Biomolecules最新文献

{"title":"The Development of Squid Ink Melanin Nanoparticles as a Multifunctional Colorant Anchored on Hair Fibers: Preparation, Physicochemical Characterization and Dyeing Performance.","authors":"Ao Cai, Hetong Lin, Yushuang Li, Dan Li, Kaikai Bai, Junde Chen","doi":"10.3390/biom16040573","DOIUrl":"10.3390/biom16040573","url":null,"abstract":"<p><p>Traditional chemical hair dyes are associated with potential health risks, while botanical alternatives are often hampered by poor stability and limited color longevity. In this study, discarded squid ink was used to prepare bionic hair colorants of high performance. By synergizing ultrasound disruption with enzymatic hydrolysis, the crude ink aggregates were transformed into highly uniform squid ink melanin nanoparticles (SIMNPs) with size and zeta potential of ~174 nm and -37.5 mV, respectively. This effectively improved the solubility but reduced the steric limitation of natural melanin. To overcome the weak affinity between melanin and human hair, a biomimetic interface where Fe(III) ions act as supramolecular bridges was further engineered to stably bind the SIMNPs to hair keratin. Under optimized conditions (pH 8.0, 45 °C, and 80 min), the dyed hair achieved a natural deep black with a total color difference (ΔE*) of 68.79 ± 0.29, which was maintained at 63.19 ± 0.27 even after 13 consecutive water washing cycles. Unlike destructive oxidative dyes, this SIMNP dyeing system assisted by coordination-driven assembly preserved the native α-helical architecture and disulfide bond networks of hair keratin. Furthermore, the deposited SIMNP layer effectively protected hair fibers from ultraviolet (UV) damage due to its powerful UV-shielding capacity. Crucially, in vitro and in vivo evaluations confirmed the exceptional biosafety of this formulation, demonstrating robust cellular tolerance and absence of murine skin irritation. The work demonstrates a green, low-damage paradigm for the development of bio-based hair colorants of high performance and presents a promising pathway for the high-value utilization of marine by-products.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteoglycan Dynamics and Bone Quality: Molecular Regulation to Age-Related Fragility.","authors":"Savannah Heath, Rui Hua, Xiaodu Wang, Jean Jiang","doi":"10.3390/biom16040572","DOIUrl":"10.3390/biom16040572","url":null,"abstract":"<p><p>Clinically, bone mineral density (BMD) accounts for only approximately 50% of the observed variance in bone fragility fractures. This review examines the dynamic and mechanistic role of the non-collagenous organic matrix, specifically proteoglycans (PGs) and glycosaminoglycans (GAGs), in maintaining bone toughness and bone quality. During aging, bulk cortical GAG levels decrease by up to ~17% and are highly associated with reduced bone tissue toughness. We analyze how this age-related loss may arise from uncoupled bone remodeling and tissue aging, including the accumulation of older, interstitial tissue and dysregulated osteocyte-mediated matrix maintenance. We then discuss the functional importance of PG/GAG composition, maturation, and catabolism and how perturbations in these processes can promote pro-inflammatory signaling that accelerates matrix degradation and contributes to systemic aging. Lastly, we discuss potential interventions to preserve or restore GAGs/PGs in bone and improve overall bone quality.