BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE生物化学与生物物理学报-疾病的分子基础
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE(英文缩写 BBA-MOL BASIS DIS),ISSN 0925-4439,eISSN 1879-260X,中文译名:生物化学与生物物理学报-疾病的分子基础 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.633 | Q1 |
| 2022 | 6.200 | Q1 |
| 2023 | 4.200 | Q1 |
| 2024 | 4.200 | Q1 |
| 2025 | 5.000 | Q1 |
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 最新收录文献
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1. Interplay between ferroptosis and cuproptosis in chronic kidney disease: Mechanisms and regulatory crosstalk.
1. 铁死亡与铜死亡在慢性肾脏病中的相互作用：机制与调控串扰PMID:日期:2026-10-02[中文摘要] 慢性肾脏病（CKD）以肾脏结构和功能的进行性、不可逆性恶化为特征，构成重大的全球公共卫生负担。铁死亡和铜死亡是近年来发现的两种金属依赖性调节性细胞死亡形式，均与CKD的发病机制相关。重要的是，这两条通路并非独立运作，而是通过涉及氧化还原失衡、线粒体功能障碍和金属稳态紊乱的共同机制发生汇聚。CKD相关微环境包括代谢功能障碍、尿毒症毒素蓄积、慢性缺氧、炎症和细胞外基质重塑，可增强肾细胞对上述两种过程的易感性。共同的调控节点，尤其是GSH-GPX4轴、p53和Nrf2，整合了抗氧化防御、金属代谢和线粒体功能，从而将这两条通路联系起来。在本综述中，我们系统总结了铁死亡和铜死亡在CKD中的分子机制，讨论了CKD微环境如何重塑细胞对铁死亡和铜死亡的易感性，并重点阐述了GSH-GPX4轴、p53和Nrf2作为潜在分子汇聚枢纽的调控作用。我们还探讨了尚未解决的关键问题，包括两者相互作用的直接证据有限、对细胞类型特异性机制的理解不完整、缺乏可靠的生物标志物以及临床转化面临的挑战。总体而言，现有证据支持以下观点：铁死亡和铜死亡是金属-氧化还原-线粒体网络中依赖情境且相互关联的组成部分，对其精准调控可能为CKD提供基于机制、由生物标志物指导的新型干预策略。
[英文摘要] Chronic kidney disease (CKD) is characterized by progressive and irreversible deterioration of renal structure and function, posing a substantial global public health burden. Ferroptosis and cuproptosis are two recently identified forms of metal-dependent regulated cell death implicated in CKD pathogenesis. Importantly, these pathways do not operate independently; rather, they converge through shared mechanisms involving redox imbalance, mitochondrial dysfunction, and disrupted metal homeostasis. The CKD-associated microenvironment, encompassing metabolic dysfunction, uremic toxin accumulation, chronic hypoxia, inflammation, and extracellular matrix remodeling, enhances renal cell susceptibility to both processes. Common regulatory nodes, particularly the GSH-GPX4 axis, p53, and Nrf2, integrate antioxidant defense, metal metabolism, and mitochondrial function, thereby linking these two pathways. In this review, we systematically summarize the molecular mechanisms of ferroptosis and cuproptosis in CKD, discuss how the CKD microenvironment reshapes cellular susceptibility to ferroptosis and cuproptosis, and highlight the regulatory roles of the GSH-GPX4 axis, p53, and Nrf2 as potential molecular convergence hubs. We also address key unresolved issues, including limited direct evidence for their interaction, incomplete understanding of cell type-specific mechanisms, the lack of reliable biomarkers, and challenges in clinical translation. Collectively, current evidence supports the concept that ferroptosis and cuproptosis are context-dependent and interconnected components of a metal-redox-mitochondrial network, and that its precise modulation may offer novel strategies for mechanism-based, biomarker-guided intervention in CKD.
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2. USP36-mediated stabilization of NAT10 promotes osteosarcoma progression via ac4C-dependent KIF23 mRNA stabilization.
