{"title":"Iberverin Downregulates GPX4 and SLC7A11 to Induce Ferroptotic Cell Death in Hepatocellular Carcinoma Cells.","authors":"Haoying Yang, Bolei Dai, Liangjie Chen, Yingping Li, Xiaorui Jin, Chengchang Gao, Linfen Han, Xueli Bian","doi":"10.3390/biom14111407","DOIUrl":"10.3390/biom14111407","url":null,"abstract":"<p><p>Ferroptosis, a recently elucidated style of regulated cell death, has emerged as a significant area of investigation in cancer biology. Natural active compounds that have anti-cancer effects are promising candidates for cancer prevention. Iberverin, a natural compound derived from <i>Brassica oleracea</i> var. <i>capitata</i>, has been shown to exert anti-tumor activities in some cancers. However, its role in hepatocellular carcinoma (HCC) cells and the molecular mechanisms are still poorly understood. In this study, we proved that iberverin can induce intracellular reactive oxygen species (ROS) generation to inhibit cell proliferation and initiate ferroptotic cell death in HCC cells, which can be eradicated by the ferroptosis inhibitor ferrostatin-1 (Fer-1) or deferoxamine mesylate (DFO) and ROS scavenger (GSH or NAC). Mechanistically, iberverin treatment can simultaneously downregulate <i>SLC7A11</i> mRNA level and degrade GPX4 through the ubiquitination pathway, leading to lipid peroxidation and ferroptotic cell death in HCC cells. Significantly, a low dose of iberverin can remarkably increase the sensitivity of HCC cells to ferroptosis induced by canonical ferroptosis inducers RSL3 and imidazole ketone erastin (IKE). This study uncovers a critical function of iberverin in preventing HCC through ferroptosis and provides a promising strategy for HCC treatment either via iberverin alone or in combination with canonical ferroptosis inducers in the future.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725903","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}
BiomoleculesPub Date : 2024-11-05DOI: 10.3390/biom14111409
Bo Fu, Hong Ma, Xiupeng Huo, Ying Zhu, Di Liu
{"title":"CRISPR Technology Acts as a Dual-Purpose Tool in Pig Breeding: Enhancing Both Agricultural Productivity and Biomedical Applications.","authors":"Bo Fu, Hong Ma, Xiupeng Huo, Ying Zhu, Di Liu","doi":"10.3390/biom14111409","DOIUrl":"10.3390/biom14111409","url":null,"abstract":"<p><p>Pigs have long been integral to human society for their roles in agriculture and medicine. Consequently, there is an urgent need for genetic improvement of pigs to meet human dual needs for medicine and food. In agriculture, gene editing can improve productivity traits, such as growth rate and disease resistance, which could lower farming costs and benefit consumers through enhanced meat quality. In biomedical research, gene-edited pigs offer invaluable resources as disease models and in xenotransplantation, providing organs compatible with human physiology. Currently, with CRISPR technology, especially the CRISPR/Cas9 system emerging as a transformative force in modern genetics, pigs are not only sources of sustenance but also cornerstones of biomedical innovation. This review aims to summarize the applications of CRISPR/Cas9 technology in developing pigs that serve dual roles in agriculture and biomedical applications. Compared to ZFNs and TALENs, the CRISPR/Cas9 system offers several advantages, including higher efficiency, greater specificity, ease of design and implementation, and the capability to target multiple genes simultaneously, significantly streamlining the process of genetic modifications in complex genomes. Therefore, CRISPR technology supports the enhancement of traits beneficial for agricultural productivity and facilitates applications in medicine. Furthermore, we must acknowledge the inherent deficiencies and technical challenges of the CRISPR/Cas9 technology while also anticipating emerging technologies poised to surpass CRISPR/Cas9 as the next milestones in gene editing. We hypothesize that with the continuous advancements in gene editing technologies and successful integration of traits beneficial to both agricultural productivity and medical applications, the goal of developing dual-purpose pigs for both agricultural and medical use can ultimately be achieved.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725608","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}
BiomoleculesPub Date : 2024-11-05DOI: 10.3390/biom14111406
Małgorzata Lorek, Piotr Kamiński, Jędrzej Baszyński, Tadeusz Tadrowski, Edward Jacek Gorzelańczyk, Julia Feit, Natalia Kurhaluk, Alina Woźniak, Halina Tkaczenko
