Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Proteomic Biomarker Discovery in Breast Cancer: Advances, Challenges, and Translational Prospects.","authors":"Mahan Hassani, Iman Morshedi, K J Matmurotov, Isanova Shoira Tulkinovna, Abdullaev Makhmudjon Mukhamedovich, Mahdieh Khorsandi, Abdiyev Rasul Ernazar Ugli, Tianyao Yang, Xi Lin","doi":"10.1002/jbt.71049","DOIUrl":"10.1002/jbt.71049","url":null,"abstract":"<p><p>Breast cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Despite major progress in genomic classification, molecular pathology, and targeted therapy, the identification of clinically reliable proteomics-derived biomarkers for early detection, prognostic stratification, treatment response prediction, and longitudinal monitoring remains an unresolved translational challenge. Recent studies have applied proteomic profiling to breast cancer tissues and clinically accessible biofluids, including serum, plasma, saliva, nipple aspirate fluid, urine, and extracellular vesicle-enriched fractions, to identify protein signatures with potential diagnostic and therapeutic relevance. Contemporary platforms, including LC-MS/MS, data-independent acquisition mass spectrometry, multiplexed quantitative proteomics, targeted proteomics using multiple reaction monitoring and parallel reaction monitoring, spatial proteomics, and affinity-based high-throughput assays such as Olink and SomaScan, have expanded the analytical depth and clinical scalability of breast cancer biomarker research. However, many candidate biomarkers remain confined to discovery or early verification stages because of limited analytical sensitivity, insufficient specificity, inter-platform variability, small and heterogeneous cohorts, incomplete external validation, and uncertainty regarding clinical utility beyond established pathological markers. This review critically evaluates current proteomic technologies and proteomics-derived biomarker candidates in breast cancer, distinguishes discovery-level findings from clinically validated evidence, and discusses the major methodological, regulatory, and implementation barriers that continue to limit translation into routine oncology practice. Greater emphasis on standardized workflows, targeted verification, multi-center validation, and clinically actionable biomarker panels will be essential for integrating proteomics into precision breast cancer care.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71049"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effect of Isoflurane on Hypoxia/Reoxygenation-Induced Myocardial Injury via miR-548a-5p Regulation of PTEN.","authors":"Ji Yao, Jianyong Zheng, Wei Wei","doi":"10.1002/jbt.71041","DOIUrl":"10.1002/jbt.71041","url":null,"abstract":"<p><p>Ischemia-reperfusion (I/R) injury induces cardiomyocyte apoptosis, oxidative stress and elevated myocardial injury markers. This study aimed to investigate whether the microRNA-548a-5p (miR-548a-5p)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN) axis mediates the cardioprotection conferred by isoflurane (ISO). An in vitro hypoxia/reoxygenation (H/R) injury model was established using H9c2 cardiomyocytes, including control, H/R and ISO pretreatment groups. We detected miR-548a-5p and PTEN expression by RT-qPCR, and evaluated cell viability, apoptosis, myocardial injury markers including creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and reactive oxygen species (ROS) using CCK-8, flow cytometry, ELISA and DCFH-DA staining. Dual-luciferase reporter assay validated the direct binding between miR-548a-5p and PTEN. H/R downregulated miR-548a-5p and upregulated PTEN, accompanied by decreased cell viability, increased apoptosis, myocardial injury and oxidative stress. 1.0% ISO pretreatment reversed these adverse alterations, restored miR-548a-5p and suppressed PTEN expression. miR-548a-5p inhibition attenuated ISO-elicited cardioprotection, whereas PTEN silencing restored the cardioprotective capacity compromised by miR-548a-5p inhibition. In conclusion, ISO exerts cardioprotective effects via the miR-548a-5p/PTEN signaling axis, offering a potential therapeutic target for I/R injury.