Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025048
As a classic tumor suppressor gene, p53 has been extensively studied since its discovery in the mid-1980s. Research findings have revealed that p53 protein expression is suppressed in various cancers [1]. For example, in cervical cancer, p53 predominantly exists in a wild-type form to maintain its biological function [2]. Nevertheless, its tumor-suppressive activity is significantly impaired because of rapid protein degradation, short half-life, and low levels. Post-translational modifications (PTMs) of p53, such as ubiquitination, acetylation, phosphorylation and methylation, are critical regulators of its stability, activity, conformation, localization, and interactions with cofactors [3]. Among these, ubiquitination and acetylation play central roles in controlling p53 protein stability and activity [4]. Therefore, targeting p53 PTMs to modulate its ubiquitination and acetylation levels represents an effective strategy to increase its stability and tumor-suppressive function, offering a promising avenue for cervical cancer drug development. In 99% of cervical cancers (high-risk human papillomavirus-positive), E3 ubiquitin ligase E6-associated protein (E6AP) mediates the ubiquitination degradation of p53 [5], whereas histone deacetylase 6 (HDAC6) deacetylates p53. In this study, we explored the possibility of combining the natural product withferin A (WA) with the HDAC6 inhibitor ricolinostat (RIC) to treat cervical cancer cells, with a focus on the ubiquitination and acetylation of p53 and the consequences for its stability. These results suggested that the combination of WA and RIC is more effective than either treatment alone in inhibiting the degradation and increasing the stability of p53, thereby synergistically slowing the onset and progression of cervical cancer.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025193
Arsenic, a toxic metalloid, exists in organic or inorganic states within the Earth’s seawater, river water, soil, atmosphere, food sources, and diverse biological tissues [1]. It poses a threat to the health of hundreds of millions of people globally [2]. Arsenic exposure has toxic effects on the cardiovascular system of organisms, thus endangering human health [3]. Research has indicated that the harmful effect of arsenic exposure on the heart is associated with abnormal calcium handling in myocardial cells [4]. The cardiac ryanodine receptor type 2 (RyR2) is a primary channel involved in the surface of the endoplasmic reticulum in cardiac myocytes that regulates the release of Ca2+ during the systolic phase [5]. The integrity of its function is crucial for maintaining calcium homeostasis in cardiac myocytes. However, when myocardial tissue is damaged and undergoes pathological changes, the spatial structure of the RyR2 protein becomes unstable and becomes excessively activated, thereby triggering Ca2+ leakage [6]. Dantrolene (Dan), which serves as a stabilizer of RyR1, is frequently employed in clinical settings for the treatment of malignant hyperpyrexia and relieves spastic muscle tension [7]. Previous studies have demonstrated that dantrolene also has a stabilizing effect on RyR2 [8]. Research has shown that dantrolene can prevent calcium leakage in myocardial cells by stabilizing the tertiary structure of the RyR2 protein and thereby inhibiting the pathological hyperactivity of RyR2 [9]. Therefore, this study hypothesizes that dantrolene, by virtue of this stabilizing effect, can alleviate myocardial injury caused by arsenic exposure to some extent and plays a role in protecting cardiac function. For this purpose, we established an arsenic exposure model and a Dan intervention arsenic exposure model to verify the protective effect of Dan on the myocardial tissue and cardiac function of arsenic-exposed rats.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024085
Despite the tremendous progress in cancer research over the past few decades, effective therapeutic strategies are still urgently needed. Accumulating evidence suggests that immune checkpoints are the cause of tumor immune escape. PD-1/PD-L1 are among them. Posttranslational modification is the most critical step for protein function, and the regulation of PD-L1 by small molecules through posttranslational modification is highly valuable. In this review, we discuss the mechanisms of tumor cell immune escape and several posttranslational modifications associated with PD-L1 and describe examples in which small molecules can regulate PD-L1 through posttranslational modifications. Herein, we propose that the use of small molecule compounds that act by inhibiting PD-L1 through posttranslational modifications is a promising therapeutic approach with the potential to improve clinical outcomes for cancer patients.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025093
