

Agarikon pill (AGKP), a traditional Chinese herbal formula, and has been used for chronic obstructive pulmonary disease (COPD) treatment clinically. However, the active components and exact pharmacological mechanisms are still unclear. We aimed to investigate the therapeutic effects and mechanisms of AGKP on COPD and identify the chemical constituents and active compounds.

Experimental procedure

The chemical components of AGKP were identified by ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Network pharmacology analysis was performed to uncover the potential mechanism of AGKP. The efficiencies and mechanisms of AGKP were further confirmed in COPD animal models.

Results and conclusion

Ninety compounds from AGKP, such as flavonoids, triterpenoids, saponins, anthracenes, derivatives, phenyl propionic acid, and other organic acids, were identified in our study. AGKP improved lung function and pathological changes in COPD model rats. Additionally, inflammatory cell infiltration and proinflammatory cytokine levels were markedly reduced in COPD rats administered AGKP. Network pharmacology analysis showed that the inflammatory response is the crucial mechanism by which AGKP exerts therapeutic effects on COPD rats. WB and PCR data indicated that AGKP attenuated the inflammatory response in COPD model rats. AGKP reduces the pulmonary inflammatory response through the PI3K/AKT and MAPK TLR/NF-κB signaling pathways and exerts therapeutic effects via inhibition of inflammation and mucus hypersecretion on COPD model rats.

背景和目的阿胶浆(AGKP)是一种传统的中药配方,临床上一直用于慢性阻塞性肺病(COPD)的治疗。然而,其活性成分和确切的药理机制仍不清楚。实验过程采用超高效液相色谱-四极杆/比特阱高分辨质谱(UHPLC-Q-Orbitrap-HRMS)鉴定 AGKP 的化学成分。为揭示 AGKP 的潜在机制,研究人员进行了网络药理学分析。结果与结论我们的研究从 AGKP 中鉴定出 90 种化合物,如黄酮类、三萜类、皂苷类、蒽类、衍生物、苯丙酸和其他有机酸。AGKP 可改善慢性阻塞性肺疾病模型大鼠的肺功能和病理变化。此外,给慢性阻塞性肺病大鼠服用 AGKP 后,炎症细胞浸润和促炎细胞因子水平明显降低。网络药理学分析表明,炎症反应是 AGKP 对慢性阻塞性肺病大鼠产生治疗效果的关键机制。WB 和 PCR 数据表明,AGKP 可减轻 COPD 模型大鼠的炎症反应。AGKP通过PI3K/AKT和MAPK TLR/NF-κB信号通路降低肺部炎症反应,并通过抑制炎症和粘液高分泌对慢性阻塞性肺病模型大鼠产生治疗效果。
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引用次数: 0
Exploring hepatic fibrosis screening via deep learning analysis of tongue images 通过舌头图像的深度学习分析探索肝纤维化筛查
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-06 DOI: 10.1016/j.jtcme.2024.03.010

Background

Tongue inspection, an essential diagnostic method in Traditional Chinese Medicine (TCM), has the potential for early-stage disease screening. This study aimed to evaluate the effectiveness of deep learning-based analysis of tongue images for hepatic fibrosis screening.

Methods

A total of 1083 tongue images were collected from 741 patients and divided into training, validation, and test sets. DenseNet-201, a convolutional neural network, was employed to train the AI model using these tongue images. The predictive performance of AI was assessed and compared with that of FIB-4, using real-time two-dimensional shear wave elastography as the reference standard.

Results

The proposed AI model achieved an accuracy of 0.845 (95% CI: 0.79–0.90) and 0.814 (95% CI: 0.76–0.87) in the validation and test sets, respectively, with negative predictive values (NPVs) exceeding 90% in both sets. The AI model outperformed FIB-4 in all aspects, and when combined with FIB-4, the NPV reached 94.4%.

Conclusion

Tongue inspection, with the assistance of AI, could serve as a first-line screening method for hepatic fibrosis.