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant Attenuated <i>Salmonella</i> Enteritidis Vector Enhances the Immunogenicity of <i>Clostridium perfringens</i> EntB Antigen for Effective Prevention of Avian Necrotic Enteritis.","authors":"Wenjing Li, Yu-An Li, Xiaolong Liu, Haiping Xie, Jingyi Zhao, Yi Feng, Huoying Shi","doi":"10.3390/biom16040575","DOIUrl":"10.3390/biom16040575","url":null,"abstract":"<p><p>Necrotizing enteritis (NE) is an important intestinal disease threatening the poultry farming industry, and the ban on antibiotic growth promoters has created an urgent demand for safe and effective NE vaccines. Recombinant attenuated <i>Salmonella</i> vectors (RASVs) administered orally can induce mucosal immune responses against delivered antigens, thus showing great potential to elicit protective immunity against NE. The EntB protein is a newly discovered putative enterotoxin of <i>Clostridium perfringens</i> (<i>C. perfringens</i>). Bioinformatic predictions in this study revealed that EntB contains nineteen potential antigenic epitopes, two functional domains (NlpC and YgiM), and interacts with ten proteins, supporting its potential as a target antigen for NE vaccines. To optimize the immunogenicity of EntB-based vaccines, we constructed a novel recombinant attenuated <i>Salmonella</i> Enteritidis (<i>S.</i> Enteritidis) vector rSC0169 harboring a rhamnose-regulated delayed attenuation system, which was then used to deliver EntB to generate the recombinant strain rSC0169(pS-EntB). This system enhanced the immunogenicity of the <i>Salmonella</i> vector rSC0169 and further elicited robust mucosal immune responses against EntB, as well as humoral and cellular immune responses. Compared with the control strain rSC0169(pS0018), rSC0169(pS-EntB) candidate vaccine strain significantly alleviated NE symptoms, increased the intestinal villus height/crypt depth (VH/CD) ratio, upregulated tight junction protein expression, and reduced excessive pro-inflammatory cytokine production. In conclusion, this study provides a promising NE candidate vaccine and offers a valuable strategy for developing vaccines against other intestinal bacterial diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.","authors":"Kai-Li Liu, Shuo Zhang, Feng-Shuo Li, Min-Jin Chen, Yuan-Yuan Chen, Ning Zhang, Kai Wang","doi":"10.3390/biom16040574","DOIUrl":"10.3390/biom16040574","url":null,"abstract":"<p><p>The polyamine metabolic pathway, an evolutionarily conserved nexus integrating nutrient sensing, translation control, and cellular proliferation, is fundamentally rewired in cancer. Melanoma, a malignancy of melanocytes notorious for its metastatic propensity and therapy resistance, exhibits a profound dependency on this pathway, extending beyond mere polyamine abundance to the specialized function of their derivative, hypusine. This review synthesizes cutting-edge insights into the deoxyhypusine synthase (DHPS)/eukaryotic initiation factor 5A (eIF5A) hypusination circuit as a critical amplifier of oncogenic signaling in melanoma. We dissect its role as a translational rheostat for pro-tumorigenic proteomes, a driver of phenotypic plasticity underpinning invasion and vasculogenic mimicry, and a modulator of the immunosuppressive tumor microenvironment. Moving beyond the classical inhibitor GC7, we explore the emergence of novel allosteric DHPS inhibitors with compelling preclinical efficacy. Finally, we propose a paradigm shift: targeting the DHPS/eIF5A axis represents a strategy to disrupt the \"non-oncogene addiction\" of melanoma-its reliance on hyperactive translation and adaptive survival mechanisms-offering a promising avenue alongside targeted therapies and immunotherapies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chirobiophore: A Novel Framework for Quantifying Biochirality in Macromolecular Systems.","authors":"Claudiu N Lungu, Subhash C Basak","doi":"10.3390/biom16040576","DOIUrl":"10.3390/biom16040576","url":null,"abstract":"<p><p>Chirality is a pervasive and functionally critical feature of biological macromolecules, yet its distributed and emergent forms remain poorly quantified in complex systems such as membrane proteins. We present Chirobiophore, a novel paradigm for capturing biochirality across scales-from atomic geometries to global structural asymmetries. Unlike traditional stereochemical metrics, Chirobiophore employs a multidimensional