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    Special Column of Aging
  • Taurine and Aging: Current Controversies and Potential Explanations
    JIN Tian-Ru
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1379-1392. https://doi.org/10.13865/j.cnki.cjbmb.2026.08.1083
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    A comprehensive study published in Science in 2023 reported that circulating taurine levels decline with aging across several mammalian species. Conversely, dietary taurine supplementation increased lifespan in worms and mice, as well as health span in monkeys. Although the authors have reported that dietary taurine supplementation can reduce cellular senescence, protect animals against telomerase deficiency, suppress mitochondrial dysfunction, decrease DNA damage, and attenuate cellular inflammation; detailed molecular mechanisms underlying those functions remain to be explored. Importantly, two recent studies, one published in Science and another one in Aging Cell, reported that low circulating taurine concentration is unlikely to be a good biomarker of aging. Following a general introduction on this semi-essential amino acid, the author has summarized main findings and controversies presented in these three investigations, briefly reviewed comments on these studies, and presented his perspectives for future studies from the angle of dietary intervention. A concern was raised regarding the tipping of the balance between reductionism and holism in experimental medicine, and two fundamental questions were discussed: (1) whether a universally applicable single driver of aging exists and (2) how to evaluate mechanisms underlying potential beneficial effects of taurine supplementation based on knowledge on bile acid homeostasis.
  • Aging and Entropy Increase: A Multi-level Entropy Increase Perspective on the Degradation Mechanisms of Biological Systems
    JIN Ning, TANG Jing-Jing, XIE Jun
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1393-1401. https://doi.org/10.13865/j.cnki.cjbmb.2026.04.1537
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    Aging is a complex and irreversible systemic degenerative process, the underlying mechanisms of which remain incompletely understood. This article proposes an integrative multilevel entropy increase framework from an interdisciplinary theoretical perspective, offering a systematic exposition of the fundamental drivers of aging. The framework elucidates the progressive accumulation of biological disorder and its consequences for functional decline across four hierarchical levels: biological macromolecules, epigenetic regulation, cellular homeostasis, and organismal homeostasis. It posits that aging originates in a foundational increase in disorder driven by thermodynamic entropy at the level of macromolecules and informational entropy within the epigenome. These primary sources of entropy are amplified through nonlinear dynamics, leading sequentially to increased entropy in cellular functions and systemic physiological regulation, culminating in the widespread deterioration of organismal function. Building on this model, the article further examines the mechanistic basis of aging intervention from an entropy increase perspective, emphasizing scientific strategies to counteract entropy increase at multiple levels,thereby slowing the progression of internal disorder and preserving the structural integrity and physiological stability of biological systems. This integrative framework not only provides a novel conceptual lens for understanding aging, but also establishes a logical foundation for developing anti-aging interventions focusing on enhancing negative entropy input, minimizing endogenous entropy production, and eliminating accumulated entropy.
  • The Role and Therapeutic Perspectives of Serpins in Alzheimer's Disease and Parkinson's Disease
    ZHOU Ming-Jin, GAO Guo-Quan, QI Wei-Wei
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1402-1410. https://doi.org/10.13865/j.cnki.cjbmb.2026.05.1088
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    Serine protease inhibitors (serpins) are a superfamily of proteins with highly diverse functions. Many members are expressed in the central nervous system and participate in the pathogenesis of neurodegenerative diseases through various mechanisms. Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders. This review systematically summarizes the latest research progress on serpin family members in AD and PD, including Serpin A3, Serpin A4, Serpin E1, Serpin F1, and Serpin G1. In AD, serpins act through multiple mechanisms: (1) In amyloid-beta (Aβ) metabolism, Serpin A3 and Serpin A4 promote Aβ aggregation and generation, Serpin E1 hinders Aβ clearance by inhibiting plasmin, while Serpin F1 negatively regulates Aβ formation; (2) In Tau protein phosphorylation, Serpin A3 and Serpin A4 induce tau hyperphosphorylation; (3) In glutamate homeostasis, Serpin F1 maintains homeostasis by stabilizing the glutamate transporter1 (GLT-1), whereas Serpin A4 disrupts it by degrading glutamine synthetase (GS); (4) Among other risk factors like neuroinflammation, Serpin A3 amplifies inflammatory responses, Serpin F1 inhibits neuroinflammation, and both Serpin A3 and Serpin E1 may be involved in the pathogenic mechanisms of ApoE4. In PD, Serpin E1 hinders the clearance of α-synuclein (α-Syn) by inhibiting plasmin, and Serpin G1 may promote α-Syn aggregation by affecting its phosphorylation. These findings reveal the complex roles of serpins in neurodegenerative diseases, where different members of the same family often exhibit double-edged sword effects. Serpins hold promise as novel biomarkers for disease diagnosis or as therapeutic targets. Precisely regulating their conformation, localization, and interaction networks may provide new avenues for developing safer and more effective therapies for AD and PD.