2. USP36介导的NAT10稳定化通过ac4C依赖的KIF23 mRNA稳定化促进骨肉瘤进展PMID:日期:2026-10-02Osteosarcoma is an aggressive bone malignancy with a propensity for pulmonary metastasis, yet the molecular mechanisms linking protein homeostasis to epitranscriptomic regulation remain incompletely understood. Here, integrated transcriptomic, survival, protein-interaction, and CRISPR dependency analyses identified the deubiquitinase USP36 as a driver of osteosarcoma progression. USP36 was elevated in osteosarcoma datasets, and higher expression was associated with poorer survival in univariable analysis. Functional studies showed that USP36 depletion suppressed osteosarcoma-cell proliferation and invasion, whereas USP36 overexpression enhanced these phenotypes. Re-expression of wild-type USP36, but not the catalytically inactive C131A mutant, restored clonogenic growth and invasive capacity in USP36-deficient cells, indicating that its tumor-promoting effects depend on catalytic activity. Mechanistically, USP36 interacted with NAT10, prolonged NAT10 protein stability, and reduced K48-linked NAT10 polyubiquitination in cells. USP36 depletion decreased ac4C enrichment on KIF23 mRNA, accelerated KIF23 transcript decay, reduced KIF23 and β-catenin abundance, and impaired Wnt/β-catenin transcriptional activity. Importantly, wild-type NAT10, but not the catalytically inactive NAT10-G641E mutant, restored KIF23 ac4C enrichment, KIF23 expression, Wnt reporter activity, and clonogenic growth after USP36 depletion. TCF3 bound the USP36 promoter and positively regulated endogenous USP36 expression, whereas Wnt inhibition reduced USP36 transcription, supporting a reinforcing TCF3-USP36-NAT10-KIF23-Wnt regulatory relationship. In vivo, USP36 depletion reduced orthotopic tumor burden and experimental pulmonary metastatic colonization. Collectively, these findings identify USP36 as an upstream regulator of NAT10 stability and establish a mechanistic link between ubiquitin-dependent protein turnover and ac4C-mediated KIF23 mRNA stabilization in osteosarcoma. The USP36-NAT10-KIF23 axis may therefore represent a molecular vulnerability warranting further biochemical and clinical investigation.
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3. Integrated transcriptomic and deep learning analyses define acRG signature for prognosis and therapeutic options in osteosarcoma.
3. 整合转录组学和深度学习分析确定了用于骨肉瘤预后和治疗选择的acRG特征PMID:日期:2026-10-02Osteosarcoma is a highly malignant bone tumor characterized by significant clinical heterogeneity and poor prognostic outcomes. In this study, we integrated single-cell RNA sequencing data to characterize the landscape of genes related to N-acetylcytidine (ac4C) modification. We calculated an acRG activity score and found that activity was predominantly enriched in osteoblastic cells. Using a machine learning framework, we constructed a six-gene prognostic signature termed acRGBS. This signature served as a robust and independent predictor of overall survival across multiple independent cohorts. Further analysis revealed that high acRGBS scores were associated with an immunosuppressive tumor microenvironment and increased immune evasion potential. Among the hub genes identified, S100A13 was highlighted as a potential driver of tumor progression. Functional experiments demonstrated that S100A13 knockdown significantly inhibited cell proliferation and reduced xenograft tumor growth in vivo. Mechanistically, S100A13 physically interacts with the mitochondrial calcium uniporter (MCU) to maintain mitochondrial calcium homeostasis. Silencing S100A13 led to mitochondrial calcium overload, which exacerbated oxidative stress and induced cell apoptosis. Finally, we showed that S100A13 knockdown significantly enhanced the anti-tumor efficacy of cisplatin treatment. These findings suggest that S100A13 is a promising therapeutic target and a valuable biomarker for risk stratification in patients with osteosarcoma.
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4. Crosstalk between visceral adipose tissue secretome and tumoral microenvironment in obesity-induced colorectal cancer.
