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Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1

  • Ying Li , Yuan Zhang , Wei Lu , Yun Chen and Xiaoling Qian EMAIL logo
Published/Copyright: August 5, 2025
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Open Life Sciences
From the journal Open Life Sciences Volume 20 Issue 1

Abstract

Metastasis remains a major challenge to improve the survival of patients with hepatocellular carcinoma (HCC). Artesunate is an antimalarial drug that also has anti-cancer properties. Additionally, O-GlcNAcylation has been implicated in cancer progression. In this study, we investigated whether artesunate regulated HCC cell migration and invasion and explored its impact on protein O-GlcNAcylation. Cellular functions, including viability, migration, and invasion, were evaluated using the cell counting kit-8, scratch assay, and Transwell analysis. Molecular docking and biolayer interferometry were employed to assess the binding interaction between artesunate and OGA. Furthermore, the O-GlcNAcylation of ZEB1 was examined using immunoprecipitation, cycloheximide chase assay, and immunoblotting. Our results demonstrated that artesunate significantly inhibited HCC cell viability, migration, and invasion. OGA expression was increased in HCC cells after artesunate treatment. Artesunate directly bound to OGA, and OGA knockdown reversed the inhibition of malignant behaviors induced by artesunate. Additionally, OGA suppressed the O-GlcNAcylation of ZEB1 at the Ser670 site, decreasing protein stability. Knockdown of ZEB1 inhibited HCC cellular behaviors. In conclusion, artesunate inhibits HCC cell migration and invasion by binding to OGA, which removes the O-GlcNAcylation of ZEB1 at the Ser670 site. These findings provide a new action mechanism for artesunate to treat HCC.

Graphical abstract

Artesunate combines with OGA, which promotes O-GlcNAcylation of ZEB1 and thus reduces the protein stability of ZEB1, further inhibiting migration and invasion of hepatocellular carcinoma cells.

Keywords: hepatocellular carcinoma; artesunate; OGA; O-GlcNAcylation; ZEB1; migration; invasion

1 Introduction

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide [1]. In addition to genetic predisposition, major risk factors for HCC include hepatitis virus infection, cirrhosis, and non-alcoholic fatty liver disease [2,3]. Early diagnosis plays a critical role in the treatment and prognosis of HCC, as it enables the detection of tumors at a curable stage [4]. However, the majority of patients are diagnosed at advanced stages of the disease. Distant metastasis is a key factor contributing to the poor survival rates observed in advanced HCC patients. Current therapeutic strategies, such as hepatectomy, liver transplantation, and thermal ablation, exhibit limited efficacy in these cases [5]. Furthermore, HCC recurrence rates remain alarmingly high, with up to 70% of patients experiencing recurrence within 5 years post-treatment [6]. Sorafenib remains the only approved systemic therapy for advanced HCC. While targeted therapies and immunotherapies have shown promise in improving survival rates, their clinical efficacy remains inadequately supported by robust evidence [7]. Therefore, a deeper understanding of the molecular mechanisms underlying HCC metastasis is essential to develop novel and effective therapeutic interventions.

Artesunate, a sesquiterpene lactone derivative of artemisinin, has been chemically modified to enhance solubility, absorption, and pharmacokinetic properties, thereby overcoming artemisinin resistance. It is widely used for the treatment of moderate to severe malaria [8,9]. Beyond its antimalarial properties, artesunate exhibits a broad spectrum of biological activities, including antiviral, anti-inflammatory, antitumor, and immunomodulatory effects [10]. Recent studies have highlighted its potential therapeutic applications in respiratory diseases, autoimmune disorders, COVID-19, and various malignancies [11,12,13,14]. Specifically, artesunate has been shown to enhance the sensitivity of HCC cells to sorafenib [15,16] and significantly reduce tumor burden in HCC models [17]. However, the precise molecular mechanisms by which artesunate exerts its antitumor effects in HCC remain poorly understood.

O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is a dynamic and reversible post-translational modification that plays a critical role in regulating various pathophysiological processes. This modification is catalyzed by O-GlcNAc transferase (OGT), which adds O-linked N-acetylglucosamine to serine and threonine residues of target proteins, while O-GlcNAcase (OGA) removes this modification [18]. O-GlcNAcylation is essential for modulating enzyme activity, protein localization, protein–protein interactions, and protein degradation. Dysregulation of O-GlcNAcylation has been implicated in the development and progression of numerous diseases, particularly cancers [19,20]. In HCC, O-GlcNAcylation has been shown to influence tumor growth, metastasis, stemness, and drug resistance [21]. Therefore, a deeper understanding of the regulatory mechanisms of O-GlcNAcylation in HCC is crucial for elucidating the molecular basis of HCC pathogenesis.