  • Metabolic Characteristics and Intervention Strategies in Hutchinson-Gilford Progeria Syndrome
    SUN Ying-Ying, PENG Meng-Fan, FU Xu-Dong
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1411-1423. https://doi.org/10.13865/j.cnki.cjbmb.2026.05.1089
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    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by clinical phenotypes resembling natural aging. Its pathogenesis is closely linked to mutations in the LMNA gene, which lead to abnormal processing of lamin A and the production of a cytotoxic protein known as progerin. Patients typically exhibit clinical features of accelerated aging from an early age, such as growth retardation, fat loss, joint stiffness, and severe cardiovascular lesions. This disease has long served as a model for studying the mechanisms of aging and holds significant importance in both basic and translational medicine, thus garnering considerable attention in rare disease research. Previous studies have primarily focused on nuclear envelope defects and genomic instability associated with the disease. However, recent research has revealed that HGPS also involves systemic metabolic dysregulation affecting key pathways such as energy metabolism, lipid homeostasis, and redox balance, with regulatory mechanisms encompassing dysregulation of the AMPK-mTOR signaling axis, mitochondrial dysfunction, and aberrant NAD+ consumption. These metabolic abnormalities do not exist in isolation but collectively drive the pathological progression of HGPS through interconnected regulatory networks. Based on this, the present review systematically outlines the key mechanisms and clinical manifestations of metabolic abnormalities in HGPS, with an emphasis on the therapeutic potential of targeting these metabolic nodes in HGPS models, aiming to provide a reference for a deeper understanding of HGPS pathogenesis and the development of metabolism-oriented therapeutic strategies.
  • The Mechanism of Ovarian Aging and the Potential Role of Natural Extracts
    LIANG Ya-Ping, HUANG Yun-Xuan, CHEN Jing
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1424-1437. https://doi.org/10.13865/j.cnki.cjbmb.2026.06.1094
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    The ovary plays a critical role in maintaining female reproductive function and endocrine homeostasis, and its aging is closely associated with the decline in female fertility. With declining global fertility rates and delayed childbearing, ovarian aging has become a major focus in reproductive medicine. Hallmarks of ovarian aging include diminished ovarian reserve, reduced oocyte quality, hormonal dysregulation, and dysfunction of the hypothalamic-pituitary-ovarian axis. Multiple mechanisms, including DNA damage accumulation, telomere shortening, oxidative stress, mitochondrial dysfunction, chronic low-grade inflammation, and cellular senescence, interact to promote follicular depletion and oocyte impairment. In addition, dysregulation of key signaling pathways, such as PI3K/AKT/mTOR, SIRT, AMPK, and NF-κB, further contributes to granulosa cell apoptosis, follicular atresia, and ovarian microenvironment imbalance, thereby accelerating ovarian functional decline. Recent studies have highlighted the therapeutic potential of natural extracts in delaying ovarian aging due to their low toxicity, multi-target properties, and antioxidant and anti-inflammatory activities. Natural bioactive compounds, including polyphenols, flavonoids, and saponins, can ameliorate ovarian aging by scavenging reactive oxygen species, improving mitochondrial function, suppressing inflammation, and modulating related signaling pathways. This article provides a systematic review of the primary mechanisms underlying ovarian aging and the potential role of natural extracts in delaying ovarian aging. It focuses on summarizing mechanisms such as the accumulation of DNA damage, mitochondrial dysfunction, oxidative stress, inflammation, and imbalances in related signaling pathways. It also elucidates the intervention potential of natural extracts from the perspective of multi-target and multi-pathway regulation, thereby providing new research insights and potential targets for future studies on targeted interventions for ovarian aging.
