BiomoleculesPub Date : 2025-05-14DOI: 10.3390/biom15050719
Shi-Yan Lai, Xiao-Juan Zhu, Wei-Dong Sun, Shuang-Zhou Bi, Chen-Ying Zhang, An Liu, Jiang-Hua Li
{"title":"Nicotinamide N-Methyltransferase (NNMT) and Liver Cancer: From Metabolic Networks to Therapeutic Targets.","authors":"Shi-Yan Lai, Xiao-Juan Zhu, Wei-Dong Sun, Shuang-Zhou Bi, Chen-Ying Zhang, An Liu, Jiang-Hua Li","doi":"10.3390/biom15050719","DOIUrl":"https://doi.org/10.3390/biom15050719","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, remains a global health challenge with limited therapeutic options and high mortality rates. Despite advances in understanding its molecular pathogenesis, the role of metabolic reprogramming in HCC progression and therapy resistance demands further exploration. Nicotinamide N-methyltransferase (NNMT), a metabolic enzyme central to NAD<sup>+</sup> and methionine cycles, has emerged as a critical regulator of tumorigenesis across cancers. However, its tissue-specific mechanisms in HCC-particularly in the context of viral hepatitis and methionine cycle dependency-remain understudied. This review systematically synthesizes current evidence on NNMT's dual role in HCC: (1) driving NAD<sup>+</sup> depletion and homocysteine (Hcy) accumulation via metabolic dysregulation, (2) promoting malignant phenotypes (proliferation, invasion, metastasis, and drug resistance), and (3) serving as a prognostic biomarker and therapeutic target. We highlight how NNMT intersects with epigenetic modifications, immune evasion, and metabolic vulnerabilities unique to HCC. Additionally, we critically evaluate NNMT inhibitors, RNA-based therapies, and non-pharmacological strategies (e.g., exercise) as novel interventions. By bridging gaps between NNMT's molecular mechanisms and clinical relevance, this review provides a roadmap for advancing NNMT-targeted therapies and underscores the urgency of addressing challenges in biomarker validation, inhibitor specificity, and translational efficacy. Our work positions NNMT not only as a metabolic linchpin in HCC but also as a promising candidate for precision oncology.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-13DOI: 10.3390/biom15050713
Itzae Adonai Gutiérrez-Hurtado, Mayra Elizabeth García-Acéves, Yolanda Puga-Carrillo, Mariano Guardado-Estrada, Denisse Stephania Becerra-Loaiza, Víctor Daniel Carrillo-Rodríguez, Reynaldo Plazola-Zamora, Juliana Marisol Godínez-Rubí, Héctor Rangel-Villalobos, José Alonso Aguilar-Velázquez
{"title":"Past, Present and Future Perspectives of Forensic Genetics.","authors":"Itzae Adonai Gutiérrez-Hurtado, Mayra Elizabeth García-Acéves, Yolanda Puga-Carrillo, Mariano Guardado-Estrada, Denisse Stephania Becerra-Loaiza, Víctor Daniel Carrillo-Rodríguez, Reynaldo Plazola-Zamora, Juliana Marisol Godínez-Rubí, Héctor Rangel-Villalobos, José Alonso Aguilar-Velázquez","doi":"10.3390/biom15050713","DOIUrl":"https://doi.org/10.3390/biom15050713","url":null,"abstract":"<p><p>Forensic genetics has experienced remarkable advancements over the past decades, evolving from the analysis of a limited number of DNA segments to comprehensive genome-wide investigations. This progression has significantly improved the ability to establish genetic profiles under diverse conditions and scenarios. Beyond individual identification, forensic genetics now enables the inference of physical traits (e.g., eye, hair, and skin color, as well as body composition), biogeographic ancestry, lifestyle habits such as alcohol and tobacco use, and even the transfer of genital microbiomes post-coitus, among other characteristics. Emerging trends point to a future shaped by the integration of cutting-edge technologies, including CRISPR-Cas systems, artificial intelligence, and machine learning, which promise to further revolutionize the field. This review provides a thorough exploration of forensic genetics, tracing its evolution from its foundational methods (past) to its diverse modern applications (present) and offering insights into its potential future directions.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-13DOI: 10.3390/biom15050712
Avanthika Mekala, Hongyu Qiu
