Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03929-4
Background Influence on stem cells' angiogenesis and osteogenesis of NAD(P)H Quinone Dehydrogenase 1(NQO1) has been established, but its impact on dental pulp stem cells (DPSCs) is unexplored. An important strategy for the treatment of arteriosclerosis is to inhibit calcium deposition and to promote vascular repair and angiogenesis. This study investigated the function and mechanism of NQO1 on angiogenesis and osteogenesis of DPSCs, so as to provide a new ideal for the treatment of arteriosclerosis. Methods Co-culture of human DPSCs and human umbilical vein endothelial cells (HUVECs) was used to detect the angiogenesis ability. Alkaline phosphatase (ALP) activity, alizarin red staining (ARS), and transplantation of HA/tri-calcium phosphate with DPSCs were used to detect osteogenesis. Results NQO1 suppressed in vitro tubule formation, migration, chemotaxis, and in vivo angiogenesis, as evidenced by reduced CD31 expression. It also enhanced ALP activity, ARS, DSPP expression and osteogenesis and boosted mitochondrial function in DPSCs. CoQ10, an electron transport chain activator, counteracted the effects of NQO1 knockdown on these processes. Additionally, NQO1 downregulated MAPK signaling, which was reversed by CoQ10 supplementation in DPSCs-NQO1sh. Conclusions NQO1 inhibited angiogenesis and promoted the osteogenesis of DPSCs by suppressing MAPK signaling pathways and enhancing mitochondrial respiration.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023285
Cisplatin (CDDP) is a widely used chemotherapeutic agent that has remarkable antineoplastic effects. However, CDDP can cause severe acute kidney injury (AKI), which limits its clinical application. Agrimol B is the main active ingredient found in Agrimonia pilosa Ledeb and has a variety of pharmacological activities. The effect of agrimol B on CDDP-induced renal toxicity has not been determined. To investigate whether agrimol B has a protective effect against CDDP-induced AKI, we first identify Sirtuin 1 (Sirt1) as a critical target protein of agrimol B in regulating AKI through network pharmacology analysis. Subsequently, the AKI mouse model is induced by administering a single dose of CDDP via intraperitoneal injection. By detecting the serum urea nitrogen and creatinine levels, as well as the histopathological changes, we confirm that agrimol B effectively reduces CDDP-induced AKI. In addition, treatment with agrimol B counteracts the increase in renal malondialdehyde level and the decrease in superoxide dismutase (SOD), catalase and glutathione levels induced by CDDP. Moreover, western blot results reveal that agrimol B upregulates the expressions of Sirt1, SOD2, nuclear factor erythroid2-related factor 2, and downstream molecules, including heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1. However, administration of the Sirt1 inhibitor EX527 abolishes the effects of agrimol B. Finally, we establish a tumor-bearing mouse model and find that agrimol B has a synergistic antitumor effect with CDDP. Overall, agrimol B attenuates CDDP-induced AKI by activating the Sirt1/Nrf2 signaling pathway to counteract oxidative stress, suggesting that this compound is a potential therapeutic agent for the treatment of CDDP-induced AKI.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261634
The toxicity of traditional Chinese medicines (TCMs) constitutes a core component of pharmacological theory, alongside the four natures and five flavors, ascending-descending-floating-sinking, and channel tropism, collectively guiding clinical TCM practice. Highly toxic medicinal materials present formidable challenges: their complex compositions impede full elucidation of toxic constituents and mechanisms, while diverse clinical regimens and significant individual variability further complicate research. This review systematically examines highly toxic medicinal materials listed in the 2025 edition of the Chinese Pharmacopoeia. Integrating herbal textual research with modern pharmacological investigations, it analyzes common toxic components and pathways, the bidirectional toxicity-efficacy relationship, and strategies for reducing toxicity while preserving efficacy. The application of modern analytical detection techniques in quality control is reviewed, and other potentially toxic substances and risk management strategies are discussed. The 2025 Pharmacopoeia classifies highly toxic materials primarily as plant-derived, imposing strict regulations on dosage forms, pregnancy contraindications, compatibility contraindications, usage, and special population restrictions. Historical toxicity grading has