YY1 is a crucial transcription factor and plays significant roles in biological processes. However, the mechanisms of YY1 action in ischemia-reperfusion injury and its regulatory role in ferroptosis have not been extensively studied. This study aims to elucidate the molecular mechanism by which NEDD4L-mediated degradation of YY1 through ubiquitination suppresses SLC7A11 transcription, leading to the promotion of cellular ferroptosis and exacerbation of hepatic ischemia-reperfusion injury (IRI), via the integration of multiple omics sequencing datasets. An IRI-I/R mouse model is established, followed by proteomic sequencing to identify proteins that are differentially expressed during IRI. The altered expression of YY1 is validated, and in vivo and in vitro experiments are used to assess its impact on IRI damage. The E3 ligase NEDD4L, which regulates YY1 ubiquitination, is identified and validated via the UbiBrowser 2.0 database. The ubiquitination types of YY1 and its sites are screened and confirmed through in vitro experiments. Transcriptional sequencing of YY1-overexpressing cell lines is conducted to analyze the involvement of the downstream transcription factor SLC7A11 in IRI, followed by validation of its regulatory role. The results show that YY1 is downregulated in liver tissues during IRI and is expressed primarily in liver cells. YY1 overexpression alleviates liver tissue and liver cell IRI both in vitro and in vivo. Upregulation of E3 ligase expression during IRI promotes the K63-linked ubiquitination of YY1 at the K339 site, leading to proteasomal degradation of YY1. RNA-seq analysis and experimental validation demonstrate that YY1 suppresses IRI-induced ferroptosis via the transcriptional regulation of downstream target genes. YY1 positively regulates SLC7A11 transcription, inhibits IRI-induced ferroptosis and ameliorates liver injury. In summary, the E3 ubiquitin ligase NEDD4L facilitates YY1 protein degradation through ubiquitination, suppressing the transcription of the ferroptosis inhibitor SLC7A11, thus promoting IRI-related ferroptosis and exacerbating liver injury.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024225
Arsenic is widely present in nature, and its compounds are extensively used in industrial, agricultural, and medical fields. Arsenic trioxide (As2O3) is specifically used as a therapeutic agent for acute promyelocytic leukemia because it induces cancer cell differentiation and apoptosis, significantly reduces the cancer cell count and has unique medical value. However, owing to its high toxicity and carcinogenicity, long-term use can induce cardiovascular diseases such as arrhythmia and myocardial contractile dysfunction. However, research on the treatment of arsenic-induced cardiotoxicity remains relatively scarce. Notably, artemisinin has anti-inflammatory and antioxidative effects on various heart diseases, effectively inhibiting reactive oxygen species (ROS) production, preventing myocardial damage and apoptosis caused by arsenic poisoning, and improving cardiac contractile and diastolic functions, thus enhancing cardiac function. This study aims to discuss the impact of artemisinin on the myocardium of arsenic-poisoned rats. Forty 12-week-old male SD rats were randomly divided into five groups: control, arsenic poisoning, drug control, low-dose artemisinin, and high-dose artemisinin. As2O3 was intraperitoneally injected at 5 mg/kg/day for 10 days in the arsenic poisoning, low-dose, and high-dose groups, whereas the control and drug control groups received equal volumes of physiological saline. Artemisinin was subsequently injected at corresponding doses for three weeks. Myocardial contrast echocardiography (MCE) was used to assess myocardial blood perfusion. Blood and myocardial tissue samples were collected for biochemical and histological analyses. Results showed that arsenic poisoning significantly decreased myocardial blood perfusion (AUC and WIS×PI) and increased CD31 expression, indicating microvascular damage and inflammation. Artemisinin intervention, especially at high dose, restored perfusion and reduced CD31 expression, suggesting a protective effect. Electron microscopy confirmed that artemisinin alleviated arsenic-induced myocardial structural damage. These findings suggest that artemisinin alleviates arsenic-induced myocardial injury by modulating oxidative stress and inflammatory responses.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024012