{"title":"Interplay Between Vascular Dysfunction and Neurodegenerative Pathology: New Insights into Molecular Mechanisms and Management.","authors":"Avanthika Mekala, Hongyu Qiu","doi":"10.3390/biom15050712","DOIUrl":"https://doi.org/10.3390/biom15050712","url":null,"abstract":"<p><p>Vascular dysfunction frequently coexists with neurodegenerative disorders such as dementia and Alzheimer's disease (AD) in older individuals; however, the cause-and-effect relationship remains unclear. While AD is primarily characterized by neural tissue degeneration, emerging evidence suggests that aging-induced vascular dysfunction contributes to both the onset and progression of cognitive impairment and dementia by decreasing cerebral blood flow (CBF) and disrupting the blood-brain barrier (BBB). This challenges the traditional notion and underscores vascular dysfunction as an early pathogenic stimulus; thus, targeting vascular pathologies could be a promising strategy to slow dementia progression and potentially prevent AD. Conversely, aging-related neurodegeneration exacerbates vascular dysfunction, accelerating dementia pathology through oxidative stress and inflammation as well as deposition of neurotoxic substances such as beta-amyloid (Aβ) and tau in vascular walls. This bidirectional interaction creates a vicious cycle that worsens cognitive decline, underscoring the complexity of these diseases. This review aims to highlight recent advances in research on the mechanisms of aging-related vascular dysfunction in neurodegenerative diseases, focusing on vascular contributions to cognitive impairment and dementia (VCID) and AD. Additionally, we will explore the reciprocal effects and intricate relationship between vascular dysfunction and neurodegenerative pathologies, enhancing our understanding of relative disease pathogenesis and guiding the development of innovative prevention and treatment strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-13DOI: 10.3390/biom15050715
Alba Guglielmo, Alessandro Borghi, Corrado Zengarini, Bianca Maria Piraccini, Monica Corazza, Alessandro Pileri
{"title":"OX40-OX40L Axis in Cutaneous T-Cell Lymphomas: Pathogenic, Prognostic, and Potential Therapeutic Perspectives.","authors":"Alba Guglielmo, Alessandro Borghi, Corrado Zengarini, Bianca Maria Piraccini, Monica Corazza, Alessandro Pileri","doi":"10.3390/biom15050715","DOIUrl":"https://doi.org/10.3390/biom15050715","url":null,"abstract":"<p><p>Mycosis fungoides (MF) and Sézary syndrome (SS) are the most prevalent forms of cutaneous T-cell lymphoma (CTCL) and are characterized by the proliferation of CD4<sup>+</sup> T-helper cells. The pathogenesis of CTCLs involves a critical interaction between neoplastic cells and the tumor microenvironment. This interaction is driven not only by cytokines but also by surface proteins that mediate cell-cell contact. One such protein, OX40 (also known as CD134), is a member of the TNF receptor superfamily and serves as an induced costimulatory molecule that facilitates the interaction between T-cells and antigen-presenting cells. In this narrative review, we explore the literature surrounding the OX40-OX40L interaction in CTCLs, highlighting its pathogenic and prognostic significance. Additionally, we compare the expression and function of OX40-OX40L in chronic inflammatory skin diseases, such as atopic dermatitis and psoriasis, with their role in CTCLs. Finally, we provide an overview of the current state of therapeutic research, discussing the potential of targeting the OX40-OX40L axis in CTCL treatment.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-13DOI: 10.3390/biom15050717
Xiao-Xuan Shi, Yu-Ru Liu, Ping Xie
{"title":"Factors Determining Kinesin Motors in a Predominant One-Head-Bound or Two-Heads-Bound State During Its Stepping Cycle.","authors":"Xiao-Xuan Shi, Yu-Ru Liu, Ping Xie","doi":"10.3390/biom15050717","DOIUrl":"https://doi.org/10.3390/biom15050717","url":null,"abstract":"<p><p>At physiological or saturating ATP concentrations, some families of kinesin motors, such as kinesin-1 and kinesin-2, exhibit a predominant two-heads-bound (2HB) state during their stepping cycle on microtubules, while others, such as kinesin-3, exhibit a predominant one-head-bound (1HB) state. An interesting but unclear issue is what factors determine a kinesin motor in the predominant 1HB and 2HB states. Here, on the basis of the general chemomechanical pathway of the kinesin motors, a theory is given on fractions of 1HB and 2HB states. With the theory, the factors affecting a kinesin motor in the predominant 1HB and 2HB states are determined. The results about the effects of ATP concentration, ADP concentration and external load on the fractions of 1HB and 2HB states are presented. Furthermore, the theory is applied to kinesin-1, kinesin-2, kinesin-3, kinesin-5 and kinesin-13 motors, with the theoretical results agreeing well with published experimental data.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-13DOI: 10.3390/biom15050711