4. 肥胖诱导的结直肠癌中内脏脂肪组织分泌组与肿瘤微环境之间的串扰PMID:日期:2026-10-01Currently, colorectal cancer (CRC) remains a major global health challenge, with a rising incidence linked to a sedentary lifestyle and metabolic diseases, the main player being obesity (OB). Visceral adipose tissue (VAT) emerged as a key mediator of this association, functioning as a highly active endocrine-immune organ, rather than a mere energy reservoir. In OB, VAT undergoes pathological remodeling, including adipocyte hypertrophy and hypoxia, leading to a state of chronic low-grade inflammation. This review explores the mechanisms by which the dysfunctional VAT secretome orchestrates remodeling of the colorectal tumor microenvironment (TME). The dysfunctional obese VAT is characterized by an imbalance in adipokine secretion (e.g., decreased adiponectin, increased leptin, and resistin), pro-inflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β), and chemokines, which drive an inflammatory state. We describe the "gut-VAT-tumor axis", illustrating how intestinal dysbiosis and increased permeability, especially for lipopolysaccharides (LPS), toxins, or short-chain fatty acids (SCFAs), trigger metabolic endotoxemia, further activating inflammatory pathways within VAT. These systemic changes remodel the colorectal TME by stimulating pathological angiogenesis, inducing epithelial-mesenchymal transition (EMT), and creating a permissive niche for immune evasion through the recruitment of immune suppressor cells. Furthermore, the role of exosomal microRNAs is highlighted as mediators of cellular crosstalk that enhance tumor aggressiveness. Also, this review analyzes emergent biomarkers identified through multi-omics, such as the systemic inflammation response index (SIRI) and specific microbiomic signatures, alongside the potential of liquid biopsy for real-time monitoring. In conclusion, the dysfunctional VAT secretome is the central architect in remodeling the CRC TME, thereby promoting the initiation, progression, and aggressiveness of this malignancy. This aspect is making the VAT secretome a vital target for future diagnostic and targeted therapeutic strategies for obese patients with CRC.
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5. Loss of PIMREG impairs double-strand break signaling and repair.
5. PIMREG的缺失会损害双链断裂信号传导和修复PMID:日期:2026-09-29Glioblastoma (GBM) is the most common primary brain tumor in adults. It is an aggressive type of tumor with an average overall survival of 12-15 months post-diagnosis. Standard treatment involves surgical resection, followed by radiotherapy and chemotherapy with temozolomide (TMZ). However, resistance to treatment is frequently observed. PIMREG is a marker of proliferation highly expressed across different tumor types, with particularly elevated levels in GBM. Our previous study revealed that PIMREG silencing sensitizes GBM cells to TMZ treatment and affects ATM activation, a key apical kinase involved in DNA damage signaling. Given the emerging significance of PIMREG in the DNA damage response, we sought to explore PIMREG's role in DNA damage repair and signaling in GBM cells exposed to genotoxic agents. Here we assessed the functionally enriched pathways associated with high PIMREG expression in GBM patient samples, analyzed the interactome of PIMREG upon treatment of GBM cells with TMZ and evaluated the impact of PIMREG loss on DNA damage signaling, DNA break formation and the repair of double-strand breaks. Our findings reveal that PIMREG functions as a direct substrate for ATM/ATR kinases, interacts with key DNA repair proteins upon TMZ treatment and actively facilitates the cellular response to chemotherapy- and radiotherapy-induced DNA damage. Taken together, PIMREG may function in the DNA damage response, particularly in the signaling and repair of double strand breaks via homologous recombination in GBM cells. In all, our data suggested high PIMREG expression may affect resistance of GBM cells to treatment.
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6. Dichloroacetate mitigates experimental abdominal aortic aneurysm via suppression of CXCL5-mediated neutrophil chemotaxis.
6. 二氯乙酸通过抑制CXCL5介导的中性粒细胞趋化作用减轻实验性腹主动脉瘤PMID:日期:2026-09-29Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with high rupture-associated mortality. Current management relies on surgical or endovascular repair, with no effective pharmacological therapy. Inflammation and immune cell infiltration are central to AAA pathogenesis, but the molecular mechanisms remain incompletely defined. Human AAA tissues and murine AAA models (CaCl and porcine pancreatic elastase) were analyzed for chemokine expression and immune cell infiltration. The role of CXCL5 was investigated using immunohistochemistry, RNA-seq, and flow cytometry. The pharmacological effects of dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, were assessed in vitro in smooth muscle cells and in vivo in AAA models. CXCL5 was markedly enriched in human AAA lesions and associated with neutrophil infiltration. In murine AAA, neutrophil accumulation was evident and correlated with CXCL5 expression. DCA treatment suppressed ROS generation and NF-κB activation in smooth muscle cells, thereby reducing CXCL5 expression. Functionally, DCA significantly attenuated AAA formation in both CaCl- and elastase-induced models. Mechanistically, DCA mitigated AAA progression by inhibiting CXCL5-mediated neutrophil chemotaxis. CXCL5-driven neutrophil recruitment is a key mechanism in AAA pathogenesis. DCA suppresses CXCL5 expression through inhibition of oxidative stress and NF-κB signaling, conferring protection against experimental AAA. These findings highlight CXCL5 as a potential therapeutic target and establish DCA as a promising candidate drug for AAA treatment.