Voltage-dependent anion channel 1 (VDAC1) is a pore protein located in the outer mitochondrial membrane. Its channel gating mediates mitochondrial respiration and cell metabolism, and it has been identified as a critical modulator of mitochondria-mediated apoptosis. In many diseases characterized by mitochondrial dysfunction, such as cancer and neurodegenerative diseases, VDAC1 is considered a promising potential therapeutic target. However, there is limited research on the regulatory factors involved in VDAC1 protein expression in both normal and pathological states. In this study, we find that VDAC1 protein expression is up-regulated in various neuronal cell lines in response to intracellular metabolic and oxidative stress. We further demonstrate that VDAC1 expression is modulated by intracellular ATP level. Through the use of pharmacological agonists and inhibitors and small interfering RNA (siRNA), we reveal that the AMPK/PGC-1α signaling pathway is involved in regulating VDAC1 expression. Additionally, based on bioinformatics predictions and biochemical verification, we identify p53 as a potential transcription factor that regulates VDAC1 promoter activity during metabolic oxidative stress. Our findings suggest that VDAC1 expression is regulated by the AMPK/PGC-1α and p53 pathways, which contributes to the maintenance of stress adaptation and apoptotic homeostasis in neuronal cells.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21366
BACKGROUND: In recent years, the research on stroke rehabilitation robots has developed rapidly both domestically and internationally. It involves the intersection of multiple disciplines such as rehabilitation medicine, artificial intelligence, virtual reality, and sensor technology, and has become a research hotspot in the field of stroke rehabilitation. OBJECTIVE: To grasp the current status and hotspots of research in this field through a comparative analysis of domestic and international studies, and to predict future development trends. METHODS: The Web of Science Core Collection and CNKI databases were selected as data sources to collect relevant literature on stroke rehabilitation robots from 2005 to 2025. CiteSpace 6.2.R3 visualization software and bibliometric methods were used to compare the annual publication volume, countries, and keywords of included studies, analyze differences between domestic and international research, and summarize and prospect frontier technologies. RESULTS AND CONCLUSION: A total of 3,522 English and 717 Chinese articles were included. From 2005 to 2025, 81 countries participated in research, forming a cross-continental cooperation network centered on the United States, China, and Italy. Publication trends showed a yearly increase both domestically and internationally, with an average annual growth rate of 13.06% internationally and 20.17% domestically, the latter being about 1.5 times faster. Research trends indicated that international research has gone through stages of mechanism exploration, clinical translation, and intelligent integration, currently focusing on multidisciplinary intersection and technology integration such as robot perception systems and machine learning. Domestic research started with technology introduction and clinical validation, gradually developing into intelligent integration and precise rehabilitation, with significant progress in multimodal fusion such as brain-computer interfaces and virtual reality in recent years. Research hotspots: international research mainly focuses on design optimization of robot technology and multimodal technology integration, while domestic research emphasizes the impact on functional outcomes after stroke. Additionally, international research is more advanced in neurophysiological signal fusion, advanced algorithms, and model construction, whereas domestic research shows unique advantages in combining rehabilitation technology with traditional Chinese medicine therapies. The results indicate that the field of stroke rehabilitation robots is in a rapid development stage, with technology integration and clinical translation being the core trends for future development. Although domestic and international research have different emphases, both are committed to improving the intelligence, lightweight design, and clinical practicality of rehabilitation robots. Domestic research started later but is developing rapidly, gradually building a multimodal technology system characterized by intelligent integration and precise rehabilitation. In the future, domestic and international research can complement each other, with China contributing clinical big data and application scenarios, and foreign countries providing core technologies and innovative methods, jointly advancing breakthroughs and applications in stroke rehabilitation robot technology.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026046
Epstein-Barr virus-associated gastric cancer (EBVaGC) displays unique clinicopathological hallmarks, yet serology-based tools for its detection are still limited. Here, we develop a functional EBV proteome microarray covering 72 viral proteins and apply it to profile antibody responses in 62 gastric cancer patients. The resulting landscape reveals an IgG-skewed humoral signature specific to EBVaGC and identifies 34 EBV antigens exhibiting differential reactivities. Multivariable logistic regression integrates complementary markers into an optimal five-analyte panel (LF2_IgG, BBLF2_IgG, BLRF2_IgG, BPLF1-2_IgA, and BGLF4_IgA) that achieves outstanding discrimination performance (AUC = 0.93) in an independent validation set (n = 316). The panel’s performance is further validated in a community-based screening cohort (n = 474), where it achieves 87.3% sensitivity and 88.3% specificity for distinguishing EBVaGC from non-malignant gastric conditions spanning gastritis to dysplasia (AUC = 0.94). Together, these results establish a serological framework for EBVaGC diagnosis and provide a scalable strategy for population-level screening that could materially improve the management of this virus-driven malignancy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025093