model-independent vector comprising Local Tetrahedral Asymmetry (LTA), Helical Path Curvature (HPC), Asymmetric Environment Score (AES), Directional Density Profile (DDP), Leaflet Asymmetry Index (LAI), and Orientation Twist Score (OTS). This framework enables coordinate-invariant comparisons of structurally diverse proteins in a continuous chirality space. We demonstrate its application to canonical, GPCR, and topologically complex membrane proteins, revealing distinct chirality signatures and functional clustering. Furthermore, we map Chirobiophore descriptors to tissue-level asymmetry indices, providing a bridge between molecular structure and morphogenetic patterning. Chirobiophore offers a unified, extensible platform for structural biology, synthetic design, and developmental modeling of chirality.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling Multilayered RNA Modification Networks in Female Reproduction and Obstetric/Gynaecologic Disorders.","authors":"Yujie Kuai, Yanjun Yi, Xinyu Li, Zhuangping Wang, Yan Zheng, Yuxuan Li, Yulin Li","doi":"10.3390/biom16040571","DOIUrl":"10.3390/biom16040571","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objective:&lt;/b&gt; RNA modifications, including N&lt;sup&gt;6&lt;/sup&gt;-methyladenosine (m&lt;sup&gt;6&lt;/sup&gt;A), 5-methylcytosine (m&lt;sup&gt;5&lt;/sup&gt;C), 7-methylguanosine (m&lt;sup&gt;7&lt;/sup&gt;G), N&lt;sup&gt;1&lt;/sup&gt;-methyladenosine (m&lt;sup&gt;1&lt;/sup&gt;A), pseudouridine (Ψ), N&lt;sup&gt;4&lt;/sup&gt;-acetylcytidine (ac&lt;sup&gt;4&lt;/sup&gt;C), 5-methoxycarbonylmethyl-2-thiouridine (mcm&lt;sup&gt;5&lt;/sup&gt;s&lt;sup&gt;2&lt;/sup&gt;U) and adenosine-to-inosine (A-to-I) editing, constitute a critical layer of post-transcriptional regulation that influences RNA stability, splicing, translation and degradation. This review aims to systematically summarise the current understanding of the molecular mechanisms and regulatory networks of RNA modifications in the female reproductive physiology and to evaluate their pathological implications in obstetric and gynaecologic disorders. &lt;b&gt;Methods:&lt;/b&gt; We conducted a comprehensive literature review, synthesising findings from high-throughput sequencing studies, functional experiments and clinical investigations. The review integrates evidence across multiple RNA modification types, their regulatory enzymes (writers, erasers and readers) and their roles in physiological processes (germ cell development, oocyte maturation, embryogenesis and endometrial function) and pathological conditions (gynaecologic cancers, preeclampsia, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency). &lt;b&gt;Results:&lt;/b&gt; RNA modifications function as dynamic and reversible regulators that orchestrate key reproductive events, including primordial germ cell differentiation, oocyte meiosis, the maternal-to-zygotic transition, the establishment of uterine receptivity, and placental development. These modifications operate through coordinated writer-eraser-reader networks that fine tune transcripts' stability, translation efficiency and RNA decay. The dysregulation of these epitranscriptomic networks is strongly implicated in the pathogenesis of gynaecologic malignancies (cervical, ovarian, endometrial cancers and choriocarcinoma), pregnancy-related disorders (preeclampsia, gestational diabetes mellitus and recurrent miscarriage), reproductive endocrine disorders (polycystic ovary syndrome and premature ovarian insufficiency) and benign gynaecological conditions (endometriosis and adenomyosis). Emerging evidence also reveals complex crosstalk among RNA modifications, such as cooperative interactions between m&lt;sup&gt;6&lt;/sup&gt;A and m&lt;sup&gt;5&lt;/sup&gt;C in translation regulation and antagonistic relationships between m&lt;sup&gt;6&lt;/sup&gt;A and A-to-I editing. &lt;b&gt;Conclusions:&lt;/b&gt; RNA modifications represent an