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7. Lipid-autophagy crosstalk in glioblastoma: A context-dependent stress-adaptation interface under temozolomide pressure.
7. 胶质母细胞瘤中的脂质-自噬交叉对话：替莫唑胺压力下依赖于情境的应激适应界面PMID:日期:2026-09-28Glioblastoma (GB) is characterized by aggressive progression and frequent recurrence despite temozolomide (TMZ)-based therapy. Although resistance is commonly linked to DNA repair mechanisms, these pathways do not fully explain tumor persistence under therapeutic stress. Accumulating evidence suggests that metabolic reprogramming, particularly crosstalk between lipid metabolism and autophagy, may contribute to GB adaptation under TMZ-induced stress. We discuss how this lipid-autophagy interface may enable tumor cells to reconfigure energy production, maintain redox balance, and remodel membranes in response to therapy. Although the available evidence remains predominantly preclinical, convergent findings from lipidomic analyses and functional perturbation studies support lipid-autophagy crosstalk as an emerging contributor to TMZ resistance. This review presents this interaction as a testable conceptual framework for understanding metabolic adaptation to TMZ and discusses its potential therapeutic relevance.
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8. Claudin-5 regulates mitochondrial bioenergetics and protects the heart against myocardial infarction.
8. Claudin-5调节线粒体生物能量学并保护心脏免受心肌梗死PMID:日期:2026-09-26Claudin-5 (Cldn5) is traditionally recognized as a key component of endothelial tight junctions, however, its potential intracellular function within cardiomyocytes remains largely unexplored. This study aims to explore the molecular mechanisms underlying the cardioprotective role of Cldn5 on myocardial infarction (MI). We identified mitochondrial localization of Cldn5 in cardiomyocytes in human heart tissues and cardiomyocytes by western blot, histochemistry, immunofluorescence and immuno‑gold electron microscopy. Knockdown of Cldn5 in HL-1 cells via siRNA decreased mitochondrial number, increased cellular ADP/ATP ratio, accelerated the accumulation of mitochondrial reactive oxygen species (ROS) and downregulated the signal pathways governing energy metabolism and mitochondrial biogenesis while Cldn5 reversed these metabolic defects. Besides, knockdown of Cldn5 in the mouse left ventricular myocardium via shRNA adeno-associated virus (AAV) led to arrhythmia, myocardial atrophy, cardiac fibrosis and increased mortality. Proteomic analysis revealed that Cldn5 knockdown resulted in 43 differential expressed proteins (DEPs) that disrupt key metabolic pathways. Furthermore, we observed downregulated Cldn5 in the left ventricular myocardium after myocardial infarction (MI). AAV-mediated overexpression of Cldn5 significantly protected the heart against ischemic injury by reducing infarct size, preserving mitochondrial number, decreasing ADP/ATP ratio and mitochondrial ROS production, and enhancing the signal of energy metabolism and mitochondrial biogenesis. Mechanistically, we show that Cldn5 regulates the AMPK/ACC energy sensing pathway and the PGC-1α/NRF1/TFAM mitochondrial biogenesis axis. These findings unveil a non-canonical role for Cldn5 as a crucial regulator of mitochondrial bioenergetics and suggest that targeting Cldn5 may offer a novel therapeutic strategy for ischemic heart disease.
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9. PARP7 drives angiotensin II-induced vascular remodeling via ADP-ribosylation and inhibition of GPX4.