{"title":"Molecular and Environmental Determinants of Addictive Substances.","authors":"Małgorzata Lorek, Piotr Kamiński, Jędrzej Baszyński, Tadeusz Tadrowski, Edward Jacek Gorzelańczyk, Julia Feit, Natalia Kurhaluk, Alina Woźniak, Halina Tkaczenko","doi":"10.3390/biom14111406","DOIUrl":"10.3390/biom14111406","url":null,"abstract":"<p><p>Knowledge about determinants of addiction in people taking addictive substances is poor and needs to be supplemented. The novelty of this paper consists in the analysis of innovative aspects of current research about relationships between determinants of addiction in Polish patients taking addictive substances and rare available data regarding the relationships between these factors from studies from recent years from other environments, mainly in Europe, and on the development of genetic determinants of physiological responses. We try to explain the role of the microelements Mn, Fe, Cu, Co, Zn, Cr, Ni, Tl, Se, Al, B, Mo, V, Sn, Sb, Ag, Sr, and Ba, the toxic metals Cd, Hg, As, and Pb, and the rare earth elements Sc, La, Ce, Pr, Eu, Gd, and Nd as factors that may shape the development of addiction to addictive substances or drugs. The interactions between factors (gene polymorphism, especially <i>ANKK1</i> (<i>TaqI A</i>), <i>ANKK1</i> (<i>Taq1 A-CT</i>), <i>DRD2</i> (<i>TaqI B</i>, <i>DRD2 Taq1 B-GA</i>, <i>DRD2 Taq1 B-AA</i>, <i>DRD2-141C Ins/Del</i>), and <i>OPRM1</i> (<i>A118G</i>)) in patients addicted to addictive substances and consumption of vegetables, consumption of dairy products, exposure to harmful factors, and their relationships with physiological responses, which confirm the importance of internal factors as determinants of addiction, are analyzed, taking into account gender and region. The innovation of this review is to show that the homozygous <i>TT</i> mutant of the <i>ANKK1 TaqI A</i> polymorphism <i>rs 1800497</i> may be a factor in increased risk of opioid dependence. We identify a variation in the functioning of the immune system in addicted patients from different environments as a result of the interaction of polymorphisms.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725060","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}
BiomoleculesPub Date : 2024-11-05DOI: 10.3390/biom14111405
Laura Maria De Plano, Alessandra Saitta, Salvatore Oddo, Antonella Caccamo
{"title":"Navigating Alzheimer's Disease Mouse Models: Age-Related Pathology and Cognitive Deficits.","authors":"Laura Maria De Plano, Alessandra Saitta, Salvatore Oddo, Antonella Caccamo","doi":"10.3390/biom14111405","DOIUrl":"10.3390/biom14111405","url":null,"abstract":"<p><p>Since the mid-1990s, scientists have been generating mouse models of Alzheimer's disease to elucidate key mechanisms underlying the onset and progression of the disease and aid in developing potential therapeutic approaches. The first successful mouse model of Alzheimer's disease was reported in 1995 with the generation of the PDAPP mice, which were obtained by the overexpression of gene coding for the amyloid precursor protein (APP). Since then, scientists have used different approaches to develop other APP overexpression mice, mice overexpressing tau, or a combination of them. More recently, Saito and colleagues generated a mouse model by knocking in mutations associated with familial Alzheimer's disease into the APP gene. In this review, we will describe the most used animal models and provide a practical guide for the disease's age of onset and progression. We believe that this guide will be valuable for the planning and experimental design of studies utilizing these mouse models.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725612","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}
BiomoleculesPub Date : 2024-11-05DOI: 10.3390/biom14111408
Linhui Qin, Fang Tong, Sijie Li, Changhong Ren
{"title":"Beyond Pharmacology: The Biological Mechanisms of Remote Ischemic Conditioning in Cerebrovascular Disease.","authors":"Linhui Qin, Fang Tong, Sijie Li, Changhong Ren","doi":"10.3390/biom14111408","DOIUrl":"10.3390/biom14111408","url":null,"abstract":"<p><p>Cerebrovascular diseases (CVDs), comprising predominantly ischemic stroke and chronic cerebral hypoperfusion (CCH), are a significant threat to global health, often leading to disability and mortality. Remote ischemic conditioning (RIC) has emerged as a promising, non-pharmacological strategy to combat CVDs by leveraging the body's innate defense mechanisms. This review delves into the neuroprotective mechanisms of RIC, categorizing its effects during the acute and chronic phases of stroke recovery. It also explores the synergistic potential of RIC when combined with other therapeutic strategies, such as pharmacological treatments and physical exercise. Additionally, this review discusses the pathways through which peripheral transmission can confer central neuroprotection. This review concludes by addressing the challenges regarding and future directions for RIC, emphasizing the need for standardized protocols, biomarker identification, and expanded clinical trials to fully realize its therapeutic potential.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725908","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}