Pablo A Iglesias González, Consuelo Mori, Ángel G Valdivieso, Tomás A Santa Coloma
{"title":"Vitamin D and Retinoic Acid Require Protein Kinase C Activity and Reactive Oxygen Species as Opposing Signals Regulating <i>PEIG-1</i>/<i>GPRC5A</i> Expression in Caco-2 and T84 Colon Carcinoma Cells.","authors":"Pablo A Iglesias González, Consuelo Mori, Ángel G Valdivieso, Tomás A Santa Coloma","doi":"10.3390/biom15050711","DOIUrl":"https://doi.org/10.3390/biom15050711","url":null,"abstract":"<p><p><i>PEIG-1/GPRC5A</i> (phorbol ester induced gene-1/G-protein Coupled Receptor Class C Group 5 Member A) was the first identified member of the orphan G protein-coupled receptor family GPRC5. Deregulation of its expression is associated with the development and progression of various types of tumours, particularly colon carcinoma. In this work, we study the effects of vitamin D (VD, cholecalciferol) and retinoic acid (RA) on <i>GPRC5A</i> mRNA expression in the colorectal cancer cell lines Caco-2 and T84. Both VD (10 µM) and all-trans retinoic acid (ATRA, atRA, RA) (10 µM) increased <i>GPRC5A</i> mRNA levels. Protein kinase C (PKC) inhibition with Gö6983 (10 µM) completely abolished the effects of VD and RA on <i>GPRC5A</i> expression. In parallel, VD and RA increased cytosolic and mitochondrial ROS levels (cROS and mtROS). However, the antioxidants NAC (10 mM) and MitoTEMPO (10 µM) raised <i>GPRC5A</i> gene expression levels in the presence of VD or RA, suggesting that elevated ROS may inhibit <i>GPRC5A</i> expression. In conclusion, both VD and RA stimulate <i>GPRC5A</i> expression. The mechanisms involve a common and essential PKC signalling pathway, as Gö6983 inhibited both VD- and RA-induced signalling.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-13DOI: 10.3390/biom15050716
Yanquan Liu, Huanwen Tang
{"title":"CXCR Family and Hematologic Malignancies in the Bone Marrow Microenvironment.","authors":"Yanquan Liu, Huanwen Tang","doi":"10.3390/biom15050716","DOIUrl":"https://doi.org/10.3390/biom15050716","url":null,"abstract":"<p><p>Malignant hematologic diseases, also referred to as hematologic tumors, encompass a series of malignant proliferative disorders of the lymphopoietic system, including leukemia, lymphoma, multiple myeloma, and myeloproliferative neoplasms. The dysregulation of inflammatory factors or chronic inflammatory responses plays an indispensable role in the onset and progression of these tumors. The C-X-C motif chemokine receptor (CXCR) serves as a key mediator of immune-inflammatory responses. Through its specific regulatory mechanisms, CXCR is involved in the transduction and activation of various signaling pathways, thereby mediating the malignant biological characteristics of blood tumor cells, such as uncontrolled proliferation, differentiation, invasion, migration, autophagy, and apoptosis. In the bone marrow microenvironment, CXCR plays a pivotal role. This review systematically analyzes and elucidates the roles and mechanisms of the CXCR family in hematologic malignancies, aiming to provide new insights into the biological mechanisms and clinical significance of these diseases. The CXCR family holds great potential as a molecular marker for both fundamental research and the clinical diagnosis and treatment of hematologic malignancies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-13DOI: 10.3390/biom15050714
Natalia García-Acosta, Rosa Cert, Marta Jordán, Luis Goya, Raquel Mateos, Jose Luis Espartero
