Isogarcinol inhibits nasopharyngeal carcinoma growth through mitochondria-mediated autophagic cell death.

BACKGROUND AND AIMS: Isogarcinol, a natural compound extracted from the fruits of Garcinia oblongifolia, has potential chemopreventive activity. This study aimed to elucidate the anti-tumor effects and mechanism of action of isogarcinol on nasopharyngeal carcinoma (NPC). METHODS: Isogarcinol was isolated from Garcinia oblongifolia by using chromatographic separation. The anti-tumor effects of isogarcinol in NPC cells were tested by MTT assay, flow cytometry, wound healing assay, western blotting, transwell assay, colony formation assay, immunofluorescence, and transmission electron microscopy (TEM). The anti-tumor efficacy in vivo was evaluated in NPC cells xenograft models. RESULTS: Functional studies revealed that isogarcinol inhibited the proliferation, colony formation, migration and invasion abilities of NPC cells in vitro. Isogarcinol caused mitochondrial damage to overproduce reactive oxygen species through reducing the mitochondrial membrane potential and ΔΨm. Isogarcinol also substantially inhibited NPC cells growth in a xenograft tumor model without any obvious toxicity when compared with paclitaxel (PTX). Mechanistic studies have illustrated that isogarcinol increased the Bax/Bcl-2 ratio, cleaved caspase-3, and cytoplasmic cytochrome C levels to induce mitochondrial apoptosis. The ROS overproduction by isogarcinol could suppress EMT pathway via decreasing the levels of p-Akt and Snail. Furthermore, isogarcinol promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, but increased p62 level to block autophagic flux, resulting in the accumulation of damaged mitochondria to promote autophagic cell death in NPC cells. CONCLUSION: This study provides a new theoretical foundation for the anti-tumor application of Garcinia oblongifolia and confirms that isogarcinol could be developed as a candidate drug for NPC treatment with low toxicity.

Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.

Osteogenic Induction and Anti-inflammatory Effects of Calcium-Chlorogenic Acid Nanoparticles Remodel the Osteoimmunology Microenvironment for Accelerating Bone Repair.

Successful bone regeneration requires the close cooperation between bone marrow mesenchymal stem cells (BMSCs) and macrophages, but the low osteogenic differentiation efficiency of stem cells and the excessive inflammatory response of immune cells hinder the development of the bone repair. It is necessary to develop a strategy that simultaneously regulates the osteogenic differentiation of BMSCs and the anti-inflammatory polarization of macrophages for accelerating the bone regeneration. Herein, calcium-chlorogenic acid nanoparticles (Ca-CGA NPs) were synthesized by combining the small molecular of chlorogenic acid (CGA) with Ca2+. Ca-CGA NPs internalized by cells could be dissolved to release free CGA and Ca2+ under low pH conditions in lysosomes. In vitro results demonstrated that Ca-CGA NPs could not only enhance the osteogenic differentiation of BMSCs, but also promote the phenotype transformation of macrophages from M1 to M2. Furthermore, in vivo experiments confirmed that Ca-CGA NPs treatment facilitated the recovery of rat skull defect model through both the osteoinduction and immunomodulation. This study develops a new Ca-CGA NPs-based strategy to induce the differentiation of BMSCs into osteoblasts and the polarization of macrophages into M2 phenotype, which is promising for accelerating bone repair. This article is protected by copyright. All rights reserved.

Wireless Electrical Signals Induce Functional Neuronal Differentiation of BMSCs on 3D Graphene Framework Driven by Magnetic Field.

Bone marrow mesenchymal stem cells (BMSCs) are suggested as candidates for neurodegeneration therapy by autologous stem cells to overcome the lack of neural stem cells in adults. However, the differentiation of BMSCs into functional neurons is a major challenge for neurotherapy. Herein, a methodology has been proposed to induce functional neuronal differentiation of BMSCs on a conductive three-dimensional graphene framework (GFs) combined with a rotating magnetic field. A wireless electrical signal of about 10 µA can be generated on the surface of GFs by cutting the magnetic field lines based on the well-known electromagnetic induction effect, which has been proven to be suitable for inducing neuronal differentiation of BMSCs. The enhanced expressions of the specific genes/proteins and apparent Ca2+ intracellular flow indicate that BMSCs cultured on GFs with 15 min/day rotating magnetic field stimulation for 15 days can differentiate functional neurons without any neural inducing factor. The animal experiments confirm the neural differentiation of BMSCs on GFs after transplantation in vivo, accompanied by stimulation of an external rotating magnetic field. This study overcomes the lack of autologous neural stem cells for adult neurodegeneration patients and provides a facile and safe strategy to induce the neural differentiation of BMSCs, which has potential for clinical applications of neural tissue engineering.