9. PARP7通过ADP-核糖基化及抑制GPX4驱动血管紧张素II诱导的血管重构PMID:日期:2026-09-24Pathological vascular remodeling is driven by metabolic imbalance in vascular smooth muscle cells (VSMCs). NAD homeostasis is essential for sustaining VSMC contractility, quiescence, and genomic stability. ADP-ribosylation, catalyzed by poly(ADP-ribose) polymerase (PARP) enzymes, is an NAD-dependent modification that links NAD consumption to cellular stress. Here, we identify the mono-ADP-ribosyltransferase PARP7 as a critical regulator of vascular remodeling, with elevated expression in VSMCs. Parp7 deficiency attenuates angiotensin II-induced remodeling, while VSMC-specific overexpression exacerbates it. Mechanistically, PARP7 binds GPX4 via its WWE domain, and GPX4 mono-ADP-ribosylation depends on the catalytic activity of H532 in PARP7. This modification suppresses GPX4 activity and promotes VSMC ferroptosis. These findings establish a VSMC-specific PARP7-GPX4 axis in vascular remodeling and highlight PARP7 as a potential therapeutic target in hypertensive vascular disease.
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10. GPAT3 protects against lipid stress-induced ferroptosis in hepatocellular carcinoma: From multi-omics analysis to functional validation.
10. GPAT3保护肝细胞癌免受脂质应激诱导的铁死亡：从多组学分析到功能验证PMID:日期:2026-09-24[中文摘要] 代谢相关肝细胞癌（HCC）的全球负担正在增加，肥胖已成为其关键致病因素。然而，将脂质代谢失调与HCC进展及治疗脆弱性联系起来的分子机制仍不清楚。我们分析了2021年全球疾病负担数据，以评估1990年至2021年归因于代谢风险的肝癌负担。采用孟德尔随机化评估代谢特征与肝癌风险之间的因果关联。整合TCGA、GTEx和GEO数据集以识别脂质应激反应性调控因子。利用公共数据集和组织芯片免疫组化评估临床相关性。在HCC细胞和高脂饮食喂养的同系小鼠肿瘤模型中进行功能验证。1990年至2021年，归因于代谢风险的肝癌死亡和伤残调整生命年显著增加。孟德尔随机化显示，肥胖相关特征（包括BMI、腰围和体脂百分比）与肝癌风险存在因果关联，而血糖特征则无此关联。生物信息学筛选鉴定出GPAT3是一种脂质代谢调控因子，在HCC中表达上调，由棕榈酸诱导，与不良预后相关，并在BMI较高的患者中富集。组织芯片分析证实HCC中GPAT3蛋白表达增加，且与较高BMI和GPX4表达相关。GPAT3缺失使HCC细胞对棕榈酸诱导的铁死亡敏感，而Fer-1挽救和GPAT3过表达支持其保护作用。在体内，FSG67增强了索拉非尼相关的抗肿瘤效果并增加了肿瘤脂质过氧化。GPAT3保护HCC细胞免受脂质应激诱导的铁死亡，是肥胖相关HCC中潜在的代谢脆弱性靶点。
[英文摘要] The global burden of metabolic-associated hepatocellular carcinoma (HCC) is increasing, with obesity emerging as a key causal factor. However, the molecular mechanisms linking lipid metabolic dysregulation to HCC progression and therapeutic vulnerability remain unclear. We analyzed Global Burden of Disease 2021 data to assess liver cancer burden attributable to metabolic risks from 1990 to 2021. Mendelian randomization was used to evaluate causal associations between metabolic traits and liver cancer risk. TCGA, GTEx, and GEO datasets were integrated to identify lipid stress-responsive regulators. Clinical relevance was assessed using public datasets and tissue microarray immunohistochemistry. Functional validation was performed in HCC cells and a high-fat diet-fed syngeneic mouse tumor model. Liver cancer deaths and DALYs attributable to metabolic risks increased markedly from 1990 to 2021. Mendelian randomization showed that obesity-related traits, including BMI, waist circumference, and body fat percentage, were causally associated with liver cancer risk, whereas glycemic traits were not. Bioinformatics screening identified GPAT3 as a lipid metabolism regulator upregulated in HCC, induced by palmitic acid, associated with poor prognosis, and enriched in patients with higher BMI. Tissue microarray analysis confirmed increased GPAT3 protein expression in HCC and its association with higher BMI and GPX4 expression. GPAT3 depletion sensitized HCC cells to palmitic acid-induced ferroptosis, whereas Fer-1 rescue and GPAT3 overexpression supported its protective role. In vivo, FSG67 enhanced sorafenib-associated antitumor effects and increased tumor lipid peroxidation. GPAT3 protects HCC cells from lipid stress-induced ferroptosis and represents a potential metabolic vulnerability in obesity-associated HCC.