evolved; for instance, Chuanwu (Aconiti Lateralis Radix Praeparata) was recorded as 'toxic' in Wupu Bencao but as 'highly toxic' in Mingyi Bielu and Yaoxing Lun. Advanced analytical tools such as HPLC-MS have enabled fingerprinting and identification of over 50 highly toxic compounds, including aconitine-type alkaloids and brucine. Mechanistic studies based on apoptotic signaling pathways and metabolomics have revealed complex 'biphasic toxicity effects.' Traditional processing detoxification and compatibility antagonism have been scientifically validated and optimized. However, challenges persist, particularly the incomplete 'component-toxicity' association, which restricts clinical dosage ranges and elevates potential risks, constraining further clinical application. This review aims to provide a scientific reference for deepening quality standard research and promoting safe, rational clinical use of highly toxic medicinal materials.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21228
BACKGROUND: Vascular injury-related diseases have garnered significant attention in the medical field, and the browning of perivascular adipose tissue is closely linked to these diseases. However, the regulatory mechanisms of specific genes involved in this process remain unclear. OBJECTIVE: To investigate the potential mechanism by which iroquois homeobox 3 regulates the browning of perivascular adipose tissue in vascular injury. METHODS: The perivascular adipose tissue-related single-cell sequencing data matrix GSE275779 was analyzed to investigate the expression levels and functions of iroquois homeobox 3 in various cell subpopulations. In conjunction with adipocyte-related microarray and sequencing data GSE44059, GSE7032, GSE185518, and GSE168387, differentially expressed genes were identified, and the expression level of iroquois homeobox 3 during the differentiation of browning adipocytes was validated. The downstream target genes of iroquois homeobox 3 were screened using the msigdb database and the ChIP-seq database GTRD. By disrupting iroquois homeobox 3 and overexpressing retinol saturase in adipocyte precursor cells, the mRNA and protein expression levels of browning-related genes were detected by qPCR and western blot. RESULTS AND CONCLUSION: Bioinformatics analysis showed that adipocyte characteristic factors such as PR domain containing 16, cell death-inducing DFFA-like effector A, and uncoupling protein 1 were significantly downregulated in perivascular adipose tissue of diabetic patients, and these genes are involved in adipose browning. Combined with high-throughput sequencing data analysis, it was found that iroquois homeobox 3 is highly expressed in brown adipose tissue and participates in brown adipocyte differentiation. Further screening identified retinol saturase as a downstream target gene of iroquois homeobox 3, and its level was differentially expressed during brown adipocyte differentiation. In mature brown adipocytes, knockdown of iroquois homeobox 3 led to decreased expression of retinol saturase and browning-related markers (uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, PR domain containing 16). In the retinol saturase rescue experiment, overexpression of retinol saturase significantly upregulated the protein levels of browning-related markers but did not affect the expression of iroquois homeobox 3. This study preliminarily reveals the potential mechanism by which iroquois homeobox 3 regulates perivascular adipose tissue browning during vascular injury.
Chinese Journal of New Drugs•2025•DOI: pub_80__articleID_236
Background: High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality for uterine fibroids. However, its efficacy and safety compared with conventional surgery remain debated. Methods: In this multicenter, randomized, controlled trial, we randomly assigned 200 women with symptomatic uterine fibroids to undergo HIFU ablation (n=100) or myomectomy (n=100). The primary endpoint was the reduction in fibroid volume at 6 months. Secondary endpoints included symptom severity score, quality of life, and adverse events. Results: At 6 months, the mean reduction in fibroid volume was 45.2% in the HIFU group versus 58.7% in the surgery group (P<0.001). Symptom severity scores improved significantly in both groups, with no significant difference between groups (P=0.32). Quality of life scores were comparable. Adverse events were fewer in the HIFU group (12% vs. 28%, P=0.004). Conclusion: HIFU is a safe and effective alternative to surgery for symptomatic uterine fibroids, offering comparable symptomatic relief with fewer adverse events, despite a smaller reduction in fibroid volume.