Biomineralization Process of CaCO3 Precipitation Induced by Bacillus mucilaginous and Its Potential Application in Microbial Self-healing Concrete.

Microbial induced calcium carbonate precipitation (MICP) is widely common in nature, which belongs to biomineralization and has been explored carefully in recent decades. The paper studied the effect of temperature, initial pH value and Ca2+ concentration on bacterial growth and carbonic anhydrase activity, and then revealed the biomineralization process through the changes of Ca2+ concentration and calcification rate in alkali environment. Meanwhile, microbial healing agent containing spores and calcium nitrate was prepared and used for the early age concrete cracks repair. The self-healing efficiency was assessed by crack closure rate and water permeability repair rate. The experimental results showed that when the optimal temperature was 30 °C, the pH was 8.0-11.0, and the optimal Ca2+ concentration was 0-90 mM, the bacteria could grow better and the carbonic anhydrase activity was higher. Compared with reference, the crack closure rate with the crack width up to 0.339 mm could reach 95.62% and the water permeability repair rate was 87.54% after 28 d healing time of dry-wet cycles. XRD analysis showed that the precipitates at the crack mouth were calcite CaCO3. Meanwhile, the self-healing mechanism of mortar cracks was discussed in detail. In particular, there is no other pollution in the whole mineralization process, and the self-healing system is environmentally friendly, which provides a novel idea and method for the application of microbial self-healing concrete.

Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer.

Introduction: Gastric cancer (GC) is the fifth most common tumor, contributing to the third-highest number of cancer-related deaths. Hypoxia is a major feature of the tumor microenvironment. This study aimed to explore the influence of hypoxia in GC and establish a hypoxia-related prognostic panel. Methods: The GC scRNA-seq data and bulk RNA-seq data were downloaded from the GEO and TCGA databases, respectively. AddModuleScore() and AUCell() were used to calculate module scores and fractions of enrichment for hypoxia-related gene expression in single cells. Least absolute shrinkage and selection operator cox (LASSO-COX) regression analysis was utilized to build a prognostic panel, and hub RNAs were validated by qPCR. The CIBERSORT algorithm was adopted to evaluate immune infiltration. The finding of immune infiltration was validated by a dual immunohistochemistry staining. The TIDE score, TIS score and ESTIMATE were used to evaluate the immunotherapy predictive efficacy. Results: Hypoxia-related scores were the highest in fibroblasts, and 166 differentially expressed genes were identified. Five hypoxia-related genes were incorporated into the hypoxia-related prognostic panel. 4 hypoxia-related genes (including POSTN, BMP4, MXRA5 and LBH) were significantly upregulated in clinical GC samples compared with the normal group, while APOD expression decreased in GC samples. Similar results were found between cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). A high hypoxia score was associated with advanced grade, TNM stage, N stage, and poorer prognosis. Decreased antitumor immune cells and increased cancer-promoting immune cells were found in patients with high hypoxia scores. Dual immunohistochemistry staining showed high expression of CD8 and ACTA2 in gastric cancer tissue. In addition, the high hypoxia score group possessed higher TIDE scores, indicating poor immunotherapy benefit. A high hypoxia score was also firmly related to sensitivity to chemotherapeutic drugs. Discussion: This hypoxia-related prognostic panel may be effective in predicting the clinical prognosis, immune infiltrations, immunotherapy, and chemotherapy in GC.

ShortcutLens: A Visual Analytics Approach for Exploring Shortcuts in Natural Language Understanding Dataset.

