BiomoleculesPub Date : 2025-03-20DOI: 10.3390/biom15030444
James C L Chow
{"title":"Nanomaterial-Based Molecular Imaging in Cancer: Advances in Simulation and AI Integration.","authors":"James C L Chow","doi":"10.3390/biom15030444","DOIUrl":"10.3390/biom15030444","url":null,"abstract":"<p><p>Nanomaterials represent an innovation in cancer imaging by offering enhanced contrast, improved targeting capabilities, and multifunctional imaging modalities. Recent advancements in material engineering have enabled the development of nanoparticles tailored for various imaging techniques, including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and ultrasound (US). These nanoscale agents improve sensitivity and specificity, enabling early cancer detection and precise tumor characterization. Monte Carlo (MC) simulations play a pivotal role in optimizing nanomaterial-based imaging by modeling their interactions with biological tissues, predicting contrast enhancement, and refining dosimetry for radiation-based imaging techniques. These computational methods provide valuable insights into nanoparticle behavior, aiding in the design of more effective imaging agents. Moreover, artificial intelligence (AI) and machine learning (ML) approaches are transforming cancer imaging by enhancing image reconstruction, automating segmentation, and improving diagnostic accuracy. AI-driven models can also optimize MC-based simulations by accelerating data analysis and refining nanoparticle design through predictive modeling. This review explores the latest advancements in nanomaterial-based cancer imaging, highlighting the synergy between nanotechnology, MC simulations, and AI-driven innovations. By integrating these interdisciplinary approaches, future cancer imaging technologies can achieve unprecedented precision, paving the way for more effective diagnostics and personalized treatment strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728082","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 : 2025-03-20DOI: 10.3390/biom15030447
Nuria Pujol Carrión, Maria Ángeles de la Torre-Ruiz
{"title":"Heterologous Expression of Either Human or Soya Bean Ferritins in Budding Yeast Reveals Common Functions Protecting Against Oxidative Agents and Counteracting Double-Strand Break Accumulation.","authors":"Nuria Pujol Carrión, Maria Ángeles de la Torre-Ruiz","doi":"10.3390/biom15030447","DOIUrl":"10.3390/biom15030447","url":null,"abstract":"<p><p>Ferritins are globular proteins that, upon self-assembly in nanocages, are capable of bio-safely storing huge concentrations of bioavailable iron. They are present in most cell types and organisms; one of the exceptions is yeast. Heterologous expression of either human or vegetal ferritins in <i>Saccharomyces cerevisiae</i> revealed new and unknown functions for soya bean ferritins; validated this model by confirming previously characterized functions in human ferritins and also demonstrated that, like human H chain, vegetal H1, and H2 chains also shown a tendency to localize in the nucleus when expressed in an eukaryotic cell model lacking plastids and chloroplasts. Furthermore, when expressed in the system budding yeast, the four ferritins (human H and L and soya bean H1 and H2 chains) present equivalent and relevant functions as protectors against oxidative damage and against the accumulation of double-strand breaks in the DNA. We present evidence demonstrating that these effects are exclusively observed with oxidative agents that operate through the Fenton reaction, such as H<sub>2</sub>O<sub>2</sub>. Here, we also discuss the ferritin requirement for N-glycosylation to exert these functions. We believe that our approach might contribute to extending the knowledge around ferritin function and its consequent relevance to human health.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728237","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 : 2025-03-20DOI: 10.3390/biom15030449
Silvana Aguilar, Daniel Moreira, Ana Laura Pereira Lourenço, Natalia Wilke, Matías A Crosio, Andreanne Vasconcelos, Eder Alves Barbosa, Elizabete C I Bispo, Felipe Saldanha-Araujo, Marcelo H S Ramada, Franco M Escobar, Cristina V Torres, José R S A Leite, Mariela M Marani