  • CRL4-DCAF13 Ubiquitin Ligase Complex Regulates the Senescence of Human Umbilical Vein Endothelial Cells Through the PI3K-AKT Pathway
    WANG Cai-Xia, ZHANG Long, ZHONG Jing-Ya, LIU Sheng-Bing, PAN Wei-Wei, WANG Ying-Nan
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1438-1449. https://doi.org/10.13865/j.cnki.cjbmb.2026.05.1488
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    This study investigates the effects of the CRL4 complex (cullin4 (CUL4)-RING E3 ubiquitin ligase complex) on the senescence and function of human umbilical vein endothelial cells (HUVECs). The results show that knocking down key components of the CRL4 complex (DDB1, ROC1, CUL4B) or DCAF13 (DDB1-CUL4 associated factors) significantly increases the number of senescent HUVECs by at least 4.5-fold and upregulates the expression of senescence-associated proteins such as PAI-1. Knockdown of DCAF13 also leads to increased expression of cell cycle-related proteins p21, p53, and cyclinB1, resulting in cell cycle arrest at the G1 phase, as well as inhibition of cell proliferation, migration, and tube formation capabilities. Mechanistically, DCAF13 deficiency reduces the activity of the PI3K-AKT signaling pathway, while overexpression of DCAF13 under PI3K inhibition alleviates cellular senescence. In summary, the newly identified CRL4-DCAF13-PI3K/AKT senescence pathway effectively influences the senescence process and cellular functions of HUVECs, suggesting its important role in vascular aging and related diseases, and providing a novel potential target for the prevention and treatment of cardiovascular diseases.
    • Reviews
  • The Role of Chromatin-remodeling Proteins in the Tumorigenesis and Progression of Pancreatic Cancer
    LU Xiao-Man, CHEN Mo
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1450-1457. https://doi.org/10.13865/j.cnki.cjbmb.2026.06.1025
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    Pancreatic ductal adenocarcinoma (PDAC) incidence is on a continuous rise worldwide, with approximately 450 000 new cases annually; it is projected to become the second leading cause of cancer-related deaths by 2030. Owing to the absence of early symptoms, most patients are diagnosed at a locally advanced or metastatic stage, and fewer than 20% are eligible for surgical resection. Conventional chemotherapy (e.g., gemcitabine plus albumin-bound paclitaxel) and immune-checkpoint inhibitors yield limited efficacy. Recent genomic sequencing of PDAC has revealed that driver mutations are highly enriched in a small set of genes—KRAS (>90%), TRP53 (~70%),CDKN2A, and SMAD4—yet targeting these alterations alone has failed to substantially improve prognosis. Epigenetic mechanisms, including modulation of chromatin architecture, histone modifications, DNA methylation, non-coding RNA expression, and post-transcriptional RNA processing, participate in virtually every step of tumorigenesis. In PDAC, widespread aberrations in chromatin-remodeling complexes, enhancer programs, and RNA-binding proteins have been identified as central to tumor maintenance and therapeutic resistance. Therefore, elucidating the oncogenic mechanisms of PDAC from an epigenetic perspective promises to deliver more precise clinical interventions.
  • The Molecular Mechanisms and Regulatory Characteristics of Ribosomal Stress Response
    XIONG Ye-Teng, LUO Fei, YANG Qin-Feng
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1458-1464. https://doi.org/10.13865/j.cnki.cjbmb.2025.12.1377
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    Beyond its essential role as the protein synthesis machinery, the ribosome also functions as a molecular sensor of cellular stress. The ribosome responds to detrimental environmental influences through three major translation surveillance pathways: the Ribotoxic Stress Response (RSR), Ribosome-associated Quality Control (RQC), and the Integrated Stress Response (ISR). RSR is primarily regulated by the kinase ZAKα, which senses ribosome stalling or collisions, leading to conformational changes and autophosphorylation. This activation triggers a downstream kinase cascade that modulates the expression of various stress-responsive genes, including pro-inflammatory cytokines and apoptosis-related proteins. RQC is a clearance mechanism targeting aberrant protein translation, initiated by recognition of a distinctive 40S-40S interface formed upon ribosome collisions. This pathway promotes degradation of defective mRNAs and aberrant polypeptides, thereby maintaining proteostasis and ensuring proper translation. ISR senses stress signals such as amino acid deprivation and ribosome stalling, phosphorylating translation initiation factors to suppress global translation while selectively upregulating specific stress response genes, thus exerting a dual regulatory effect. This review summarizes the molecular mechanisms and regulatory features of these ribosome-mediated stress responses, which may provide novel theoretical foundations and potential targets for disease prevention and therapy.