BiomoleculesPub Date : 2024-11-04DOI: 10.3390/biom14111401
Burkitkan Akbay, Zhannur Omarova, Alexander Trofimov, Bayan Sailike, Orynbassar Karapina, Ferdinand Molnár, Tursonjan Tokay
{"title":"Double-Edge Effects of Leucine on Cancer Cells.","authors":"Burkitkan Akbay, Zhannur Omarova, Alexander Trofimov, Bayan Sailike, Orynbassar Karapina, Ferdinand Molnár, Tursonjan Tokay","doi":"10.3390/biom14111401","DOIUrl":"10.3390/biom14111401","url":null,"abstract":"<p><p>Leucine is an essential amino acid that cannot be produced endogenously in the human body and therefore needs to be obtained from dietary sources. Leucine plays a pivotal role in stimulating muscle protein synthesis, along with isoleucine and valine, as the group of branched-chain amino acids, making them one of the most popular dietary supplements for athletes and gym-goers. The individual effects of leucine, however, have not been fully clarified, as most of the studies so far have focused on the grouped effects of branched-chain amino acids. In recent years, leucine and its metabolites have been shown to stimulate muscle protein synthesis mainly via the mammalian target of the rapamycin complex 1 signaling pathway, thereby improving muscle atrophy in cancer cachexia. Interestingly, cancer research suggests that leucine may have either anti-cancer or pro-tumorigenic effects. In the current manuscript, we aim to review leucine's roles in muscle protein synthesis, tumor suppression, and tumor progression, specifically summarizing the molecular mechanisms of leucine's action. The role of leucine is controversial in hepatocellular carcinoma, whereas its pro-tumorigenic effects have been demonstrated in breast and pancreatic cancers. In summary, leucine being used as nutritional supplement for athletes needs more attention, as its pro-oncogenic effects may have been identified by recent studies. Anti-cancer or pro-tumorigenic effects of leucine in various cancers should be further investigated to achieve clear conclusions.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725604","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}
BiomoleculesPub Date : 2024-11-04DOI: 10.3390/biom14111403
Stelios Psarras
{"title":"The Macrophage-Fibroblast Dipole in the Context of Cardiac Repair and Fibrosis.","authors":"Stelios Psarras","doi":"10.3390/biom14111403","DOIUrl":"10.3390/biom14111403","url":null,"abstract":"<p><p>Stromal and immune cells and their interactions have gained the attention of cardiology researchers and clinicians in recent years as their contribution in cardiac repair is increasingly recognized. The repair process in the heart is a particularly critical constellation of complex molecular and cellular events and interactions that characteristically fail to ensure adequate recovery following injury, insult, or exposure to stress conditions in this regeneration-hostile organ. The tremendous consequence of this pronounced inability to maintain homeostatic states is being translated in numerous ways promoting progress into heart failure, a deadly, irreversible condition requiring organ transplantation. Fibrosis is in fact a repair response eventually promoting cardiac dysfunction and cardiac fibroblasts are the major cellular players in this process, overproducing collagens and other extracellular matrix components when activated. On the other hand, macrophages may differentially affect fibroblasts and cardiac repair depending on their status and subsets. The opposite interaction is also probable. We discuss here the multifaceted aspects and crosstalk of this cell dipole and the opportunities it may offer for beneficial manipulation approaches that will hopefully lead to progress in heart disease interventions.