In this study, we explored the effects of artesunate on HCC cell migration and invasion and investigated the underlying molecular mechanisms through in vitro experiments. Our findings demonstrate that artesunate significantly inhibits these malignant phenotypes. Furthermore, we provide evidence that artesunate exerts its antitumor effects by modulating OGA-mediated O-GlcNAcylation of ZEB1, a key transcription factor involved in cancer progression.

2 Materials and methods

2.1 Cell culture

The human liver epithelial cell line (THLE3) and one HCC cell line (Hep3B) were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA). An additional HCC cell line, HCCLM3, was procured from the Delf Cell Bank (hfwanwu, Hefei, China). THLE3 cells were cultured in Roswell Park Memorial Institute-1640 medium (GIBCO BRL, Grand Island, NY, USA) supplemented with 10% fetal bovine serum (FBS; GIBCO BRL) and maintained at 37°C in a humidified atmosphere containing 5% CO2. HCC cells (Hep3B and HCCLM3) were cultured in Dulbecco’s Modified Eagle’s Medium (GIBCO BRL) supplemented with 10% FBS under the same conditions (37°C, 5% CO2).

2.2 Determination of cell viability

All cells were seeded into 96-well plates at a density of approximately 2,000 cells per well. Following cell attachment, they were treated with a gradient of artesunate concentrations (0, 25, 50, 100, and 200 μM; MedChemExpress, Monmouth Junction, NJ, USA; Figure 1a) for 48 h. After treatment, 10 μL of cell counting kit-8 solution (Dojindo, Kumamoto, Japan) was added to each well, and the cells were incubated for an additional 2 h. The absorbance at 450 nm was measured using a microplate reader to assess cell viability.

Figure 1 Artesunate inhibits HCC cell viability. (a) Chemical structure of artemisinin. (b) Normal THLE3, (c) Hep3B, and (d) HCCLM3 cells were treated with 0, 25, 50, 100, and 200 μM artesunate for 48 h, and cell viability was measured using the cell counting kit-8. *P < 0.05, **P < 0.01, and ***P < 0.001 vs the 0 μM group.
Figure 1

Artesunate inhibits HCC cell viability. (a) Chemical structure of artemisinin. (b) Normal THLE3, (c) Hep3B, and (d) HCCLM3 cells were treated with 0, 25, 50, 100, and 200 μM artesunate for 48 h, and cell viability was measured using the cell counting kit-8. *P < 0.05, **P < 0.01, and ***P < 0.001 vs the 0 μM group.

2.3 Wound healing assay

HCC cells were seeded into 24-well plates and cultured until they reached a confluent monolayer. A uniform wound was created in the monolayer using a sterile 20 μL pipette tip. After washing with phosphate-buffered saline (PBS), the cells were imaged to establish the baseline (0 h). The plates were then incubated at 37°C with 5% CO2 for 24 h, after which the cells were imaged again to assess wound closure (24 h).

2.4 Transwell assay

Transwell chambers (24-well, pore size: 8 μm; Corning, Corning, NY, USA) were used to assess cell invasion and migration. For invasion assays, the chambers were pre-coated with Matrigel, while uncoated chambers were used for migration assays. A cell suspension containing approximately 1 × 105 cells was added to the upper chamber, and the lower chamber was filled with complete medium. The chambers were incubated at 37°C for 24 h. After incubation, cells that had invaded or migrated through the membrane were fixed, stained with 0.1% crystal violet, and visualized under a light microscope.

2.5 Immunoblotting

HCC cells were lysed using radioimmunoprecipitation assay buffer (Beyotime, Shanghai, China). Protein concentrations were quantified, and equal amounts of protein were separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequently transferred onto polyvinylidene difluoride membranes (Millipore, Billerica, MA, USA). The membranes were blocked with 5% skim milk for 1 h at room temperature and then incubated overnight at 4°C with primary antibodies, followed by incubation with a horseradish peroxidase (HRP)-conjugated secondary antibody for 1 h at room temperature. Protein bands were visualized using BeyoECL Plus solution (Beyotime).

The primary antibodies used in this study included anti-O-GlcNAc/RL2 (ab2739, Abcam, Cambridge, UK), anti-OGA (ab68522, Abcam), anti-OGT (sc-74546, Santa Cruz Biotechnology, Santa Cruz, CA, USA), anti-ZEB1 (ab181451, Abcam), and anti-GAPDH (ab8245, Abcam). The secondary antibody was HRP-conjugated rabbit anti-mouse IgG (ab6728, Abcam).