  • Therapeutic Strategies for Clearing Senescent Cells
    DAI Hao-Ran, QIAN Min-Xian
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1465-1472. https://doi.org/10.13865/j.cnki.cjbmb.2026.07.1165
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    Cellular senescence refers to the state in which cells permanently exit the cell cycle due to various internal and external stresses. It is believed to play a significant role in anti-tumor processes and the maintenance of homeostasis. However, the long-term accumulation of senescent cells is highly likely to lead to chronic inflammation and the onset of various age-related diseases. This article reviews the fundamental causes and characteristics of cellular senescence, as well as its impact on related clinical diseases. Building on an analysis of the advantages and disadvantages of senolytics for eliminating senescent cells, the paper focuses on research progress in senescence immunotherapy, the current challenges facing immunotherapy, and future research directions, thereby providing new perspectives and insights for the further development of effective anti-senescence therapies.
    • Research Paper
  • Chromatin O-GlcNAcylation-regulated Gene Expression Enhances the Metastatic Potential of Human Hepatocellular Carcinoma
    CHENG Hong-Ying, MA Qi-Le, HUANG Huang, ZHANG Na-Na, LIU Yu-Bo, ZHONG Xiao-Min
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1473-1484. https://doi.org/10.13865/j.cnki.cjbmb.2026.05.1028
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    Metastasis of hepatocellular carcinoma (HCC) is a major cause of poor patient prognosis and involves complex gene expression regulatory networks. O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is a dynamic post-translational modification enriched in the nucleus and has been implicated in multiple tumor-related biological processes; however, its genome-wide regulatory mechanisms underlying the metastatic phenotype of HCC remain unclear. In this study, we used human HCC cell lines with progressively increasing metastatic potential—MHCC97L, MHCC97H, and HCCLM3—as a model to systematically investigate the functional role and molecular mechanisms of chromatin O-GlcNAc glycosylation in HCC metastasis. Our results show that, with increasing metastatic potential, O-GlcNAc glycosylation levels of total cellular proteins and chromatin-associated proteins are markedly elevated in HCC cells. Pharmacological inhibition of O-GlcNAc glycosylation using small-molecule OGT inhibitors significantly reduces HCC cell migration and invasion. Furthermore, we employed a previously established metabolic labeling based chemoselective O-GlcNAc chromatin sequencing (COGC-seq) approach to map chromatin localization and gene regulatory functions of O-GlcNAc on a genome wide scale. As metastatic potential increases, O-GlcNAc-modified chromatin-binding signals are significantly enhanced and undergo extensive genome-wide redistribution. Integrated analysis with transcriptomic data reveals that O-GlcNAc-enriched genes related to metastasis and adhesion exhibit transcriptional activation. Motif analysis of O-GlcNAc chromatin-binding signals, together with functional assays, indicates that O-GlcNAc glycosylation enhances the binding of chromatin proteins such as GATA3 to target regulatory regions, thereby driving widespread transcriptional changes of downstream target genes. We further validated the regulatory effects of O-GlcNAc glycosylation on the transcription of ROBO1, CNTN6, FGF13, and ZC4H2, and confirmed that the expression of these target genes promotes the metastatic potential of HCC cells. In summary, this study reveals that O-GlcNAc glycosylation promotes HCC metastatic potential by reshaping the genome-wide localization of chromatin-binding proteins and regulating the expression of multiple metastasis- and invasion-associated genes.