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71041"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalin Protects Mouse Testis From Injury Induced by PM_2.5 Associated With the DKK1-Wnt/β-Catenin Signaling Pathway.","authors":"Lili Deng, Juan Wang, Shuyin Li, Yaping Mao, Ye Sun, Qiaoqiao Yang, Zhenghui Xie, Chen Zhang, Shuo Gong, Chunling Xiao, Mingyue Ma","doi":"10.1002/jbt.71057","DOIUrl":"10.1002/jbt.71057","url":null,"abstract":"<p><p>Fine particulate matter (PM_2.5) has a damaging effect on the male reproductive system. Baicalin has excellent anti-inflammatory and antioxidant pharmacological functions. The main purpose of this study was to investigate whether baicalin had a protective effect against PM_2.5-induced damage to the reproductive system of mice, and to further investigate the mechanism of the protective effect of baicalin. In our experiment, baicalin was administered by gavage 1 h before PM_2.5 exposure, followed by exposure to PM_2.5 with an oral-nasal exposure system at 750 μg/m³ for 4 h/day, and this experiment was continued for 45 days until the model was established. The results indicated that PM_2.5 exposure decreased testicular weight and organ coefficient, sperm count, and serum testosterone level, and down-regulated the mRNA and protein expressions of StAR, CYP11A1, and CYP17A1, which related to testosterone synthesis. After baicalin treatment, our experimental results showed that the 50 and 100 mg/kg baicalin groups showed a gradual increase in sperm counts, testosterone levels, and a significant restoration of genes and protein related to testosterone synthesis and the DKK1-Wnt/β-catenin signaling pathway. In conclusion, baicalin might play a protective role in promoting testicular tissue repair, and this may be associated with the regulation of the DKK1 - Wnt/β-catenin signaling pathway.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71057"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0044097 Serves as a Promising Biomarker of Atherosclerosis and Its Effects on Vascular Smooth Cell Proliferation and Migration","authors":"Cencen Ren,&nbsp;Yungen Jiao","doi":"10.1002/jbt.71031","DOIUrl":"10.1002/jbt.71031","url":null,"abstract":"<p>Atherosclerosis (AS) is closely related to the pathogenesis and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). To explore the value of hsa_circ_0044097 in the clinical management of AS and to elucidate its role and mechanism in the injury of VSMCs induced by in vitro oxidized low-density lipoprotein (ox-LDL). The mRNA expressions of hsa_circ_0044097 and miR-3918 were determined using RT-qPCR, and transfection verification was also conducted. The content of IL-6 and TNF-α was determined using an ELISA kit. CCK-8 and transwell assays were performed to determine the proliferation and migration of HASMC cells. The dual luciferase reporter assay and Spearman correlation analysis were performed to verify the relationship between hsa_circ_0044097 and miR-3918. The clinical value of hsa_circ_0044097 was evaluated using the ROC curve, K-M survival analysis and Cox analysis. Hsa_circ_0044097 level was decreased in AS patients' serum and HASMCs stimulated by ox-LDL. Hsa_circ_0044097 could serve as an indicator for the diagnosis of AS and for predicting the occurrence of MACE in AS patients. Overexpression of hsa_circ_0044097 inhibited the levels of inflammatory factors, cell proliferation and migration. MiR-3918 was targeted by hsa_circ_0044097, and overexpression of miR-3918 reversed the inhibitory effect of the upregulation of hsa_circ_0044097 on the proliferation and migration of VSMCs. Hsa_circ_0044097 may be a biomarker for diagnosing AS and predicting the occurrence of MACE. Hsa_circ_0044097 influences the progression of AS.