2.6 Biolayer interferometry (BLI)

BLI experiment was performed using the OCTET RED R8 system (Sartorius, Göttingen, Germany) by a standard protocol as previously described [22]. OGA protein was loaded on NTA biosensors using the following conditions: baseline 1,300 s and loading 3,600 s. Different concentrations of artesunate were prepared using PBS containing 5% dimethyl sulfoxide (DMSO). Subsequently, 200 μL of each artesunate solution was transferred to a 96-well black polypropylene plate containing PBS with 5% DMSO. Binding interactions were monitored in real-time using the OCTET RED R8 instrument, and data were analyzed using Octet Data Analysis 10.0 software.

2.7 Molecular docking

The molecular structure of artesunate was obtained from the PubChem database and converted into the appropriate format using Chem3D. The crystal structure of OGA was retrieved from the RCSB PDB. The crystal water removed, hydrogen atoms added, and energy minimized were performed using the Protein Preparation Wizard on the Maestro 11.9 platform. Molecular docking was performed using the Schrödinger Maestro software through the Glide module. Standard precision flexible ligand mode was used to dock the protein and ligands. The binding compound was visualized using Pymol2.1 software.

2.8 Cell transfection

Hep3B and HCCLM3 cells were seeded into six-well plates and cultured for 24 h prior to transfection. Short hairpin RNA targeting OGA (shOGA), shZEB1, non-targeting control shRNA (shNC), OGA overexpression vector, and empty vector (GenePharma, Shanghai, China) were transfected into HCC cells using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. After 6 h of transfection, the medium was replaced with fresh complete medium. Cells were harvested 48 h post-transfection for subsequent analyses.

2.9 Quantitative real-time polymerase chain reaction (qRT-PCR)

TRIzol reagent was used to isolate total RNA from cells. RNA concentration was determined using the Nanodrop 8000. Total RNA (about 1 μg) was reverse transcribed to cDNA using the PrimeScript 1st strand cDNA synthesis kit (Takara, Dalian, China). Real-time PCR was carried out using FastStart Universal SYBR Green master mix (Roche, Basel, Switzerland) on the LightCycler 480 instrument (Roche). The Ct value was obtained and the results were calculated using the 2−ΔΔCt method. GAPDH served as the internal control. The primers with the following sequences were used in real-time PCR: OGA sense: 5′-CATAGGATGTTTTGGCGAGAGAT-3′ and anti-sense: 5′-GGTGAGATCGCATAGATGAACTC-3′ and GAPDH sense: 5′-CTGGGCTACACTGAGCACC-3′ and anti-sense: 5′-AAGTGGTCGTTGAGGGCAATG-3′.

2.10 Immunoprecipitation

The O-GlcNAcylation levels of proteins were assessed using an immunoprecipitation kit (Beyotime, Shanghai, China) followed by immunoblotting. Briefly, Hep3B cells were lysed in lysis buffer supplemented with a protease inhibitor cocktail, and the lysate was clarified by centrifugation at 14,000 × g for 5 min. Protein A/G magnetic beads were incubated with 500 μL of antibody working solution (targeting N-cadherin, Vimentin, MMP3, MMP9, ZEB1, E-cadherin, and ZO-1) or normal IgG working solution at room temperature for 1 h. The clarified lysate was then incubated with the antibody-beads complex at room temperature for 2 h. After incubation, the magnetic beads were separated and washed three times with lysis buffer. The O-GlcNAcylation levels of the immunoprecipitated proteins were analyzed by immunoblotting using an anti-O-GlcNAc (RL2) antibody.

2.11 Cycloheximide (CHX) chase experiment

To assess the effect of OGA on ZEB1 protein stability, transfected cells were treated with 100 μM CHX for 0, 6, 12, and 24 h. To inhibit OGA activity, cells were treated with 10 μM Thiamet-G (TMG; Sigma-Aldrich, St. Louis, MO, USA). After treatment, cells were harvested, and ZEB1 protein levels were analyzed by immunoblotting. GAPDH was used as an internal loading control for normalization.

2.12 O-GlcNAcylation site prediction

The DictyOGlyc 1.1 server online database was used to predict possible O-GlcNAcylation sites in ZEB1.

2.13 Statistical analysis

Data were acquired from three independent repeated experiments and analyzed using the GraphPad Prism 8.0 software. The results were expressed as mean ± standard deviation. Comparisons were performed using Student’s t-test (two groups) and one-way analysis of variance (three groups). P < 0.05 was considered statistically significant.