  • Curcumin Alleviates Heat Stress-induced Testicular Damage and Spermatocyte Apoptosis in Mice by Regulating ATF3 Expression
    WANG Xue-Qin, XU Shu-Jian, HUANG Xin-Yang, HE Hai-Yang, LIU Yang, MA Bao-Hua, PENG Sha
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1485-1496. https://doi.org/10.13865/j.cnki.cjbmb.2026.04.1033
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    Heat stress (HS) can induce apoptosis in testicular cells of male animals, consequently disrupting spermatogenesis and leading to male reproductive dysfunction. Curcumin (CUR), a naturally occurring polyphenolic compound extracted from Curcuma longa, has potent efficacy against oxidative stress, inflammation, and immune-mediated injury. The purpose of this study was to evaluate the protective effect of curcumin on testicular germ cells in a murine model of heat stress. Employing ELISA, Western blot, and RT-qPCR, we showed that curcumin significantly reduced HS-induced testicular oxidative stress and apoptosis (P < 0.05). RNA-sequencing analyses further revealed that activating transcription factor 3 (ATF3) was significantly up-regulated after heat exposure, which was effectively suppressed by curcumin. ATF3 overexpression in GC-2 cells exacerbated heat-induced cellular injury, whereas knockdown of it significantly reduced apoptosis (P < 0.01). In conclusion, these findings uncover a novel mechanism by which curcumin mitigates heat-stress-induced damage to testicular germ cells through regulation of ATF3, offering theoretical insights and a possible therapeutic approach to prevent male reproductive failure caused by HS.
  • Investigating the Ameliorative Effects of Spermidine Combined with Resistance Exercise on Myocardial Oxidative Stress in Aging Model Rats via the Nrf2/ HO-1/GPX4 Pathway
    LI Hong-Jie, SUN Li-Li, HUANG Ni-Xi, SHI Lei, WANG Yu, LIAO Jiang-Rui, PENG Li-Na
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1497-1506. https://doi.org/10.13865/j.cnki.cjbmb.2026.06.1061
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    Myocardial oxidative stress imbalance during aging acts as a vital pathological factor triggering myocardial injury and cardiac dysfunction. The Nrf2/HO-1/GPX4 signaling pathway plays a core regulatory role in maintaining myocardial oxidative homeostasis and resisting oxidative damage. Both spermidine and resistance exercise exert favorable antioxidant effects and can alleviate tissue damage caused by excessive oxidative stress. Nevertheless, the regulatory efficacy and specific molecular mechanism of their combined intervention on myocardial oxidative stress in D-galactose-induced aging rats remain unclear. This study aims to explore the regulatory effect of 8-week spermidine combined with resistance exercise on myocardial oxidative stress in aging rats, and clarify its mechanism of improving oxidative stress via the Nrf2/HO-1/GPX4 signaling pathway. Eight-week-old healthy male SD rats were selected, and a rat aging model was established via 6-week D-galactose administration. Two rats were randomly chosen from the control group and model group respectively to verify modeling success. After confirming valid modeling, an 8-week intervention was implemented. Drug intervention was conducted by daily intraperitoneal injection of spermidine solution, and exercise intervention adopted gradient treadmill resistance training. All rats were divided into five groups: control group (Con), model group (Mod), resistance exercise group (Re), saline combined with resistance exercise group (Sal-Re), and spermidine combined with resistance exercise group (Spd-Re). Cardiac tissues were harvested 12 hours after the last training for subsequent detection. H&E staining and transmission electron microscope observation showed that the disordered arrangement of cardiomyocytes, myocardial fiber rupture and inflammatory cell infiltration were relieved in Re, Sal-Re and Spd-Re groups compared with Mod group, and Spd-Re group presented the most prominent improvement. ELISA detection revealed that GSH and HO-1 protein levels increased significantly while ROS content decreased markedly in Re and Sal-Re groups relative to Mod group (P<0.01). Spd-Re group obtained elevated levels of SOD, HO-1, GSH and GPX4 proteins and reduced MDA and ROS contents (P<0.05 or P<0.01). RT-qPCR results indicated that the mRNA expression of SOD, GPX4 and Nrf2 was upregulated obviously in Re and Sal-Re groups (P<0.05). Spd-Re group showed extremely higher mRNA levels of SOD, HO-1, GPX4 and Nrf2 (P<0.01), and its expression of HO-1, GPX4 and Nrf2 was statistically higher than that in Re and Sal-Re groups (P<0.05). Western blot assay demonstrated that the relative protein expression of Nrf2, SOD and GPX4 was enhanced in all intervention groups (P<0.05), with an extremely significant upward trend observed in Spd-Re group (P<0.01). Experimental results suggest that both spermidine and resistance exercise can upregulate the expression of proteins related to the Nrf2 signaling pathway. They effectively mitigate D-galactose-induced myocardial oxidative stress and delay myocardial aging in rats. The combined intervention achieves a better therapeutic effect than single resistance exercise. This finding provides theoretical reference for delaying age-related myocardial degenerative lesions.
