Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024186
Pyruvate dehydrogenase kinase 1 (PDK1) is a new therapeutic target that is dysregulated in multiple tumors. This study aims to explore the potential role and regulatory mechanism of PDK1 in epithelial ovarian cancer (EOC). We detect PDK1 expression in EOC tissues and cells using qRT-PCR and western blot analysis, and the effects of PDK1 on EOC cell malignant behaviors are explored. RNA sequencing analyses are performed to explore the differentially expressed genes in PDK1-silenced EOC cells. Furthermore, tumor-bearing mouse models are established to assess the impacts of PDK1 and BGN on EOC tumor growth and metastasis in vivo. The results show that PDK1 is upregulated in EOC tissues and cell lines. Biglycan (BGN) is downregulated in PDK1-silenced EOC cells, and its expression is positively correlated with PDK1 levels in EOC tissues. PDK1 depletion inhibits EOC cell proliferation, migration and invasion. Mechanistically, PDK1 and BGN are colocalized in the cytoplasm of EOC cells and interact with each other. PDK1 positively regulates BGN expression by enhancing BGN mRNA stability. BGN overexpression partially reverses the anti-tumor effects of PDK1 depletion on EOC cell malignant behaviors. PDK1 has also been revealed to upregulate BGN to activate the NF-κB oncogenic pathway in EOC cells. Additionally, PDK1 accelerates tumor growth and metastasis by modulating BGN expression. In conclusion, PDK1 functions as an oncogene, facilitating EOC progression by upregulating BGN and activating the NF-κB pathway. These findings may provide valuable biomarkers for the diagnosis and treatment of EOC.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025122
Long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of hepatocellular carcinoma (HCC), but the functions and molecular mechanisms of large lncRNAs remain unclear. In this study, HCC data from The Cancer Genome Atlas (TCGA) and 116 HCC cases from our clinical center are used to identify a novel lncRNA, RP11-439C15.4, which is significantly downregulated in HCC. This downregulation is associated with poor prognosis in HCC patients. A series of in vitro and in vivo experiments demonstrate that RP11-439C15.4 significantly inhibits the proliferation, invasion, migration and sorafenib resistance of HCC cells. Further mechanistic investigations reveal that RP11-439C15.4 interacts with DExH-Box Helicase 9 (DHX9) to increase its ubiquitination and accelerate the degradation of DHX9, ultimately suppressing HCC progression. Modulation of DHX9 significantly reverses the effects of RP11-439C15.4 in HCC. In conclusion, this study identifies RP11-439C15.4 as a tumor suppressor and elucidates the regulatory mechanism of the RP11-439C15.4/DHX9 axis in HCC, providing valuable insights into the mechanisms of HCC progression and potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025101
Abnormal proliferation and migration of endothelial cells are key contributors to tumor angiogenesis. Recent studies have shown that the crucial role of E3 ubiquitin ligase neuronal precursor cell expression developmentally downregulated 4-like (NEDD4L) in tumorigenesis. However, the precise mechanisms by which NEDD4L functions in endothelial cells remain unclear. In this study, we investigate the mechanisms by which NEDD4L influences the function of human umbilical vein endothelial cells (HUVECs) and its effect on tumor angiogenesis. Our results show that NEDD4L overexpression in HUVECs suppresses both cell proliferation and migration. Additionally, we find that the autophagic activity in NEDD4L-overexpressing cells is increased. Proteomic profiling and ubiquitination assays reveal that NEDD4L interacts with eEF1A1, promoting K48-linked ubiquitination-mediated degradation of eEF1A1. This post-translational modification is a key step in the NEDD4L-mediated regulation of autophagy and cellular function. Moreover, we find that loss of endothelial NEDD4L significantly enhances tumor growth and promotes angiogenesis in vivo. Overall, NEDD4L plays a crucial role in inhibiting tumor angiogenesis by regulating eEF1A1 ubiquitination and degradation, providing new insights into the NEDD4L-eEF1A1 axis and its potential as a therapeutic target.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025220
Emerging studies have revealed that disruptions in circadian crosstalk between the gut microbiota and the host play an essential role in the pathogenesis of metabolic disorders. Under physiological conditions, host circadian clocks regulate microbial diurnal oscillations through rhythmic behaviors, including feeding patterns and sleep-wake cycles. This temporal regulation manifests as robust 24-hour oscillations in microbial community composition, spatial organization, and metabolic activity. These rhythmic microbial signals and their metabolic outputs are subsequently translated into host immune modulation, establishing a bidirectional temporal dialogue between the host and microbiota. Modern lifestyle disruptions, including erratic eating patterns and shift work, desynchronize this temporal dialogue, leading to the loss of microbial rhythms, impaired intestinal barrier function, maladaptive immune responses, chronic inflammation, and systemic metabolic dysregulation. This review delineates the mechanisms through which host-microbiota circadian crosstalk governs immunometabolic homeostasis, provides a mechanistic framework for understanding immunometabolic diseases, and highlights therapeutic strategies that target microbial rhythms to reset host immunity and metabolism.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024009
Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024087
The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261624
The bHLH transcription factor family in Forsythia suspensa was systematically identified and characterized using genomic data, yielding 170 members with complete HLH conserved domains distributed across 14 chromosomes. Protein lengths ranged from 67 to 885 amino acids, with relative molecular masses of 7,910.58 to 98,854.78 and theoretical isoelectric points of 4.71 to 10.44. Phylogenetic analysis classified these factors into 13 subfamilies, with subfamily III being the largest. Cis-acting element analysis revealed multiple light-, hormone-, and stress-responsive elements. Exogenous methyl jasmonate (MeJA) treatment of F. suspensa leaves followed by qRT-PCR within 48 h and correlation with phillygenin content identified FsbHLH26 and FsbHLH139 as likely key regulators of phillygenin biosynthesis and accumulation. These findings provide a foundation for elucidating the molecular mechanisms underlying phillygenin biosynthesis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21260
BACKGROUND: As a group of ubiquitous exogenous compounds in the environment, endocrine disrupting chemicals can interfere with endocrine system function and contribute to various diseases. In recent years, the correlation between exposure to endocrine disrupting chemicals and type 1 diabetes risk has become a research hotspot, but the exact underlying mechanisms remain unclear. OBJECTIVE: To review the research progress on the association between endocrine disrupting chemicals and type 1 diabetes in terms of epidemiological studies, animal experiments, and related mechanism studies. METHODS: The literature retrieval was conducted on CNKI and PubMed databases from January 2000 to January 2025 with the keywords of “endocrine disrupting chemicals; EDCs; type 1 diabetes; T1DM” in Chinese and English, respectively. A total of 55 articles were selected for the review. RESULTS AND CONCLUSION: Typical endocrine disrupting chemicals such as bisphenol A, pesticides and heavy metals can promote the development of type 1 diabetes through various pathways, including inducing immune dysregulation, activating oxidative stress, and epigenetic regulation. However, existing studies are limited by issues such as non-unified exposure assessment methods, an unclear dose-response relationship, and population heterogeneity. Future research should focus on identifying critical exposure windows and integrating multi-omics approaches to provide new strategies for the prevention of type 1 diabetes.
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.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21336
BACKGROUND: High-altitude hypoxia has been reported to damage the male reproductive system, but whether stem cells can protect against male reproductive damage caused by high-altitude hypoxia has not been reported. OBJECTIVE: To investigate the preventive effect of human umbilical cord mesenchymal stem cell transplantation on reproductive damage in hypoxia-exposed male mice. METHODS: Human umbilical cord mesenchymal stem cells were isolated and cultured, and three-lineage differentiation and flow cytometry identification were performed. Twenty-one C57BL/6 male mice were randomly divided into control, hypoxia, and stem cell groups (n=7). The hypoxia and stem cell groups were exposed to a chronic intermittent hypoxia model simulating an altitude of 5,000 m (11.1% oxygen). In the stem cell group, 1×10^6 human umbilical cord mesenchymal stem cells were injected via the tail vein once a week for 6 weeks, while the other groups received PBS. Body mass, food intake, and water intake were monitored. After hypoxia exposure, testicular tissue was analyzed for morphology, ultrastructure, reactive oxygen species levels, and mitochondrial membrane potential; epididymal tissue was analyzed by hematoxylin-eosin staining and sperm motility; and the homing ability of stem cells was observed by DiL fluorescence tracing. RESULTS AND CONCLUSION: Human umbilical cord mesenchymal stem cell transplantation significantly improved water and food intake in hypoxic mice but had no significant effect on body mass. Morphological analysis showed that hypoxia caused edema of the testis and epididymis and shedding of spermatogenic cells, while stem cell transplantation alleviated these structural damages and reversed mitochondrial swelling and atrophy in germ cells. Additionally, stem cell transplantation significantly inhibited hypoxia-induced increase in reactive oxygen species, restored mitochondrial membrane potential, and improved sperm motility. Tracing experiments showed that after entering the mice, stem cells mainly accumulated in lung tissue, with low homing to the testis. In conclusion, human umbilical cord mesenchymal stem cell transplantation can protect the structure and function of germ cell mitochondria, reduce hypoxia-induced testicular and epididymal edema, and thereby restore spermatogenesis and sperm motility.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026117
SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.