3 Results

3.1 Artesunate inhibits HCC cell viability

To evaluate the effects of artesunate on HCC progression, Hep3B and HCCLM3 cells were treated with increasing concentrations of artesunate. THLE3 cells, a non-tumorigenic liver epithelial cell line, were also treated with artesunate as a control. The results demonstrated that artesunate had no significant impact on the viability of THLE3 cells (Figure 1b). In contrast, artesunate significantly reduced the viability of Hep3B and HCCLM3 cells in a dose-dependent manner (Figure 1c and d). According to the cell viability results, the IC50 value was determined. We found IC50 = 745.0 μM in THLE3 cells, IC50 = 98.5 μM in Hep3B cells, and IC50 = 129.9 μM in HCCLM3 cells (Figure S1). Based on these findings, 100 μM artesunate, the lowest concentration that exerted a pronounced inhibitory effect on cell viability, was selected for subsequent experiments.

3.2 Artesunate suppresses migration and invasiveness of HCC cells

Tumor cell migration and invasion are critical processes underlying tumor metastasis. To investigate the effects of artesunate on these phenotypes, scratch wound healing and Transwell assays were performed. The results revealed that artesunate significantly reduced the percentage of wound closure and the number of migrated cells (Figure 2a and c), indicating its inhibitory effect on HCC cell migration. Furthermore, artesunate treatment markedly decreased the number of invaded Hep3B and HCCLM3 cells (Figure 2b). Collectively, these findings demonstrate that artesunate effectively suppresses both migration and invasion of HCC cells.

Figure 2 Artesunate suppresses the cell migration and invasiveness of HCC cells. Hep3B and HCCLM3 cells were treated with artemisinin, and (a) cell migration was measured using the wound healing assay; the Transwell assay was conducted to determine (b) cell invasion and (c) migration. ***P < 0.001 vs the control group.
Figure 2

Artesunate suppresses the cell migration and invasiveness of HCC cells. Hep3B and HCCLM3 cells were treated with artemisinin, and (a) cell migration was measured using the wound healing assay; the Transwell assay was conducted to determine (b) cell invasion and (c) migration. ***P < 0.001 vs the control group.

3.3 Artesunate inhibits OGA-mediated O-GlcNAcylation

O-GlcNAcylation has been implicated in the initiation, progression, and metastasis of HCC [22]. To elucidate the molecular mechanisms underlying the effects of artesunate, we investigated its impact on protein O-GlcNAcylation. As shown in Figure 3a, total O-GlcNAcylation levels were significantly elevated in Hep3B and HCCLM3 cells compared to THLE3 cells. OGT and OGA, the enzymes responsible for the addition and removal of O-GlcNAc modifications, respectively, were also examined. We observed that OGT levels were upregulated, while OGA levels were downregulated in HCC cells relative to THLE3 cells (Figure 3a). Further immunoblotting analysis revealed that artesunate treatment reduced total O-GlcNAcylation levels and increased OGA expression, but had no effect on OGT levels (Figure 3b). Biolayer interferometry (BLI) demonstrated strong binding between artesunate and OGA (Figure 3c), and molecular docking analysis further confirmed this interaction (Figure 3d–f). These findings collectively suggest that artesunate suppresses O-GlcNAcylation in HCC by directly binding to OGA.

Figure 3 Artesunate inhibits OGA-mediated O-GlcNAcylation. (a) Immunoblotting was performed to detect the total O-GlcNAcylation level and protein levels of OGT and OGA. (b) The effect of artesunate on the total O-GlcNAcylation level and protein levels of OGT and OGA was evaluated using immunoblotting. (c) BLI analysis of the binding between artesunate and OGA. (d) The 3D structure of artesunate and the OGA binding complex was acquired using molecular docking. (e) The electrostatic surface of the protein OGA. (f) The detailed binding mode of artesunate and OGA.
Figure 3

Artesunate inhibits OGA-mediated O-GlcNAcylation. (a) Immunoblotting was performed to detect the total O-GlcNAcylation level and protein levels of OGT and OGA. (b) The effect of artesunate on the total O-GlcNAcylation level and protein levels of OGT and OGA was evaluated using immunoblotting. (c) BLI analysis of the binding between artesunate and OGA. (d) The 3D structure of artesunate and the OGA binding complex was acquired using molecular docking. (e) The electrostatic surface of the protein OGA. (f) The detailed binding mode of artesunate and OGA.