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725951","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":"Research Advances in Adenomyosis-Related Signaling Pathways and Promising Targets.","authors":"Hongyu Zhang, Chaoming Li, Wenyan Li, Wenhu Xin, Tiansheng Qin","doi":"10.3390/biom14111402","DOIUrl":"10.3390/biom14111402","url":null,"abstract":"<p><p>Adenomyosis is a benign gynecological condition characterized by the proliferation of the endometrial stroma and glands into the myometrium, uterine volume enlargement, and peripheral smooth muscle hypertrophy. The typical clinical symptoms include chronic pelvic pain, abnormal uterine bleeding, and subfertility, all of which significantly impact quality of life. There are no effective prevention or treatment strategies for adenomyosis, partly due to a limited understanding of the pathological mechanisms underlying the initiation and progression of the disease. Given that signaling pathways play a crucial role in the development of adenomyosis, a better understanding of these signaling pathways is essential for identifying therapeutic targets and advancing drug development. The occurrence and progression of adenomyosis are closely linked to various underlying pathophysiological mechanisms, including proliferation, migration, invasion, fibrosis, angiogenesis, inflammation, oxidative stress, immune response, and epigenetic changes. This review summarizes the signaling pathways and targets associated with the pathogenesis of adenomyosis, including CXCL/CXCR, NLRP3, NF-κB, TGF-β/smad, VEGF, Hippo/YAP, PI3K/Akt/mTOR, JAK/STAT, and other relevant pathways. In addition, it identifies promising future targets for the development of adenomyosis treatment, such as m6A, GSK3β, sphks, etc.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725774","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}
BiomoleculesPub Date : 2024-11-04DOI: 10.3390/biom14111404
Nabin Giri, Jianlin Cheng
{"title":"Correction: Giri et al. Improving Protein-Ligand Interaction Modeling with cryo-EM Data, Templates, and Deep Learning in 2021 Ligand Model Challenge. <i>Biomolecules</i> 2023, <i>13</i>, 132.","authors":"Nabin Giri, Jianlin Cheng","doi":"10.3390/biom14111404","DOIUrl":"10.3390/biom14111404","url":null,"abstract":"<p><p>There was an error in the original publication [...].</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725595","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}
BiomoleculesPub Date : 2024-11-03DOI: 10.3390/biom14111400
Caroline Frisendahl, Yiqun Tang, Nageswara Rao Boggavarapu, Maire Peters, Parameswaran Grace Lalitkumar, Terhi T Piltonen, Riikka K Arffman, Andres Salumets, Martin Götte, Eberhard Korsching, Kristina Gemzell-Danielsson
{"title":"miR-193b-5p and miR-374b-5p Are Aberrantly Expressed in Endometriosis and Suppress Endometrial Cell Migration In Vitro.","authors":"Caroline Frisendahl, Yiqun Tang, Nageswara Rao Boggavarapu, Maire Peters, Parameswaran Grace Lalitkumar, Terhi T Piltonen, Riikka K Arffman, Andres Salumets, Martin Götte, Eberhard Korsching, Kristina Gemzell-Danielsson","doi":"10.3390/biom14111400","DOIUrl":"10.3390/biom14111400","url":null,"abstract":"<p><p>(1) Background: Endometriosis is a highly prevalent gynecological disease affecting 10% of women of reproductive age worldwide. miRNAs may play a role in endometriosis, though their exact function remains unclear. This study aimed to identify differentially expressed miRNAs in endometriosis and study their functions in the disease. (2) Methods: Endometrial tissue was collected from women with endometriosis (n = 15) and non-endometriosis controls (n = 17). Dysregulated miRNAs were identified through small RNA-sequencing, and their biological significance was explored by target gene prediction and pathway analysis. Selected miRNAs were examined in paired ectopic endometriomas and eutopic endometrium (n = 10) using qRT-PCR. Their roles in cell migration and proliferation were further examined in vitro using functional assays. To identify potential target genes, we performed mRNA sequencing on transfected cells and the endometrioma cohort. (3) Results: We identified 14 dysregulated miRNAs in the eutopic endometrium of women with endometriosis compared to endometrial tissue from women without endometriosis. Pathway analysis indicated enrichment in cell migration and proliferation-associated pathways. Further ex vivo studies of miR-193b-5p and miR-374b-5p showed that both miRNAs were upregulated in endometrioma. Overexpression of these two miRNAs in vitro inhibited cell migration, and mRNA sequencing revealed several migration-related genes that are targeted by these miRNAs. (4) Conclusions: Our study identified two key endometrial miRNAs that may be involved in the pathogenesis of endometriosis by regulating cell migration.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725933","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}