{"title":"Hydroxytyrosyl Eicosapentaenoate as a Potential Antioxidant for Omega-3 Fatty Acids: Improved Synthesis and Comparative Evaluation with Other Natural Antioxidants.","authors":"Natalia García-Acosta, Rosa Cert, Marta Jordán, Luis Goya, Raquel Mateos, Jose Luis Espartero","doi":"10.3390/biom15050714","DOIUrl":"https://doi.org/10.3390/biom15050714","url":null,"abstract":"<p><p>Hydroxytyrosol (HT), the primary phenolic compound in virgin olive oil, has notable cardiovascular benefits, particularly in preventing low-density lipoprotein (LDL) oxidation. However, its hydrophilicity limits its solubility and integration into lipid-based formulations. This study aimed to enhance its lipophilicity by synthesizing hydroxytyrosyl eicosapentaenoate (HT-EPA), a derivative of HT and eicosapentaenoic acid (EPA), using a one-step enzymatic catalysis with lipase B from <i>Candida antarctica</i> (CALB). The reaction, performed as a suspension of HT in ethyl eicosapentaenoate (Et-EPA) (1:9 molar ratio) under vacuum, achieved higher yields and shorter reaction times than previously reported, with a purity exceeding 98%, confirmed by <sup>1</sup>H-NMR. For the first time, the antioxidant capacity of HT-EPA in comparison with other natural antioxidants was assessed using the FRAP assay, while its oxidative stability in an omega-3-rich oil matrix was evaluated via the Rancimat method. HT-EPA and hydroxytyrosyl acetate (HT-Ac) displayed antioxidant activity comparable to HT but significantly higher than α-tocopherol, a common food antioxidant. Given the scarcity of effective lipid-soluble antioxidants, HT-EPA represents a promising candidate for omega-3 nutraceuticals, offering enhanced stability and potential health benefits. This study provides a simple, efficient, and scalable strategy for developing functional lipid-based formulations with cardioprotective potential by improving HT solubility while preserving its antioxidant properties.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.","authors":"Shuoyang Hu, Jirun Xu, Weiyan Cui, Haoran Jin, Xiaoyu Wang, Yasen Maimaitiyiming","doi":"10.3390/biom15050702","DOIUrl":"https://doi.org/10.3390/biom15050702","url":null,"abstract":"<p><p>Multiple myeloma (MM) remains an incurable hematologic malignancy due to the inevitable development of drug resistance, particularly in relapsed or refractory cases. Post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, and glycosylation, play pivotal roles in regulating protein function, stability, and interactions, thereby influencing MM pathogenesis and therapeutic resistance. This review comprehensively explores the mechanisms by which dysregulated PTMs contribute to drug resistance in MM, focusing on their impact on key signaling pathways, metabolic reprogramming, and the tumor microenvironment. We highlight how PTMs modulate drug uptake, alter drug targets, and regulate cell survival signals, ultimately promoting resistance to PIs, IMiDs, and other therapeutic agents. Furthermore, we discuss emerging therapeutic strategies targeting PTM-related pathways, which offer promising avenues for overcoming resistance to treatment. By integrating preclinical and clinical insights, this review underscores the potential of PTM-targeted therapies to enhance treatment efficacy and improve patient outcomes in MM.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-05-12DOI: 10.3390/biom15050706
He Wang, Wenchao Cai, Zhiyu Tang, Juanli Fu, Enrico König, Nanwen Zhang, Xiaole Chen, Tianbao Chen, Chris Shaw
{"title":"Discovery and Characterisation of Novel Poly-Histidine-Poly-Glycine Peptides as Matrix Metalloproteinase Inhibitors.","authors":"He Wang, Wenchao Cai, Zhiyu Tang, Juanli Fu, Enrico König, Nanwen Zhang, Xiaole Chen, Tianbao Chen, Chris Shaw","doi":"10.3390/biom15050706","DOIUrl":"https://doi.org/10.3390/biom15050706","url":null,"abstract":"<p><p>For the first time, two poly-histidine-poly-glycine peptides (pHpG-H5 and pHpG-H7) were identified as promising candidates for matrix metalloproteinase inhibitors. cDNAs encoding pHpG-H5 and pHpG-H7 peptides were isolated from the <i>Atheris squamigera</i> cDNA library constructed using oligo(dT)-primed reverse transcription. Deduced sequences of pHpG peptides were systematically organised and utilised as templates for synthesising chemical replicates. All synthetic pHpG peptides exhibited inhibitory effects on human matrix metalloproteinase-1 (MMP-1). Spectroscopic analyses and molecular modelling demonstrated that pHpG peptides disrupt zinc ion coordination within the central catalytic domain of MMP-1, thereby inhibiting its enzymatic activity. As a novel peptide inhibitor of matrix metalloproteinase, pHpG-H7 modulates multiple biological processes, such as cell migration and angiogenesis, suggesting significant therapeutic potential.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}