  • Molecular Mechanism by Which the Bitter Taste Receptor TAS2R16 Recognizes β-D-glucoside Ligands
    WANG Chu-Lun, QIAO An-Na
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1507-1515. https://doi.org/10.13865/j.cnki.cjbmb.2026.05.1034
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    Bitter taste receptor 16 (TAS2R16) is a key member of the human bitter taste receptor family (TAS2Rs) and primarily mediates bitter taste signal transduction by recognizing compounds containing β-D-pyranoglucoside structures. TAS2R16 is predominantly expressed in the human oral cavity and has been implicated in the regulation of gingival inflammatory responses. In addition to its oral expression, TAS2R16 is also ectopically expressed in extra-oral tissues, where it is closely associated with multiple diseases. Although the structure of TAS2R16 in complex with its canonical ligand salicin has been resolved, the recognition patterns and molecular mechanisms by which TAS2R16 interacts with other β-D-pyranoglucoside ligands have not been systematically elucidated. In this study, based on the resolved TAS2R16-salicin complex structure, we selected a series of β-D-glucoside small molecules and performed an integrated analysis combining molecular docking and intracellular Ca2+mobilization assays. We systematically characterized the binding poses and functional effects of different ligands within the TAS2R16 binding pocket. Our results reveal that TAS2R16 adopts a conserved glycosyl recognition pattern to achieve common binding to β-D-glucoside ligands, while variations in aromatic ring substituents further modulate the fine-tuned ligand conformations within the pocket and receptor activation efficacy. Site-directed mutagenesis of key interacting residues markedly attenuated TAS2R16-mediated Ca2+responses without affecting receptor cell-surface expression. Collectively, this study elucidates the structural and functional basis of β-D-glucoside recognition by TAS2R16, providing new experimental insights into ligand selectivity and the potential non-gustatory functions of bitter taste receptors.
  • Regulatory Effects of Asprosin on the Hypothalamic Kisspeptin-GnRH Signaling Axis and Mechanisms of Exercise Intervention in Obese Male Mice
    ZHANG Chao, LV Hong-Yan, YAO Ting-Ting, LIU Zi-Ao, LIU Ming, YI Xue-Jie
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1516-1524. https://doi.org/10.13865/j.cnki.cjbmb.2026.05.1020
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    Obesity-induced reproductive dysfunction has emerged as a critical health challenge. While exercise is known to effectively mitigate this condition, the underlying molecular mechanisms remain poorly understood. This study focuses on a novel adipokine, Asprosin (ASP), to investigate its regulatory role on the hypothalamic Kisspeptin-GPR54-GnRH signaling axis and to determine whether exercise improves reproductive dysfunction by modulating ASP expression. Fbn1 heterozygous knockout (Fbn1+/-) mice and wild-type (WT) littermates were utilized, with exogenous ASP protein or saline administered to verify the direct regulatory effects of ASP. Additionally, a high-fat diet-induced obesity model was established, with mice randomly assigned to an obesity control (OC) group and an obesity exercise (OE) group (10 weeks of treadmill training). At the end of the experiment, body weight and abdominal fat parameters were measured. Immunofluorescence (IF) was used to locate the spatial relationship between ASP and Kisspeptin neurons in the hypothalamic arcuate nucleus (ARC). mRNA and protein levels of ASP, Kisspeptin, GPR54, and GnRH were detected via RT-qPCR and Western blotting. IF results showed significant colocalization of ASP and Kisspeptin in the ARC, providing a structural basis for their interaction. Compared with the WT group, the expression of Kisspeptin, GPR54, and GnRH in the Fbn1+/-group was significantly reduced (P<0.01), whereas exogenous ASP injection significantly reversed this downregulation (P<0.01). In the obesity model, hypothalamic ASP levels and Kisspeptin axis signaling were significantly suppressed in the OC group (P<0.01). Notably, 10 weeks of aerobic exercise significantly increased hypothalamic ASP levels in the OE group compared to the OC group (P<0.05). In conclusion, ASP acts as a key positive regulator of the hypothalamic Kisspeptin-GPR54-GnRH signaling axis. Central ASP deficiency is a vital molecular mechanism underlying obesity-related HPG axis impairment. Aerobic exercise activates the Kisspeptin pathway by enhancing hypothalamic ASP expression, thereby improving reproductive endocrine function. This study provides experimental evidence for understanding the neuroendocrine mechanisms of exercise-induced reproductive health and offers scientific insights for developing exercise intervention strategies.