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rupatadine Ameliorates Cisplatin-Induced Hepatotoxicity in Rats: Targeting HMGB1/TLR4/NF-κB and NLRP3/Caspase-1 Signaling Pathways","authors":"Shaimaa Mohamed Abdelrahman,&nbsp;Amany Abdlrehim Bekhit,&nbsp;Olivia N. Beshay","doi":"10.1002/jbt.71050","DOIUrl":"https://doi.org/10.1002/jbt.71050","url":null,"abstract":"<p>Despite cisplatin (CISP) is broadly employed in cancer therapy, its adverse effects, involving hepatotoxicity, restrict its clinical usage. Thus, this study was designed to explore the prospect of repurposing rupatadine (RUPA), a dual antagonist of histamine and platelet-activating factor (PAF), against CISP-evoked hepatotoxicity in rats. Rats were <i>i.p</i>. injected with CISP (6 mg/kg) for the induction of hepatotoxicity on the 8th day of the study in the presence and absence of RUPA in two dosages (3, 6 mg/kg) orally for 14 days. Different biochemical parameters and histopathological assessments, along with the mechanistic characterizations of the possible protective impact of the RUPA were conducted. Administration of CISP evoked hepatic histopathological modifications and raised serum liver enzyme levels and hepatic MDA content, PAF, and histamine levels, along with diminishing the serum albumin level, hepatic SOD activity, and GSH level. Moreover, CISP remarkably augmented the levels of HMGB1, TLR4, p-NF-κB p65, IL-6, TNF-α, IL-18, IL-1β, NLRP3, and cleaved caspase-1 proteins with an evident decline in the level of IL-10. On the contrary, pretreatment with either RUPA.3 or RUPA.6 dramatically ameliorated these alterations triggered by CISP injection. RUPA counteracts hepatotoxicity evoked by CISP in rats via its anti-oxidative as well as anti-inflammatory properties via repression of hepatic HMGB1/TLR4/NF-κB and thus restricts the activation of NLRP3/caspase-1 signaling cascade.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Anti-Inflammatory Effects of Alternate Day Fasting via TLR4 and Leptin Signaling in Middle-Aged Rats","authors":"Ozgen Kilic-Erkek,&nbsp;Gulsah Gundogdu,&nbsp;Abdullah Coguplugil,&nbsp;Yavuz Dodurga","doi":"10.1002/jbt.71051","DOIUrl":"https://doi.org/10.1002/jbt.71051","url":null,"abstract":"<p>Alternate-day fasting (ADF) may exert age-related anti-inflammatory effects by modulating key metabolic and immune pathways. This study aimed to investigate the sex-specific effects of ADF on inflammation in middle-aged male and female rats and focused on the Toll-like receptor 4 (TLR4) and leptin signaling pathways. A total of 32 rats (16 males, 16 females; 14 months old) were assigned to four groups (<i>n</i> = 8): ad libitum-fed and ADF groups for each sex. The ADF protocol consisted of 24-h fasting every other day for 2 months. Serum and hypothalamic samples were analyzed via ELISA to measure triglyceride, total cholesterol, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), suppressor of cytokine signaling 3 (SOCS3), leptin, and ObRb levels. TLR4 gene expression in the brain and liver was assessed via qRT–PCR. Two months of ADF significantly reduced body weight and retroperitoneal fat mass compared with those of the control groups (<i>p</i> &lt; 0.001). Cumulative food intake and fasting glucose levels decreased in both sexes following ADF (<i>p</i> &lt; 0.001), and serum triglyceride, total cholesterol, TNF-α, and IL-6 levels (<i>p</i> &lt; 0.001) were significantly reduced. Hypothalamic SOCS3 and leptin levels decreased, whereas ObRb expression increased (<i>p</i> &lt; 0.05). Additionally, TLR4 gene expression was significantly downregulated in both tissues (<i>p</i> &lt; 0.001). These findings suggest that ADF is associated with reduced age-related inflammation and alterations in the TLR4 and leptin signaling pathways. The observed downregulation of SOCS3 and upregulation of ObRb indicate enhanced leptin sensitivity, highlighting ADF as a promising strategy to counteract sex-specific aging-related inflammation and leptin resistance.