essential and multifaceted regulatory layer in female reproduction, with broad implications for disease pathogenesis. Their unique reversibility and context-dependent functions offer promising opportunities for the development of diagnostic biomarkers and targeted therapeutic interventions. Future researchers should prioritise integrated multi-omics approaches, enhanced human-relevant models and clinical","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variecolactone, a Natural PDE4 Inhibitor from Marine-Derived <i>Talaromyces</i> sp. ZSD-1, Alleviates Amyloid-β Accumulation and mtDNA Dyshomeostasis via cAMP-PKA-CREB Signaling Pathway.","authors":"Tingting Fu, Yujia Shi, Zhonglin Yang, Juan Zhou, Ling Huang, Ying Fu, Wandi Xiong","doi":"10.3390/biom16040570","DOIUrl":"10.3390/biom16040570","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by amyloid-β deposition, neuroinflammation, and mitochondrial dysfunction. Phosphodiesterase 4 (PDE4), a key regulator of cyclic nucleotides in neurons, represents a promising therapeutic target for AD. In this study, we performed a PDE4 inhibition-guided screen of an in-house marine natural product library derived from marine fungi, leading to the identification of a sesterterpenoid variecolactone (VLT) as a potent PDE4 inhibitor. VLT exhibited selective PDE4D inhibition (IC₅₀ = 2.302 μM) with minimal activity against other PDE subtypes. Further mechanical investigation revealed that VLT treatment elevated cAMP and p-CREB levels, reduced amyloid-β (Aβ) accumulation, promoted synaptic function, and ameliorated mitochondrial fragmentation, along with mtDNA homeostasis in the AD cell model. Moreover, under conditions of mtDNA depletion or Drp1 overexpression, VLT exerted neuroprotective effects and maintained mtDNA homeostasis via the cAMP-PKA-CREB signaling pathway. These results demonstrate that PDE4 inhibition by VLT represents a promising therapeutic strategy for AD and related neurodegenerative disorders.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predominance of Biliverdin over Bilirubin in Human Seminal Plasma.","authors":"Nina Hojnik, Paola Sist, Sabina Passamonti, Borut Kovačič, Federica Tramer","doi":"10.3390/biom16040569","DOIUrl":"10.3390/biom16040569","url":null,"abstract":"<p><p>Biliverdin (BV) and bilirubin (BR) are established endogenous antioxidants and immune modulators in other organ systems; however, their roles in the male genital tract remain undefined. The aim of this study was to quantify both bile pigments in human seminal plasma using a fluorescent protein biosensor and to examine their associations with basic semen parameters. We analyzed forty-two semen samples from men undergoing infertility evaluation. Biliverdin predominated over bilirubin in 88.1% of samples. Biliverdin concentration ranged from 51.8 to 611.2 nM, whereas bilirubin ranged from 19.7 to 240.7 nM. The mean total amounts per ejaculate were 1054 pmol for biliverdin and 280 pmol for bilirubin. The total amount of bilirubin in the ejaculate was positively correlated with total sperm count (Rs = 0.47; <i>p</i> = 0.028), whereas biliverdin showed no significant association (Rs = 0.21; <i>p</i> = 0.723). Oligozoospermic samples had significantly lower bilirubin concentrations (<i>p</i> < 0.001) and lower total bilirubin amounts (<i>p</i> < 0.005). Teratozoospermic samples exhibited significantly higher biliverdin concentrations (<i>p</i> < 0.05). This study provides the first simultaneous quantification of biliverdin and unconjugated bilirubin in human seminal plasma and identifies distinct associations with sperm quality. These findings suggest that bile pigments may reflect localized redox-related processes in the male genital tract and may influence male fertility potential.