3.4 Artesunate hampers HCC cell migration and invasion via increasing OGA expression

To determine whether OGA regulates HCC cellular behaviors, shOGA and shNC were transfected into Hep3B and HCCLM3 cells. OGA expression was significantly reduced in shOGA-transfected cells compared to shNC-transfected cells (Figure 4a). Artesunate treatment inhibited cell viability; however, this effect was attenuated by OGA knockdown (Figure 4b). Similarly, artesunate suppressed cell migration and invasion, but these inhibitory effects were reversed in OGA-depleted cells (Figure 4c–f). These results demonstrate that silencing OGA counteracts the artesunate-induced suppression of cell viability, migration, and invasion in HCC cells.

Figure 4 Artesunate hampers HCC cell migration and invasion via increasing OGA expression. (a) OGA mRNA expression was measured in Hep3B and HCCLM3 cells transfected with shNC and shOGA using qRT-PCR. (b) HCC cells were treated with artesunate and transfected with shOGA; cell viability was assessed using the cell counting kit-8. (c) Quantification results of the wound healing assay. (d) Represent images of wound healing and Transwell assays. (e) Cell invasion and (f) migration analyzed using the Transwell assay were quantified. ***P < 0.001 vs the shNC group. ### P < 0.001 vs the artesunate + shNC group.
Figure 4

Artesunate hampers HCC cell migration and invasion via increasing OGA expression. (a) OGA mRNA expression was measured in Hep3B and HCCLM3 cells transfected with shNC and shOGA using qRT-PCR. (b) HCC cells were treated with artesunate and transfected with shOGA; cell viability was assessed using the cell counting kit-8. (c) Quantification results of the wound healing assay. (d) Represent images of wound healing and Transwell assays. (e) Cell invasion and (f) migration analyzed using the Transwell assay were quantified. ***P < 0.001 vs the shNC group. ### P < 0.001 vs the artesunate + shNC group.

3.5 OGA inhibits O-GlcNAcylation of ZEB1

OGA is known to remove O-GlcNAcylation modifications from proteins. To identify potential O-GlcNAc-modified proteins involved in tumor metastasis, we screened several metastasis-related proteins and assessed their O-GlcNAcylation levels. Among these proteins, overexpression of OGA specifically reduced the O-GlcNAcylation levels of ZEB1 (Figure 5a). Furthermore, co-immunoprecipitation assays confirmed that OGA physically interacts with ZEB1 (Figure 5b). Overexpression of OGA decreased ZEB1 protein stability, while inhibition of OGA restored ZEB1 stability (Figure 5c). Bioinformatic analysis predicted multiple potential O-GlcNAcylation sites in ZEB1 (Figure 5d). Among these, the five highest-probability sites were selected for further validation. Mutation of the S670 site significantly reduced O-GlcNAcylation levels and downregulated ZEB1 protein expression compared to WT-ZEB1 (Figure 5e), indicating that S670 is a critical O-GlcNAcylation site. These findings collectively demonstrate that OGA inhibits O-GlcNAcylation of ZEB1 at the S670 site, thereby reducing ZEB1 protein stability.

Figure 5 OGA inhibits O-GlcNAcylation of ZEB1. (a) The effect of OGA on the O-GlcNacylation levels of tumor metastasis-related proteins, including N-cadherin, Vimentin, MMP3, MMP9, ZEB1, E-cadherin, and ZO-1. (b) The interaction between OGA and ZEB1 was assessed using immunoprecipitation. (c) Effect of OGA-mediated O-GlcNAcylation on the stability of ZEB1 protein. (d) Potential O-GlcNAcylation sites in ZEB1 protein. (e) ZEB1 O-GlcNAcylation sites were analyzed using immunoprecipitation and immunoblotting. ***P < 0.001 vs the vector group. ### P < 0.001 vs the OGA group.
Figure 5

OGA inhibits O-GlcNAcylation of ZEB1. (a) The effect of OGA on the O-GlcNacylation levels of tumor metastasis-related proteins, including N-cadherin, Vimentin, MMP3, MMP9, ZEB1, E-cadherin, and ZO-1. (b) The interaction between OGA and ZEB1 was assessed using immunoprecipitation. (c) Effect of OGA-mediated O-GlcNAcylation on the stability of ZEB1 protein. (d) Potential O-GlcNAcylation sites in ZEB1 protein. (e) ZEB1 O-GlcNAcylation sites were analyzed using immunoprecipitation and immunoblotting. ***P < 0.001 vs the vector group. ### P < 0.001 vs the OGA group.