Benchmark datasets play an important role in evaluating Natural Language Understanding (NLU) models. However, shortcuts-unwanted biases in the benchmark datasets-can damage the effectiveness of benchmark datasets in revealing models' real capabilities. Since shortcuts vary in coverage, productivity, and semantic meaning, it is challenging for NLU experts to systematically understand and avoid them when creating benchmark datasets. In this paper, we develop a visual analytics system, ShortcutLens, to help NLU experts explore shortcuts in NLU benchmark datasets. The system allows users to conduct multi-level exploration of shortcuts. Specifically, Statistics View helps users grasp the statistics such as coverage and productivity of shortcuts in the benchmark dataset. Template View employs hierarchical and interpretable templates to summarize different types of shortcuts. Instance View allows users to check the corresponding instances covered by the shortcuts. We conduct case studies and expert interviews to evaluate the effectiveness and usability of the system. The results demonstrate that ShortcutLens supports users in gaining a better understanding of benchmark dataset issues through shortcuts, inspiring them to create challenging and pertinent benchmark datasets.

Retraction: MicroRNA-433 inhibits oral squamous cell carcinoma cells by targeting FAK.

[This retracts the article DOI: 10.18632/oncotarget.22151.].

Safrole oxide induced 5-HT neuron-like cell differentiation of bone marrow mesenchymal stem cells by elevating G9a.

In our previous study, we found that safrole oxide (SFO) could induce bone marrow mesenchymal stem cell differentiation into neuron-like cells. However, which kind of neuron cells was induced by SFO was unknown. Here, we found that SFO could induce BMSC differentiation into 5-hydroxytryptamine (5-HT) neuron-like cells. Microarray analysis of BMSCs treated with SFO for 6 h revealed a total of 35 genes changed more than twice. We selected G9a, a histone methyltransferase for further study. The upregulation of G9a was confirmed by RT-PCR and Western blot analysis. Small interfering RNA knockdown of G9a blocked SFO-induced BMSC differentiation. These results demonstrated that G9a was the pivotal factor in SFO-medicated 5-HT neuronal differentiation of BMSCs. Our findings provide a new clue for further investigating the gene control of BMSC differentiation into 5-HT neuron-like cells and provide a putative strategy for depression diseases therapies.

Gold Nanostrip Array-Mediated Wireless Electrical Stimulation for Accelerating Functional Neuronal Differentiation.

Neural stem cell (NSC)-based therapy holds great promise for the treatment of neurodegenerative diseases. Presently, however, it is hindered by poor functional neuronal differentiation. Electrical stimulation is considered one of the most effective ways to promote neuronal differentiation of NSCs. In addition to surgically implanted electrodes, traditional electrical stimulation includes wires connected to the external power supply, and an additional surgery is required to remove the electrodes or wires following stimulation, which may cause secondary injuries and infections. Herein, a novel method is reported for generation of wireless electrical signals on an Au nanostrip array by leveraging the effect of electromagnetic induction under a rotating magnetic field. The intensity of the generated electrical signals depends on the rotation speed and magnetic field strength. The Au nanostrip array-mediated electric stimulation promotes NSC differentiation into mature neurons within 5 days, at the mRNA, protein, and function levels. The rate of differentiation is faster by at least 5 days than that in cells without treatment. The Au nanostrip array-based wireless device also accelerates neuronal differentiation of NSCs in vivo. The novel method to accelerate the neuronal differentiation of NSCs has the advantages of wireless, timely, localized and precise controllability, and noninvasive power supplementation.

Stem Cell Membrane-Encapsulated Zeolitic Imidazolate Framework-8: A Targeted Nano-Platform for Osteogenic Differentiation.

Mesenchymal stem cells (MSCs) have been recognized as one of the most promising pharmaceutical multipotent cells, and a key step for their wide application is to safely and efficiently regulate their activities. Various methods have been proposed to regulate the directional differentiation of MSCs during tissue regeneration, such as nanoparticles and metal ions. Herein, nanoscale zeolitic imidazolate framework-8 (ZIF-8), a Zn-based metal-organic framework, is modified to direct MSCs toward an osteoblast lineage. Specifically, ZIF-8 nanoparticles are encapsulated using stem cell membranes (SCMs) to mimic natural molecules and improve the biocompatibility and targeted ability toward MSCs. SCM/ZIF-8 nanoparticles adjust the sustained release of Zn2+ , and promote their specific internalization toward MSCs. The internalized SCM/ZIF-8 nanoparticles show excellent biocompatibility, and increase MSCs' osteogenic potentials. Moreover, RNA-sequencing results elucidate that the activated cyclic adenosine 3,5-monophosphate (cAMP)-PKA-CREB signaling pathway can be dominant in accelerating osteogenic differentiation. In vivo, SCM/ZIF-8 nanoparticles greatly promote the formation of new bone tissue in the femoral bone defect detected by 3D micro-CT, hematoxylin and eosin staining, and Masson staining after 4 weeks. Overall, the SCM-derived ZIF-8 nanostructures achieve the superior targeting ability, biocompatibility, and enhanced osteogenesis, providing a constructive design for tissue repair.