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Barriers and Optimization Strategies for Remote Ischemic Conditioning to Enhance Stroke Cerebroprotection.","authors":"Xin Zhang, Jiaxin An, Xiaofeng Guo, Jiayu Li, Ruimin Wang","doi":"10.3390/biom16040568","DOIUrl":"10.3390/biom16040568","url":null,"abstract":"<p><p>Remote ischemic conditioning (RIC) is an endogenous strategy that mitigates cerebral injury in preclinical stroke models. However, its bench-to-bedside translation is frequently hindered by complex patient environments that induce RIC resistance and limit its neuroprotective efficacy. To bridge this translational gap, this review systematically examines the extrinsic pathophysiological and pharmacological barriers to RIC. We categorize RIC resistance into three mechanism-driven phenotypes. Impaired signal initiation (Type I) is often linked to diabetic sensorimotor polyneuropathy and the reactive oxygen species-scavenging effects of propofol. Signal transmission blockade (Type II) is associated with specific P2Y12 inhibitors and smoking-induced endothelial dysfunction. Furthermore, effector desensitization (Type III) involves target-organ unresponsiveness exacerbated by aging, chronic hyperglycemia, and postmenopausal estrogen depletion. To address these barriers, potential phenotype-specific optimization strategies are discussed. Ultimately, transitioning from generalized empirical protocols to mechanism-based precision strategies may help bypass RIC resistance in clinical settings and enhance stroke cerebroprotection.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of <i>N</i>-Acetylation on DNA Damage and Oxidative Stress Responses in Mammalian Cells and Human Hepatocytes Treated with Hydralazine.","authors":"Mariam R Habil, Makayla A Stephens, Alexandra A Cass, Elise M Mittlestat, Darbie Kwon, Alexandra Ellison, J Calvin Kouokam, David W Hein","doi":"10.3390/biom16040562","DOIUrl":"10.3390/biom16040562","url":null,"abstract":"<p><p>Hydralazine is widely used to treat hypertension during pregnancy and has epigenetic effects in cancer therapy. Cryoplatable human hepatocytes showed concentration-dependent increase in DNA damage response (linear trend <i>p</i> = 0.0069) following 24 h hydralazine treatment. DNA repair-deficient UV5 Chinese hamster ovary (CHO) cell lines expressing human <i>CYP1A2</i> and either <i>NAT2*4</i> (reference allele) or <i>NAT2*5</i> (variant allele) were treated with hydralazine for 24 h. CHO cells expressing <i>NAT2*4</i> showed a higher acetylation rate than those with <i>NAT2*5</i> (<i>p</i> < 0.001), whereas CHO cell viability did not differ significantly following hydralazine treatment (<i>p</i> > 0.05). Hydralazine caused a concentration-dependent increase in DNA damage response in the un-transfected UV5 CHO cell line, as well as in each of the UV5 CHO cell lines transfected with human <i>CYP1A2</i> and/or <i>NAT2</i> alleles. CHO cells with <i>CYP1A2</i> only showed higher DNA damage response from hydralazine compared to cells with <i>CYP1A2</i>/<i>NAT2*4</i> or <i>CYP1A2</i>/<i>NAT2*5</i> (<i>p</i> < 0.05 and <i>p</i> < 0.0001, respectively), and higher in <i>CYP1A2/NAT2*4</i> versus <i>CYP1A2/NAT2*5</i> cells (<i>p</i> = 0.0011). Apurinic/apyrimidinic (AP) sites in CHO cells expressing only <i>CYP1A2</i> were significantly higher than in the un-transfected UV5 CHO cell line (<i>p</i> < 0.01) and higher in CHO cells expressing <i>CYP1A2</i>/<i>NAT2*4</i> compared to <i>CYP1A2</i>/<i>NAT2*5</i>, but the difference was not significant (<i>p</i> > 0.05). In contrast, ROS levels were reduced following hydralazine treatment in CHO cells with <i>CYP1A2</i>/<i>NAT2*4</i> and <i>CYP1A2</i>/<i>NAT2*5</i> (<i>p</i> < 0.001 and <i>p</i> < 0.05, respectively). The results of the current study document DNA damage responses associated with hydralazine in human hepatocytes and CHO cells. The DNA damage response was increased following <i>N</i>-hydroxylation by CYP1A2, which competes with <i>N</i>-acetylation by NAT2.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}