3.6 Knockdown of ZEB1 inhibits migration and invasion of HCC cells

The effect of ZEB1 on cellular processes, we transfected shNC and shZEB1 into Hep3B and HCCLM3 cells. ZEB1 expression was downregulated after shZEB1 transfection, compared with shNC (Figure 6a). Next, we found that knockdown of ZEB1 inhibited HCC cell viability, migration, and invasion (Figure 6b–e). The findings suggest that ZEB1 acts as an oncogene in HCC.

Figure 6 Knockdown of ZEB1 inhibits migration and invasion of HCC cells. (a) ZEB1 mRNA expression was measured in Hep3B and HCCLM3 cells transfected with shNC and shZEB1 using qRT-PCR. After transfection, (b) cell viability was assessed using the cell counting kit-8. (c) Cell migration was evaluated using the wound healing assay, and the percentage of wound healing was quantified. (d) Cell migration was analyzed using. (e) Cell invasion was evaluated using the Transwell assay and quantified. ***P < 0.001 vs the shNC group.
Figure 6

Knockdown of ZEB1 inhibits migration and invasion of HCC cells. (a) ZEB1 mRNA expression was measured in Hep3B and HCCLM3 cells transfected with shNC and shZEB1 using qRT-PCR. After transfection, (b) cell viability was assessed using the cell counting kit-8. (c) Cell migration was evaluated using the wound healing assay, and the percentage of wound healing was quantified. (d) Cell migration was analyzed using. (e) Cell invasion was evaluated using the Transwell assay and quantified. ***P < 0.001 vs the shNC group.

4 Discussion

Artesunate, a well-established antimalarial drug, has garnered increasing attention for its anti-tumor properties. Numerous studies have explored its effects on various cancers, elucidating its mechanisms of action and molecular targets. For instance, artesunate inhibits colorectal cancer cell proliferation by inducing autophagy and disrupting mitochondrial function [23]. In head and neck cancer, artesunate promotes ferroptosis and enhances cisplatin sensitivity [24]. Similarly, in thyroid cancer, artesunate suppresses cell growth, metastasis, and induces apoptosis by inactivating the PI3K/AKT/FKHR pathway [25]. Artesunate has also emerged as a promising therapeutic candidate for HCC. Previous studies have demonstrated its ability to alleviate sorafenib resistance in HCC [15,16,26], potentially enhancing sorafenib efficacy and improving patient outcomes. The mechanisms underlying artesunate’s anti-cancer effects are multifaceted. Chen et al. [27] reported that artesunate induces autophagy by targeting glucosylceramidase, while Jiang et al. [28] highlighted its role in promoting ferroptosis by disrupting iron homeostasis in HCC cells. However, the impact of artesunate on HCC metastasis remains poorly understood. In this study, we demonstrated that artesunate significantly inhibits HCC cell viability, migration, and invasion, suggesting its potential as a therapeutic agent for metastatic HCC. However, we only performed in vitro experiments. Before a preclinical study, an animal study is needed to evaluate the effect of artesunate on tumor growth and metastasis.

Given the critical role of O-GlcNAcylation in cancer progression, we investigated whether artesunate modulates this post-translational modification to exert its anti-tumor effects. Our results revealed that O-GlcNAcylation levels were elevated in HCC cells and significantly reduced following artesunate treatment. Concurrently, artesunate upregulated OGA expression, suggesting that OGA-mediated O-GlcNAcylation plays a key role in the anti-HCC effects of artesunate. OGA is known to be dysregulated in various cancers and is implicated in tumor progression, metastasis, and immune modulation [29]. OGA has been reported to function as a tumor suppressor [30,31], including in HCC. Specifically, downregulation of OGA, mediated by RANBP2, has been shown to enhance O-GlcNAcylation levels, thereby promoting HCC cell viability and invasion [32]. Additionally, astragalus, an active component of Astragalus membranaceus, has been reported to induce HCC cell apoptosis and endoplasmic reticulum stress by upregulating OGA expression [33]. In this study, we demonstrated that artesunate directly binds to OGA and that OGA knockdown reverses the inhibitory effects of artesunate on HCC cell viability, migration, and invasion. These findings collectively indicate that artesunate suppresses HCC progression by upregulating OGA expression and modulating O-GlcNAcylation.