背景舌象检查是中医(TCM)的一种重要诊断方法,具有早期疾病筛查的潜力。本研究旨在评估基于深度学习的舌象分析在肝纤维化筛查中的有效性。方法从 741 名患者身上共收集了 1083 张舌象,并将其分为训练集、验证集和测试集。采用卷积神经网络 DenseNet-201 利用这些舌头图像训练人工智能模型。结果所提出的人工智能模型在验证集和测试集中的准确率分别达到了 0.845(95% CI:0.79-0.90)和 0.814(95% CI:0.76-0.87),负预测值(NPV)均超过了 90%。人工智能模型在所有方面都优于 FIB-4,当与 FIB-4 结合使用时,NPV 达到 94.4%。
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引用次数: 0
Chinese herbal medicine may reduce major adverse cardiovascular events in patients with dialysis hypotension: A taiwan nationwide cohort study 中药可减少透析低血压患者的主要心血管不良事件:一项台湾全国性队列研究
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-06 DOI: 10.1016/j.jtcme.2024.03.009

Background

The association between Chinese herbal medicine (CHM) and the risk of developing major adverse cardiovascular events (MACEs) in patients with dialysis hypotension is unclear and has not yet been investigated. This study aimed to determine whether CMH intervention could reduce the risk of MACEs in patients with dialysis hypotension.

Methods

The study data from the Taiwan National Health Insurance Research Database were analyzed to clarify this association. For this study, a case-control design with a cohort of patients who received hemodialysis (HD) from 2008 to 2018, 20 295 HD patients who had received blood pressure (BP) raising drugs were identified. After 1:1 frequency-matching, 730 patients were identified as CHM users and CHM non-users. Vascular access revision/reconstruction and MACEs were observed as the main outcomes during the follow-up period.

Results

The occurrence of vascular access revision/reconstruction in HD patients receiving BP raising drugs was associated with a 0.34-fold lower risk in CHM users than in CHM non-users [adjusted hazard ratio (aHR) = 0.34, 95% confidence interval (CI) = 0.26, 0.45]. The occurrences of MACEs in HD patients receiving BP raising drugs was associated with a 0.41-fold lower risk in CHM users than in CHM non-users (aHR = 0.41, 95% CI = 0.33, 0.51). A markedly predominant effect was observed in those receiving CHM for more than 180 days (aHR = 0.32; 95% CI = 0.22, 0.45).

Conclusion

The findings revealed lower vascular access dysfunction and MACEs risk correlated with the use of CHM treatment among HD patients who received BP raising drugs.

背景中药与透析低血压患者发生主要不良心血管事件(MACEs)风险之间的关系尚不明确,也尚未进行过研究。本研究旨在确定中药干预是否能降低透析低血压患者的 MACE 风险。本研究采用病例对照设计,以2008年至2018年接受血液透析(HD)的患者为队列,共确定了20 295名接受过升压药物治疗的HD患者。经过1:1频率匹配后,730名患者被确定为CHM使用者和非CHM使用者。结果在接受升压药物治疗的 HD 患者中,使用 CHM 的患者发生血管通路修正/重建的风险比未使用 CHM 的患者低 0.34 倍[调整后危险比 (aHR) = 0.34,95% 置信区间 (CI) = 0.26,0.45]。在接受升压药物治疗的 HD 患者中,使用 CHM 的患者发生 MACE 的风险比未使用 CHM 的患者低 0.41 倍(aHR = 0.41,95% CI = 0.33,0.51)。结论研究结果表明,在接受降压药治疗的 HD 患者中,血管通路功能障碍和 MACEs 风险的降低与使用 CHM 治疗相关。
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引用次数: 0
Zhilong Huoxue Tongyu capsule protects against atherosclerosis by suppressing End MT via modulating Hippo/YAP signaling pathway 芝龙藿香通脉胶囊通过调节 Hippo/YAP 信号通路抑制 End MT 防止动脉粥样硬化
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.jtcme.2024.03.015
Yanan Zhou, Hong Wang, Tao Bi, P. Liang, Xinyue Liu, Hongping Shen, Qin Sun, Gang Luo, Ping Liu, Sijin Yang, Wei-Ming Ren
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引用次数: 0
Antcin-H, a natural triterpene derived from Antrodia cinnamomea, ameliorates dextran sulfate sodium-induced colitis in mice by inhibiting the NLRP3 inflammasome Antcin-H 是一种从桂枝中提取的天然三萜类化合物,可通过抑制 NLRP3 炎性体改善右旋糖酐硫酸钠诱导的小鼠结肠炎
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.jtcme.2024.03.016
Wei-Ting Wong, Lan-hui Li, Hsiao-Wen Chiu, M. Menon, Hsien-Ta Hsu, Wen-Yu Lin, Chun-Hsien Wu, Chen-Lung Ho, Kuo-Feng Hua
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引用次数: 0
期刊
Journal of Traditional and Complementary Medicine
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