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apigenin, Selenium, and Combinations Are Effective in Preventing 5-Fluorouracil Induced Cardiovascular Damage","authors":"Gözde Atila Uslu,&nbsp;Hamit Uslu,&nbsp;Taha Abdulkadir Çoban,&nbsp;Emine Toraman,&nbsp;Mustafa Özkaraca","doi":"10.1002/jbt.71028","DOIUrl":"https://doi.org/10.1002/jbt.71028","url":null,"abstract":"<p>Although chemotherapy is still a widely used primary treatment modality for many cancers, it is an accepted fact that it causes many undesirable side effects and toxicity. Until a new, side-effect-free treatment modality is developed, new resources will continue to be sought to prevent and reduce the adverse effects of chemotherapy. In this study, we investigated the potential of apigenin, selenium, and their combination to prevent cardiovascular toxicity induced by 5-fluorouracil (5FU), an important chemotherapeutic agent. The study consisted of control (C), 5FU, apigenin + 5FU (Api + 5FU), selenium + 5FU (Se + 5FU), and apigenin + selenium + 5FU (Api + Se + 5FU) groups. Api (50 mg/kg) and Se (0.5 mg/kg) were administered orally to rats for 7 days. On Day 5, 5FU was administered i.p. at a dose of 150 mg/kg. Administration of 5FU significantly reduced GSH levels and CAT and TrxR activities in both cardiac and thoracic aortic tissues. It also decreased Bcl-2 expression and increased Bax and Caspase-3 expression in cardiac tissue, while reducing Bcl-2 and increasing Bax expression in the thoracic aorta. Thoracic aortic MDA levels were also significantly elevated. On the contrary, oxidative stress and apoptosis were significantly decreased, and cardiovascular damage was attenuated in apigenin and selenium treated groups. In this study, it was determined that 5FU caused a higher level of toxicity to the heart compared to the thoracic aorta. In addition, both apigenin and selenium were shown to have significant protective effects on the cardiovascular system against 5FU toxicity. However, the cardiovascular protection against 5FU toxicity was found to be higher when apigenin and selenium were used together.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SDCBP Cooperates With YBX1 to Promote ESCC Metastasis by Forming a Positive Feedback Loop With Wnt-β-Catenin Signaling Pathway","authors":"Ruijuan Du,&nbsp;Bo Bian,&nbsp;Manyu Luo,&nbsp;Chen Yuan,&nbsp;Kelei Guo,&nbsp;Kai Li,&nbsp;Hui Zhang,&nbsp;Guangji Zhang,&nbsp;Li Han","doi":"10.1002/jbt.71046","DOIUrl":"10.1002/jbt.71046","url":null,"abstract":"<p>Syndecan binding protein (SDCBP) has been shown to be upregulated in esophageal squamous cell carcinoma (ESCC) and predicts poor prognosis in our previous research. SDCBP stimulated the proliferation and tumor formation and may be a target for ESCC. However, the participation of SDCBP in epithelial–mesenchymal transition (EMT) and ESCC metastasis is unclear. In this study, we found that SDCBP promoted the EMT process of ESCC cells and facilitated ESCC metastasis both in vitro and in vivo. Mechanically, SDCBP was found to influence the activation of the Wnt-β-catenin pathway. β-catenin expression and nuclear localization were regulated by SDCBP, accompanied by altered expression of Wnt-β-catenin pathway target genes. Additionally, SDCBP interacted with Y-box binding protein 1 (YBX1) and abnormally upregulated YBX1 in ESCC was responsible for SDCBP-mediated regulation of ESCC migration and invasion. Finally, SDCBP was identified to be transcriptionally regulated by the Wnt-β-catenin pathway. Thus, our study provides a better understanding of the SDCBP-YBX1-Wnt-β-catenin axis in ESCC metastasis and explores a positive feedback loop between SDCBP and the Wnt-β-catenin pathway, offering more compelling evidence for employing SDCBP as a target for ESCC treatment.