OGA regulates tumor progression by inhibiting the O-GlcNAcylation of substrate proteins. In this study, we identified that ZEB1 undergoes O-GlcNAcylation. As a transcription factor implicated in EMT, ZEB1’s overexpression serves as a predictor of poor survival outcomes in various cancers [34]. Noteworthily, ZEB1 modulates tumor metastasis through its influence on tumor cell motility and dissemination [35]. Extensive research has elucidated the role of ZEB1 in HCC, demonstrating that it acts as a tumor promoter by facilitating metastasis, the Warburg effect, chemoresistance, and impeding tumor cell apoptosis [36,37,38]. Additionally, O-GlcNAcylation of ZEB1 has been shown to promote lipid peroxidation and ferroptosis in pancreatic cancer cells [39]. However, whether ZEB1 is subject to O-GlcNAcylation in HCC remains unclear. O-GlcNAcylation has been reported to contribute to protein structure and functions, including localization, stability, and chromatin remodeling [40]. Our findings reveal that OGA specifically inhibits O-GlcNAcylation of ZEB1 at the S670 site, thereby promoting its protein degradation, suggesting that O-GlcNAcylation is involved in modulating ZEB1 protein stability, consistent with a previous study [39]. These findings will provide new insights into the role of post-translational modifications of proteins and the regulatory mechanism of ZEB1 in HCC. However, we speculated that O-GlcNAcylation may directly affect ZEB1 protein conformation, either through competitive interaction with other post-translational modifications such as phosphorylation or through the ubiquitin-proteasome pathway affecting ZEB1stability, which will be further studied in our work.

In conclusion, this study demonstrates that artesunate inhibits cell migration and invasion in HCC by enhancing OGA expression, which in turn suppresses the O-GlcNAcylation of ZEB1. These findings suggest that artesunate may represent an effective therapeutic agent for the treatment of HCC and offer novel insights into its mechanism of action.

  1. Funding information: The work was supported by the Zhejiang Provincial Administration of Traditional Chinese Medicine under grant number 2024ZL116.

  2. Author contributions: All authors participated in the design, interpretation of the studies, analysis of the data, and review of the manuscript. Y.L. drafted the work and revised it critically for important intellectual content. Y.Z., W.L., and Y.C. were responsible for the acquisition, analysis, and interpretation of data for the work. Y.L. and X.Q. made substantial contributions to the conception or design of the work. All authors read and approved the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2025-02-06
Revised: 2025-04-03
Accepted: 2025-04-07
Published Online: 2025-08-05