Dihydrohomoplantagin and Homoplantaginin, Major Flavonoid Glycosides from Salvia plebeia R. Br. Inhibit oxLDL-Induced Endothelial Cell Injury and Restrict Atherosclerosis via Activating Nrf2 Anti-Oxidation Signal Pathway.

Oxidized low-density lipoprotein (oxLDL)-induced endothelium injury promotes the development of atherosclerosis. It has been reported that homoplantaginin, a flavonoid glycoside from the traditional Chinese medicine Salvia plebeia R. Br., protected vascular endothelial cells by inhibiting inflammation. However, it is undetermined whether homoplantaginin affects atherosclerosis. In this study, we evaluated the effect of homoplantaginin and its derivative dihydrohomoplantagin on oxLDL-induced endothelial cell injury and atherosclerosis in apoE-/- mice. Our results showedthat both dihydrohomoplantagin and homoplantaginin inhibited apoptosis and the increased level of ICAM-1 and VCAM-1 in oxLDL-stimulated HUVECs and the plaque endothelium of apoE-/- mice. Additionally, both of them restricted atherosclerosis development of apoE-/- mice. Mechanistic studies showed that oxLDL-induced the increase in ROS production, phosphorylation of ERK and nuclear translocation of NF-κB in HUVECs was significantly inhibited by the compounds. Meanwhile, these two compounds promoted Nrf2 nuclear translocation and increased the anti-oxidation downstream HO-1 protein level in HUVECs and plaque endothelium. Notably, knockdown of Nrf2 by siRNA abolished the cell protective effects of compounds and antagonized the inhibition effects of them on ROS production and NF-κB activation in oxLDL-stimulated HUVECs. Collectively, dihydrohomoplantagin and homoplantaginin protected VECs by activating Nrf2 and thus inhibited atherosclerosis in apoE-/- mice.

Biomimetic Metal-Organic Frameworks as Targeted Vehicles to Enhance Osteogenesis.

Although engineered nanoparticles loaded with specific growth factors are used to regulate differentiation of stem cells, the low loading efficiency and biocompatibility are still great challenges in tissue repair. A nature-inspired biomimetic delivery system with targeted functions is attractive for enhancing cell activity and controlling cell fate. Herein, a stem cell membrane (SCM)-wrapped dexamethasone (DEX)-loaded zeolitic imidazolate framework-8 (ZIF-8) is constructed, which integrates the synthetic nanomaterials with native plasma membrane, to achieve efficient DEX delivery and DEX-mediated bone repair. The DEX@ZIF-8-SCM enables high DEX loading capacity, modulates the sustained release, and facilitates the specific uptake of mesenchymal stem cells (MSCs), owing to the porous property of ZIF-8 and the innate targeting capability of SCM. The endocytosed DEX@ZIF-8-SCM shows high cytocompatibility and greatly enhances the osteogenic differentiation of MSCs. Furthermore, RNA-sequencing data reveal that the phosphoinositide 3-kinase (PI3K)-Akt signaling pathways are activated and dominantly involved in the accelerated osteogenesis. In the bone defect model, the administrated DEX@ZIF-8-SCM exerts excellent biocompatibility and effectively promotes bone regeneration. Overall, the SCM-derived biomimetic nanoplatform achieves targeted delivery, excellent biosafety, and enhanced osteogenic differentiation and bone repair, which provides a new and valid strategy for treating various tissue injuries.

Stemness Maintenance and Massproduction of Neural Stem Cells on Poly L-Lactic Acid Nanofibrous Membrane Based on Piezoelectriceffect.