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Goniothalamin as a Styryl-Lactone Toxicophore in Cancer Models: Electrophile-Driven DNA Damage, Reactive Oxygen Species–Endoplasmic Reticulum Stress Signaling and Detoxification-Relevant Safety Considerations","authors":"Nataša Joković,&nbsp;Strahinja Pešić,&nbsp;Marija Novaković,&nbsp;Anđela Dubroja Krstić,&nbsp;William N. Setzer,&nbsp;Javad Sharifi-Rad,&nbsp;Daniela Calina","doi":"10.1002/jbt.71040","DOIUrl":"10.1002/jbt.71040","url":null,"abstract":"<p>Goniothalamin (GTN), a natural styryl-lactone from the <i>Goniothalamus</i> genus, has demonstrated cytotoxic properties against a variety of human cancer cell lines with minimal effects on normal cells. Its traditional medicinal use and preliminary preclinical evidence suggest potential as a selective anticancer agent. The purpose of this review is to summarize the preclinical anticancer activity, molecular mechanisms, and therapeutic potential of GTN and its semi-synthetic derivatives across cancer cell lines and animal models. A comprehensive literature search was conducted on the anticancer effects of GTN using databases including PubMed, Scopus, and ScienceDirect. Studies reporting <i>in-vitro</i> cytotoxicity, half-maximal inhibitory concentration (IC50) values, mechanisms of action, synergistic drug effects, and in-vivo antitumor efficacy were included. Data on GTN enantiomers and semisynthetic derivatives were also analyzed. GTN exhibited potent, dose- and time-dependent cytotoxicity in breast, colorectal, hepatoma, leukemia, and other cancer cell lines (IC₅₀ in the low micromolar range), while sparing normal cells. Mechanistically, GTN induced DNA damage, reactive oxygen species (ROS) generation, cell cycle arrest, endoplasmic reticulum stress, apoptosis, autophagy, necroptosis, and anoikis. The anticancer activity of GTN enantiomers appears to be cell-line dependent: although the (R)-enantiomer showed higher potency in several cancer models, the (S)-enantiomer displayed greater activity in selected cancer cell lines. GTN synergized with chemotherapeutics such as paclitaxel, vinblastine, and cisplatin, enhancing apoptosis and reducing cell viability. Semi-synthetic derivatives, including methoxy- and nitro-substituted analogs, demonstrated enhanced potency and selectivity. In animal models, GTN exhibited antitumor activity without detectable toxicity. GTN is a promising natural anticancer agent with multimodal mechanisms of action and selective cytotoxicity. Semisynthetic derivatives further improve its potency and specificity. Further in-vivo studies, bioavailability, and pharmacokinetic investigations are warranted to advance GTN towards clinical application.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial Lipid Metabolism Imbalance: The Pathological Core and Novel Diagnostic-Therapeutic Directions of Cardiovascular Diseases","authors":"Peiyun Xie,&nbsp;Qun Zeng,&nbsp;Hongrui Wang,&nbsp;Meihua She","doi":"10.1002/jbt.71033","DOIUrl":"10.1002/jbt.71033","url":null,"abstract":"<p>Cardiac lipid metabolism is fundamental to myocardial energy homeostasis, with fatty acid oxidation (FAO) supplying the majority of ATP in the healthy adult heart. This review synthesizes the core regulatory network governing cardiac lipid metabolism, encompassing lipid droplet dynamics mediated by perilipins (e.g., Plin5, Plin2), fatty acid uptake via CD36, systemic lipid modulation by apolipoproteins (e.g., APOC3), and the central energy-sensing AMPK/PGC-1α/PPARα axis. Dysregulation of this network initiates a self-perpetuating lipotoxic cycle, characterized by the accumulation of toxic lipid intermediates (e.g., diacylglycerols, ceramides), oxidative stress, and inflammatory activation, which serves as a common pathological mechanism across diverse cardiovascular diseases (CVDs), including atherosclerosis, heart failure, diabetic cardiomyopathy, and ischemic injury. Emerging from this mechanistic understanding is a promising landscape of biomarkers—such as specific ceramide species, the ApoB/ApoA-1 ratio, and circulating perilipins—and targeted therapeutic strategies, including APOC3 inhibitors, SGLT2 inhibitors, and Plin5-directed therapies. Future advances will depend on integrating multi-omics technologies and precision medicine approaches to tailor interventions to specific metabolic phenotypes, thereby opening new avenues for the prevention and treatment of CVDs.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}