  • The Regulatory Effect of IP3R/GRP75/VDAC1-mediated Mitochondrial Ca2+ Overload on Paraptosis Induced by DpdtC in BV2 Microglial Cells
    ZHOU Wei, WEI Hui-Ping, LI Yong-Li, LI Chang-Zheng
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1525-1534. https://doi.org/10.13865/j.cnki.cjbmb.2026.06.1045
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    Microglia BV2 is the main immune effector cell in the brain, with endogenous immune defense function. Many drugs have excellent biological activity, but there is limited research on their effects on glial cells. This study aimed to investigate the effects and molecular mechanisms of dipyridylketone dithiocarbamate (DpdtC) on microglia. MTT results showed that DpdtC significantly inhibited the growth of BV2 cells via ROS-mediated mechanisms and induced G1 phase cell cycle arrest. AO-EB staining and flow cytometry analysis suggested the occurrence of apoptosis. Western blot analysis revealed that at high concentrations, the expression level of Bcl-2 decreased, while cleaved caspase-3 significantly increased, indicating apoptosis involvement, albeit with a weak contribution to growth inhibition. ER staining revealed that DpdtC could also induce cytoplasmic vesiculation, accompanied by downregulation of alix, indicating the occurrence of paraptosis. Additionally, a decrease in MDM2-mediated p53 expression was observed. DpdtC treatment also led to increased calcium levels in the cytoplasm and mitochondria, and upregulation of IP3R/GRP75/VDAC1 expression. Combined treatment with IP3R inhibitor (2-APB) and DpdtC downregulated IP3R/GRP75/VDAC1 expression, but enhanced alix expression, suggesting that this pathway plays a regulatory role in paraptosis. In addition, DpdtC could also inactivate the PI3K/AKT/mTOR pathway. In summary, this study confirms that the growth inhibition of DpdtC on microglial BV2 cells involved apoptosis, paraptosis, IP3R/GRP75/VDAC1 mediated mitochondrial calcium overload, and inactivation of the PI3K/AKT/mTOR pathway; The association between paraptosis and mitochondrial calcium overload mediated by IP3R/GRP75/VDAC1 has been reported for the first time.
  • Construction of a Prognostic Risk Model for Colorectal Cancer Based on DNA Damage Repair-related Genes and Functional Studies of ATP2A1
    LIU Qi-Xiang, WANG Jia-Dong
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1535-1547. https://doi.org/10.13865/j.cnki.cjbmb.2026.05.1011
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    To construct a prognostic risk model for colorectal cancer (CRC) based on DNA damage repair (DDR)-related genes and to explore the biological significance of ATPase sarcoplasmic/endoplasmic reticulum Ca2+transporting 1 (ATP2A1), transcriptomic and clinical data of CRC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The least absolute shrinkage and selection operator-Cox regression (LASSO-Cox) analysis was performed to identify prognostic DDR-related genes and establish a risk score model. The predictive performance of the model was evaluated using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves. Tumor immune cell infiltration was assessed using CIBERSORT, single-sample gene set enrichment analysis (ssGSEA), and XCELL algorithms. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were conducted to investigate the potential functional mechanisms of ATP2A1. The expression of ATP2A1 in CRC cell lines was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). A prognostic model comprising 9 DDR-related genes (CPT2, SIX4, CXXC5, NAT1, MC1R, LRP2, ATP2A1, CYP19A1, and NKX2-5) was successfully constructed, which stratified patients into high- and low-risk groups with significantly different overall survival outcomes (P < 0.0001). ATP2A1 was identified as a core risk gene and was significantly overexpressed in CRC tissues, with high expression associated with a poor prognosis. Immune infiltration analyses revealed that ATP2A1 expression was closely correlated with multiple immune cell subsets. Functional enrichment analyses suggested that ATP2A1 is mainly involved in calcium homeostasis, endoplasmic reticulum stress, and mismatch repair pathways. In vitro experiments further confirmed that ATP2A1 expression was significantly upregulated in CRC cell lines. The nine-gene signature represents a potential independent prognostic indicator for CRC. Within the context of a DDR-related molecular network, this study further validates the prognostic relevance of ATP2A1 and highlights its potential as a therapeutic target and biomarker in CRC.