Neural stem cells (NSCs) therapy is promising for treating neurodegenerative disorders and neural injuries. However, the limited in vitro expansion, spontaneous differentiation, and decrease in stemness obstruct the acquisition of high quantities of NSCs, restricting the clinical application of cell-based therapies and tissue engineering. This article reports a facile method of promoting NSCs expansion and maintaining stemness using wireless electrical stimulation triggered by piezoelectric nanomaterials. A nanofibrous membrane of poly L-lactic acid (PLLA) is prepared by electrostatic spinning, and the favorable piezoelectric property of PLLA facilitates the freeing of electrons after transformation. These self-powered electric signals generated by PLLA significantly enhance NSCs proliferation. Further, an undifferentiated cellular state is maintained in the NSCs cultured on the surfaces of PLLA nanofibers exposed to ultrasonic vibration. In addition, the neural differentiation potencies and functions of NSCs expanded by piezoelectric-driven localized electricity are not attenuated. Moreover, cell stemness can be maintained by wireless electric stimulation. Taken together, the electronic signals mediated by PLLA nanofibers facilitate NSCs proliferation. This efficient and simple strategy can maintain the stemness of NSCs during proliferation, which is essential for their clinical application, and opens up opportunities for the mass production of NSCs for use in cell therapy.

Regulation of Neural Differentiation of ADMSCs using Graphene-Mediated Wireless-Localized Electrical Signals Driven by Electromagnetic Induction.

Although adipose-derived mesenchymal stem cells (ADMSCs) isolated from patients' fat are considered as the most important autologous stem cells for tissue repair, significant difficulties in the neural differentiation of ADMSCs still impede stem cell therapy for neurodegenerative diseases. Herein, a wireless-electrical stimulation method is proposed to direct the neural differentiation of ADMSCs based on the electromagnetic effect using a graphene film as a conductive scaffold. By placing a rotating magnet on the top of a culture system without any inducer, the ADMSCs cultured on graphene differentiate into functional neurons within 15 days. As a conductive biodegradable nanomaterial, graphene film acts as a wireless electrical signal generator driven by the electromagnetic induction, and millivolt-level voltage generated in situ provokes ADMSCs to differentiate into neurons, proved by morphological variation, extremely high levels of neuron-specific genes, and proteins. Most importantly, Ca2+ intracellular influx is observed in these ADMSC-derived neurons once exposure to neurotransmitters, indicating that these cells are functional neurons. This research enhances stem cell therapy for neurodegenerative diseases using autologous ADMSCs and overcomes the lack of neural stem cells. This nanostructure-mediated physical-signal simulation method is inexpensive, safe, and localized, and has a significant impact on neural regeneration.

Electroactive Hydroxyapatite/Carbon Nanofiber Scaffolds for Osteogenic Differentiation of Human Adipose-Derived Stem Cells.

Traditional bone defect treatments are limited by an insufficient supply of autologous bone, the immune rejection of allogeneic bone grafts, and high medical costs. To address this medical need, bone tissue engineering has emerged as a promising option. Among the existing tissue engineering materials, the use of electroactive scaffolds has become a common strategy in bone repair. However, single-function electroactive scaffolds are not sufficient for scientific research or clinical application. On the other hand, multifunctional electroactive scaffolds are often complicated and expensive to prepare. Therefore, we propose a new tissue engineering strategy that optimizes the electrical properties and biocompatibility of carbon-based materials. Here, a hydroxyapatite/carbon nanofiber (HAp/CNF) scaffold with optimal electrical activity was prepared by electrospinning HAp nanoparticle-incorporated polyvinylidene fluoride (PVDF) and then carbonizing the fibers. Biochemical assessments of the markers of osteogenesis in human adipose-derived stem cells (h-ADSCs) cultured on HAp/CNF scaffolds demonstrate that the material promoted the osteogenic differentiation of h-ADSCs in the absence of an osteogenic factor. The results of this study show that electroactive carbon materials with a fibrous structure can promote the osteogenic differentiation of h-ADSCs, providing a new strategy for the preparation and application of carbon-based materials in bone tissue engineering.

Endowing Polyetheretherketone Implants with Osseointegration Properties: In Situ Construction of Patterned Nanorod Arrays.