Hepatic ischemia-reperfusion injury (IRI) remains a major clinical challenge in liver transplantation and resection, with ferroptosis emerging as a critical cell death modality. This study investigates the mechanistic role of the transcription factor YY1 and its regulation by the E3 ubiquitin ligase NEDD4L in hepatic IRI. Using an established mouse IRI model and proteomic sequencing, YY1 was identified as significantly downregulated in injured liver tissues, predominantly in hepatocytes. In vivo and in vitro overexpression of YY1 attenuated IRI-induced liver damage and ferroptosis. Mechanistically, NEDD4L, an E3 ligase upregulated during IRI, was found to interact with YY1 and catalyze K63-linked ubiquitination at lysine 339, leading to proteasomal degradation of YY1. Transcriptomic analysis and validation revealed that YY1 positively regulates the transcription of SLC7A11, a key ferroptosis inhibitor. Consequently, NEDD4L-mediated degradation of YY1 suppresses SLC7A11 expression, promoting ferroptosis and exacerbating hepatic injury. These findings delineate a novel NEDD4L-YY1-SLC7A11 axis in IRI pathogenesis, offering potential therapeutic targets. The study acknowledges limitations, including the need for validation in human liver samples and further in vivo confirmation of some in vitro findings. This research provides a mechanistic framework for developing targeted interventions against hepatic IRI.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025048
Cervical cancer remains a leading cause of cancer-related mortality among women, with high-risk HPV-positive cases constituting 99% of instances. Despite wild-type p53 expression, its tumor-suppressive function is crippled by E6AP-mediated ubiquitination and HDAC6-driven deacetylation, resulting in rapid degradation and low steady-state levels. This study evaluates a combinatorial strategy employing the natural product withaferin A (WA) and the HDAC6 inhibitor ricolinostat (RIC) to simultaneously target p53 ubiquitination and acetylation in HeLa, SiHa, and Caski cervical cancer cells. Dose-response CCK-8 assays established that both agents inhibit proliferation in a dose-dependent manner. Combination treatment significantly reduced cell viability compared to monotherapies, with CompuSyn analysis yielding a combination index (CI) below 1, confirming synergy. Colony formation assays further demonstrated a marked decrease in clonogenic survival. Mechanistically, WA disrupted the p53-E6AP interaction, reducing p53 ubiquitination, while RIC inhibited HDAC6-mediated deacetylation, increasing p53 acetylation. The dual treatment stabilized p53, as evidenced by extended half-life in cycloheximide chase assays. These findings suggest that concurrent modulation of p53 post-translational modifications via WA and RIC offers a potent therapeutic avenue for cervical cancer, meriting further preclinical development.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025057
MEIOB and SPATA22 are gonad-specific proteins essential for meiotic recombination, with mutations linked to oligospermia and azoospermia in human males. The heterodimer recognizes and binds single-stranded DNA (ssDNA) protected by replication protein A (RPA) to promote homologous recombination repair. However, sequence divergence between human and rodent orthologs leads to functional differences. Here, human MEIOB (hMEIOB) and SPATA22 (hSPATA22) were expressed and purified for electrophoretic mobility shift assay (EMSA), magnetic tweezer (MT) assay, and bio-layer interferometry (BLI) to dissect ssDNA binding patterns. hMEIOB alone exhibits low ssDNA-binding affinity and stability, whereas hSPATA22 binds ssDNA faster and more stably, promoting ssDNA condensation. The hMEIOB-hSPATA22 heterodimer displays strong binding affinity and stability. Multiple heterodimers spontaneously aggregate in vitro, with BLI response signals of ~4.31 nm for hSPATA22 alone versus ~19.5 nm for the heterodimer, indicating polymer formation. The hRPA complex weakens the binding affinity of hMEIOB, hSPATA22, and the heterodimer to ssDNA, and binds to hSPATA22 and the heterodimer in vitro, consistent with RPA's role in protecting ssDNA and recruiting repair proteins. This study provides the first single-molecule elucidation of hMEIOB and hSPATA22 binding to ssDNA and verifies their relationship with the RPA complex.