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/biol-2025-1109
Keywords for this article
hepatocellular carcinoma; artesunate; OGA; O-GlcNAcylation; ZEB1; migration; invasion
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  3. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  4. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  5. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  6. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  7. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
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  9. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
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  12. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
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  14. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  15. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  16. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  17. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  18. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  19. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  20. Changes in blood glucose and metabolism in hyperuricemia mice
  21. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  22. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  23. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  24. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  25. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  26. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  27. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  28. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  29. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  30. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  31. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  32. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  33. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  34. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  35. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  36. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  37. Low-pressure exposure influences the development of HAPE
  38. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  39. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  40. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  41. A case of bloodstream infection caused by Neisseria gonorrhoeae
  42. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  43. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  44. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  45. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  46. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  47. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  48. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  49. Sodium butyrate aids brain injury repair in neonatal rats
  50. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  51. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  52. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  53. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  54. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  55. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  56. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  57. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  58. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  59. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  60. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  61. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  62. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  63. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  64. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  65. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  66. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  67. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  68. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  69. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  70. Oncolytic bacteria: A revolutionary approach to cancer therapy
  71. A de novo meningioma with rapid growth: A possible malignancy imposter?
  72. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  73. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  74. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  75. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  76. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  77. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  78. Evaluation and application analysis of animal models of PIPNP based on data mining
  79. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  80. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  81. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  82. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  83. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  84. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  85. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  86. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  87. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  88. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  89. RNF144A and RNF144B: Important molecules for health
  90. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  91. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  92. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  93. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  94. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  95. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  96. Understanding risk factors and prognosis in diabetic foot ulcers
  97. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  98. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  99. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  100. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  101. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  102. Pulmonary cryptococcosis with headache as the first presentation: A case report
  103. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  104. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  105. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  106. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  107. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  108. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  109. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  110. Wound healing and signaling pathways
  111. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  112. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  113. Research progress on the impact of curcumin on immune responses in breast cancer
  114. Biogenic Cu/Ni nanotherapeutics from Descurainia sophia (L.) Webb ex Prantl seeds for the treatment of lung cancer
  115. Dapagliflozin attenuates atrial fibrosis via the HMGB1/RAGE pathway in atrial fibrillation rats
  116. Glycitein alleviates inflammation and apoptosis in keratinocytes via ROS-associated PI3K–Akt signalling pathway
  117. ADH5 inhibits proliferation but promotes EMT in non-small cell lung cancer cell through activating Smad2/Smad3
  118. Apoptotic efficacies of AgNPs formulated by Syzygium aromaticum leaf extract on 32D-FLT3-ITD human leukemia cell line with PI3K/AKT/mTOR signaling pathway
  119. Novel cuproptosis-related genes C1QBP and PFKP identified as prognostic and therapeutic targets in lung adenocarcinoma
  120. Bee venom promotes exosome secretion and alters miRNA cargo in T cells
  121. Treatment of pure red cell aplasia in a chronic kidney disease patient with roxadustat: A case report
  122. Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status
  123. Kynurenine facilitates renal cell carcinoma progression by suppressing M2 macrophage pyroptosis through inhibition of CASP1 cleavage
  124. RFX5 promotes the growth, motility, and inhibits apoptosis of gastric adenocarcinoma cells through the SIRT1/AMPK axis
  125. ALKBH5 exacerbates early cardiac damage after radiotherapy for breast cancer via m6A demethylation of TLR4
  126. Phytochemicals of Roman chamomile: Antioxidant, anti-aging, and whitening activities of distillation residues
  127. Circadian gene Cry1 inhibits the tumorigenicity of hepatocellular carcinoma by the BAX/BCL2-mediated apoptosis pathway
  128. The TNFR-RIPK1/RIPK3 signalling pathway mediates the effect of lanthanum on necroptosis of nerve cells
  129. Longitudinal monitoring of autoantibody dynamics in patients with early-stage non-small-cell lung cancer undergoing surgery
  130. The potential role of rutin, a flavonoid, in the management of cancer through modulation of cell signaling pathways
  131. Construction of pectinase gene engineering microbe and its application in tobacco sheets
  132. Construction of a microbial abundance prognostic scoring model based on intratumoral microbial data for predicting the prognosis of lung squamous cell carcinoma
  133. Sepsis complicated by haemophagocytic lymphohistiocytosis triggered by methicillin-resistant Staphylococcus aureus and human herpesvirus 8 in an immunocompromised elderly patient: A case report
  134. Sarcopenia in liver transplantation: A comprehensive bibliometric study of current research trends and future directions
  135. Advances in cancer immunotherapy and future directions in personalized medicine
  136. Can coronavirus disease 2019 affect male fertility or cause spontaneous abortion? A two-sample Mendelian randomization analysis
  137. Heat stroke associated with novel leukaemia inhibitory factor receptor gene variant in a Chinese infant
  138. PSME2 exacerbates ulcerative colitis by disrupting intestinal barrier function and promoting autophagy-dependent inflammation
  139. Hyperosmolar hyperglycemic state with severe hypernatremia coexisting with central diabetes insipidus: A case report and literature review
  140. Efficacy and mechanism of escin in improving the tissue microenvironment of blood vessel walls via anti-inflammatory and anticoagulant effects: Implications for clinical practice
  141. Merkel cell carcinoma: Clinicopathological analysis of three patients and literature review
  142. Ecology and Environmental Science
  143. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  144. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  145. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  146. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  147. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  148. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  149. Global assessment of the fate of nitrogen deposition in forest ecosystems: Insights from 15N tracer studies
  150. Fungal and bacterial pathogenic co-infections mainly lead to the assembly of microbial community in tobacco stems
  151. Influencing of coal industry related airborne particulate matter on ocular surface tear film injury and inflammatory factor expression in Sprague-Dawley rats
  152. Temperature-dependent development, predation, and life table of Sphaerophoria macrogaster (Thomson) (Diptera: Syrphidae) feeding on Myzus persicae (Sulzer) (Homoptera: Aphididae)
  153. Eleonora’s falcon trophic interactions with insects within its breeding range: A systematic review
  154. Agriculture
  155. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  156. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  157. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  158. Molecular mechanism of follicular development in laying hens based on the regulation of water metabolism
  159. Animal Science
  160. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  161. Plant Sciences
  162. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  163. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  164. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  165. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  166. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  167. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  168. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  169. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  170. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  171. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  172. Using plant electrical signals of water hyacinth (Eichhornia crassipes) for water pollution monitoring
  173. Food Science
  174. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  175. Review on role of honey in disease prevention and treatment through modulation of biological activities
  176. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  177. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  178. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  179. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  180. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  181. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  182. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  183. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  184. The dilemma of food genetics and improvement
  185. Bioengineering and Biotechnology
  186. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  187. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  188. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  189. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  190. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  191. Corrigendum
  192. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  193. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
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