Study on the anti-atherosclerosis mechanisms of Tanyu Tongzhi formula based on network pharmacology, Mendelian randomization, and experimental verification

Article

作者: Zhou, Xinbin ; Xu, Xiaoming ; Dai, Jin ; Qiu, Yuangang ; Chen, Shenjie ; Mao, Wei

CONTEXTTanyu Tongzhi Formula (TTF) exhibits potential against atherosclerosis; however, its mechanisms remain unclear.OBJECTIVEThis study explores the pharmacological mechanisms of TTF in treating atherosclerosis.MATERIALS AND METHODSNetwork pharmacology, molecular docking, mendelian randomization (MR), and liquid chromatography-mass spectrometry (LC-MS) analyses were utilized to reveal potential targets and compounds of TTF against atherosclerosis. After exploring the appropriate concentration of TTF to treat HCAECs using Cell Counting Kit-8 (CCK-8), the HCAECs were divided into three groups: control, oxidized low-density lipoprotein (ox-LDL, 50 μg/mL), and ox-LDL (50 μg/mL) + TTF (1 mg/mL). After 24-h incubation, the efficacy of TTF was verified by CCK-8, Oil red O staining, and ELISA. The expression of key targets was detected by real-time polymerase chain reaction (qPCR) and western blotting.RESULTSA total of 137 active compounds and 127 potential TTF targets against atherosclerosis were identified. MR identified ALB, TNF, PPARα, and PPARγ as key targets. Molecular docking indicated that baicalin, naringenin, and curcumin exhibited suitable binding activities to these targets, further confirming by LC-MS analysis. The IC₅₀ of TTF in HCAECs was 18.25 mg/mL. TTF treatment significantly improved atherosclerosis by enhancing cell viability, reducing lipid accumulation, and inhibiting inflammation factors (IL6, IL1B and TNF-α) in ox-LDL-treated HCAECs. Moreover, qPCR or western blotting indicated that TTF could up-regulate PPARα and PPARγ while down-regulate TNF expression.DISCUSSION AND CONCLUSIONSOur results revealed active compounds, key pathways, and core targets of TTF against atherosclerosis, providing experimental support for its application in treating of atherosclerosis.

2024-08-01·Chinese Clinical Oncology

AB011. A propensity-score matched prospective study on the impact of tumour treating fields (TTF) on overall survival and quality of life in newly diagnosed WHO grade 4 astrocytoma patients

Article

作者: Wong, Desiree K. K. ; Chan, Danny T. M. ; Chow, Joyce S W ; Li, Lai-Fung ; Chan, Tony K. T. ; Lam, Sandy W. ; Woo, Peter Y. M. ; Chan, Tony K T ; Lam, Sandy W ; Lee, Michael W. Y. ; Cheung, Fung-Ching ; Chow, Joyce S. W. ; Wong, Desiree K K ; Ko, Natalie M. W. ; Ko, Natalie M W ; Chan, Danny T M ; Woo, Peter Y M ; Wong, Sui-To ; Lee, Michael W Y

BACKGROUNDWorld Health Organization (WHO) grade 4 astrocytoma is a high-grade brain tumour in adults. Tumour treating fields (TTF) has been shown to improve overall survival (OS). Few studies have explored quality-of-life (QoL) in these patients. This study aims to assess the QoL of TTF patients and OS.METHODSThis was a prospective multicenter study of adult patients diagnosed with WHO grade 4 astrocytoma from 2018 to 2023 receiving TTF for >1 month after completing standard therapy. A propensity-score matched comparison with a 1:2 ratio with historical control was performed for OS analysis. The patients completed European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30/BN20 questionnaires before TTF and at 3-month interval. Primary outcomes included OS, and secondary outcomes included QoL and TTF-associated adverse effects at 3 months.RESULTSA total of 141 patients were reviewed, with TTF patients (n=47, 33%) and propensity-score matched controls (n=94). The mean duration of TTF use was 10±8 months. The mean age of the TTF group was 54±13 years, and for the control group 52±13 years. Sixty percent (n=28) were male, similar to the control group with 71% (n=67) (P=0.16). Seventy-two percent of TTF patients had preoperative Karnofsky Performance Scale (KPS) score ≥80, while controls had 70% (P=0.79). Five (11%) TTF patients and 8 (9%) controls were IDH1 mutant (P=0.70). Twenty (43%) TTF patients and 42 (45%) controls were O6-methylguanine-DNA methyltransferase promoter (pMGMT) methylated (P=0.81). Twenty-one (45%) of TTF patients and 55 (59%) of controls had gross total resection (P=0.72). After adjusting for independent predictors for OS, the median OS of the TTF group was 22.4 months [interquartile range (IQR): 18.6-26.5 months], significantly longer than the control group (17.2 months; IQR: 12.1-22.3 months) (log-rank test: P=0.01). Forty-seven TTF patients and 40 control patients completed EORTC questionnaires. There was no difference for EORTC functional and symptom scores between the TTF and control group [P=0.45, analysis of variance (ANOVA)] at 3 months. Thirty-two (67%) of TTF patients reported associated RTOG grade I scalp dermatitis.CONCLUSIONSTTF for WHO grade 4 astrocytoma patients is an independent predictor for OS. QoL between the groups was similar, and overall QoL over time for TTF patients was not affected. TTF is a novel and effective outpatient treatment with minimal adverse effects.

2022-06-01·Journal of Neuro-Oncology2区 · 医学

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults

2区 · 医学

Review

作者: Ormond, D Ryan ; Wen, Patrick ; Ziu, Mateo ; Olson, Jeffrey J ; Germano, Isabelle M

TARGET POPULATIONThese recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM). QUESTION (Q1): In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?RECOMMENDATIONLevel III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5 months of TMZ-treatment free interval.LEVEL IIICombination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy. There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits. QUESTION (Q2): In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?RECOMMENDATIONLevel III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen. QUESTION (Q3): In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?RECOMMENDATIONLevel III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.LEVEL IIIOther cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy. QUESTION (Q4): In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?RECOMMENDATIONLevel III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM. QUESTION (Q5): In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?RECOMMENDATIONLevel III: Oncolytic virotherapy is not suggested in patients with pGBM.

100 项与 tTF-RGD (University of Muenster) 相关的药物交易

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