Polyetheretherketone (PEEK) is widely used in orthopedic and craniomaxillofacial surgeries as it exhibits excellent biocompatibility, mechanical property, and chemical stability. However, its clinical application is limited by the biological inertness of PEEK. Numerous efforts have been made to improve the bioactivity of this polymer over the years. However, modification methods that can not only promote osteogenesis but also maintain excellent properties are still limited. Hence, a facile hot die formation technique is developed for establishing patterned nanorod arrays on the PEEK surface in situ. This method can maintain the excellent properties of PEEK and can be used in implantation as it can facilitate osteogenic activity in the absence of any organic/inorganic differentiation-inducing factors. PEEK with 200-nm patterned nanorod arrays on the surface exhibits excellent osteogenic properties. This result is obtained by assessing the osteogenic differentiation properties of rat adipose-derived stem cells at the gene and protein levels in vitro. In vivo experimental results reveal that the surface-modified cylindrical PEEK 200 implants present with excellent osseointegration properties. Moreover, they can tightly bind with the surrounding bone tissue. A practical method for manufacturing single-component PEEK implants with excellent osseointegration properties is reported, and the materials can be possibly used as orthopedic implants.

Regulation of stem cell fate using nanostructure-mediated physical signals.

One of the major issues in tissue engineering is regulation of stem cell differentiation toward specific lineages. Unlike biological and chemical signals, physical signals with adjustable properties can be applied to stem cells in a timely and localized manner, thus making them a hot topic for research in the fields of biomaterials, tissue engineering, and cell biology. According to the signals sensed by cells, physical signals used for regulating stem cell fate can be classified into six categories: mechanical, light, thermal, electrical, acoustic, and magnetic. In most cases, external macroscopic physical fields cannot be used to modulate stem cell fate, as only the localized physical signals accepted by the surface receptors can regulate stem cell differentiation via nanoscale fibrin polysaccharide fibers. However, surface receptors related to certain kinds of physical signals are still unknown. Recently, significant progress has been made in the development of functional materials for energy conversion. Consequently, localized physical fields can be produced by absorbing energy from an external physical field and subsequently releasing another type of localized energy through functional nanostructures. Based on the above concepts, we propose a methodology that can be utilized for stem cell engineering and for the regulation of stem cell fate via nanostructure-mediated physical signals. In this review, the combined effect of various approaches and mechanisms of physical signals provides a perspective on stem cell fate promotion by nanostructure-mediated physical signals. We expect that this review will aid the development of remote-controlled and wireless platforms to physically guide stem cell differentiation both in vitro and in vivo, using optimized stimulation parameters and mechanistic investigations while driving the progress of research in the fields of materials science, cell biology, and clinical research.

Triptolide is a Promising Therapeutic Approach in Treating Thyroid Cancer Based on in silico and in vitro Experiment.

INTRODUCTION: Thyroid cancer is a familiar kind of cancer. Natural products are promising therapeutic approaches in treating thyroid cancer. Triptolide is a diterpenoid epoxide extracted from Tripterygium wilfordii. The mechanism of triptolide in the treatment of thyroid cancer has not been investigated clearly. METHODS: We evaluated triptolide targets and thyroid cancer targets with related databases. The protein-protein interaction (PPI) networks of the triptolide targets and thyroid cancer targets were constructed with Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the core PPI network were obtained. Molecular docking analysis was used to evaluated the binding of triptolide with core targets. Furthermore, apoptosis assays, real-time polymerase chain reaction (RT-PCR) and Western blotting were used to evaluate the anticancer functions of triptolide. RESULTS: Triptolide had 34 targets, and thyroid cancer had 210 targets. The core PPI network of merged PPI networks had 164 nodes and 4513 edges. GO and KEGG enrichment analyses showed that triptolide were related to the cell cycle, apoptosis, and inflammatory signaling pathways. Molecular docking analysis showed that triptolide directly reacted with four core targets: cyclin-dependent kinase inhibitor 1A (CDKN1A), c-JUN, RELA, and tumor protein p53 (TP53). CB-Dock analysis indicated that triptolide could stably bind to core targets. Triptolide inhibited the growth but induced apoptosis of thyroid cancer cells. Triptolide increased the mRNA expression of CDKN1A and TP53 but reduced the mRNA expression of c-JUN and RELA, as shown by RT-PCR. Triptolide increased the protein levels of CDKN1A and phospho-p53 but reduced those of phospho-c-JUN and phospho-NF-κB p65, as shown by Western blotting. DISCUSSION: We considered that triptolide could treat thyroid cancer by inhibiting cell proliferation, inducing apoptosis and inhibiting inflammatory pathways such as the NF-κB and MAPK signaling pathways. CDKN1A, c-JUN, RELA, and TP53 were involved in the antithyroid cancer mechanism of triptolide.