  • Design of a Chimera RING-βsyn Based on the TRIM-Away for Targeted Degradation of α-Synuclein
    WANG Zhen, GAN Shi-Yu, REN Xiao-Xi, ZHOU Tai, KONG Fang-Qing-Qing, ZHANG Jian-Liang
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1548-1555. https://doi.org/10.13865/j.cnki.cjbmb.2026.06.1036
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    Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, pathologically characterized by the aberrant aggregation of α-synuclein (α-syn) and the formation of Lewy bodies. In recent years, targeted protein degradation has emerged as a promising therapeutic strategy for PD. Among these approaches, the TRIM-Away technology harnesses the specific interaction between the endogenous E3 ubiquitin ligase TRIM21 and target-specific antibodies to enable rapid and selective degradation of target proteins. Based on this principle, we engineered a novel chimeric molecule, RING-βsyn, designed to efficiently degrade α-syn. Using human embryonic kidney 293T (HEK293T) cells and neuroblastoma SH-SY5Y cells, we demonstrated that RING-βsyn effectively eliminates intracellular α-syn in a concentration-dependent manner. Furthermore, RING-βsyn treatment restored cell viability and alleviated α-syn-induced cytotoxicity. Collectively, this study establishes an innovative therapeutic strategy that efficiently clears pathological α-syn and halts PD-associated pathological progression, thereby circumventing the limitations of the canonical TRIM-Away system, which requires sustained supplementation of TRIM21 protein and the introduction of high-molecular-weight antibodies.
    • Education and Teaching
  • Practice and Thought onthe Experimental Design-based Assessment of Medical Biochemistry and Molecular Biology
    LIU Yang-Wu-Yue, ZHAO Yuan-Yin, LI Tao, XU Zhi-Zhen, HE Feng-Tian, HUANG Gang, CHEN Shan, DAI Shuang-Shuang
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1556-1566. https://doi.org/10.13865/j.cnki.cjbmb.2026.02.1469
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    Medical biochemistry and molecular biology are the cornerstones of modern life sciences, and the effectiveness of their teaching directly affects the quality of talent cultivation in life sciences and medicine. The traditional closed-book examination method, which mainly consists of multiple-choice questions, fill-in-the-blank questions, and short-answer questions, focuses more on the memorization and recitation of discrete and factual knowledge points. This assessment model plays an indispensable role in ensuring the basic quality of teaching and the objectivity of evaluation. However, with the innovation of educational concepts and the dramatic change in the country's demand for innovative talents, its inherent limitations have become increasingly prominent, creating a gap with the practical, logical, and innovative nature of the discipline, and gradually making it difficult to fully meet the diverse needs of innovative talent cultivation. This article focuses on the innovative assessment and evaluation model of "assessment based on experimental design" as a supplement to the traditional assessment model, and initially explores its question form, implementation details, and feedback from teachers and students. It summarizes the inherent advantages, potential challenges, and improvement methods in this process, providing a new idea for the assessment reform of basic biochemistry and molecular biology in the context of "new medicine".
    • Cover Image Introduction
  • Chromatin O-GlcNAcylation-regulated Gene Expression Enhances the Metastatic Potential of Human Hepatocellular Carcinoma(see page 1473)
    Cover picture designer ZHONG Xiao-Min
    Chinese Journal of Biochemistry and Molecular Biology. 2026, 42(8): 1567-1567.
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