{"title":"Enhancing Antimicrobial Peptides from Frog Skin: A Rational Approach.","authors":"Silvana Aguilar, Daniel Moreira, Ana Laura Pereira Lourenço, Natalia Wilke, Matías A Crosio, Andreanne Vasconcelos, Eder Alves Barbosa, Elizabete C I Bispo, Felipe Saldanha-Araujo, Marcelo H S Ramada, Franco M Escobar, Cristina V Torres, José R S A Leite, Mariela M Marani","doi":"10.3390/biom15030449","DOIUrl":"10.3390/biom15030449","url":null,"abstract":"<p><p>Antimicrobial resistance is a global health threat, which has been worsened by the slow development of new antibiotics. The rational design of natural-derived antimicrobial peptides (AMPs) offers a promising alternative for enhancing the efficacy of AMPs and accelerating drug discovery. This paper describes the rational design of improved peptide derivatives starting from hylin-Pul3, a peptide previously isolated from the frog <i>Boana pulchella,</i> by optimizing its hydrophobicity, cationicity, and amphipathicity. In silico screening identified six promising candidates: dHP3-31, dHP3-50, dHP3-50.137, dHP3-50.190, dHP3-84, and dHP3-84.39. These derivatives exhibited enhanced activity against Gram-negative bacteria, emphasizing the role of cationicity and the strategic arginine incorporation. Hemolytic assays revealed the derivatives' improved selectivity, particularly for the derivatives with \"imperfect amphipathicity\". In fibroblast assays, dHP3-84 was well-tolerated, while dHP3-84.39 promoted cell proliferation. Antioxidant assays (ABTS assays) highlighted the Trp-containing derivatives' (dHP3-50.137, dHP3-31) significant activity. The lipid membrane interaction studies showed that hylin-Pul3 disrupts membranes directly, while dHP3-84.39, dHP3-50, and dHP3-50.137 promote vesicle aggregation. Conversely, dHP3-84 did not induce membrane disruption or aggregation, suggesting an intracellular mode of action. Machine learning models were effective in predicting bioactivity, as these predicted AMPs showed enhanced selectivity and potency. Among them, dHP3-84 demonstrated broad-spectrum potential. These findings highlight the value of rational design, in silico screening, and structure-activity studies in optimizing AMPs for therapeutic applications.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728212","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 : 2025-03-20DOI: 10.3390/biom15030450
Shu-Yun Li, Francesco John DeMayo
{"title":"Revolutionizing Implantation Studies: Uterine-Specific Models and Advanced Technologies.","authors":"Shu-Yun Li, Francesco John DeMayo","doi":"10.3390/biom15030450","DOIUrl":"10.3390/biom15030450","url":null,"abstract":"<p><p>Implantation is a complex and tightly regulated process essential for the establishment of pregnancy. It involves dynamic interactions between a receptive uterus and a competent embryo, orchestrated by ovarian hormones such as estrogen and progesterone. These hormones regulate proliferation, differentiation, and gene expression within the three primary uterine tissue types: myometrium, stroma, and epithelium. Advances in genetic manipulation, particularly the Cre/loxP system, have enabled the in vivo investigation of the role of genes in a uterine compartmental and cell type-specific manner, providing valuable insights into uterine biology during pregnancy and disease. The development of endometrial organoids has further revolutionized implantation research. They mimic the native endometrial structure and function, offering a powerful platform for studying hormonal responses, implantation, and maternal-fetal interactions. Combined with omics technologies, these models have uncovered the molecular mechanisms and signaling pathways that regulate implantation. This review provides a comprehensive overview of uterine-specific genetic tools, endometrial organoids, and omics. We explore how these advancements enhance our understanding of implantation biology, uterine receptivity, and decidualization in reproductive research.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728299","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 : 2025-03-20DOI: 10.3390/biom15030454
Yongcheng Su, Qingquan Bai, Wenqing Zhang, Beibei Xu, Tianhui Hu
{"title":"The Role of Long Non-Coding RNAs in Modulating the Immune Microenvironment of Triple-Negative Breast Cancer: Mechanistic Insights and Therapeutic Potential.","authors":"Yongcheng Su, Qingquan Bai, Wenqing Zhang, Beibei Xu, Tianhui Hu","doi":"10.3390/biom15030454","DOIUrl":"10.3390/biom15030454","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive subtype of breast cancer that faces therapeutic challenges due to a shortage of effective targeted therapies. The complex biology of TNBC renders its clinical management fraught with difficulties, especially regarding the immune microenvironment of the tumor. In recent years, long non-coding RNAs (lncRNAs) have been recognized as important gene regulators with key roles in tumor development and microenvironmental regulation. Previous studies have shown that lncRNAs play important roles in the immune microenvironment of TNBC, including the regulation of tumor immune escape and the function of tumor-infiltrating immune cells. However, despite the increasing research on lncRNAs, there are still many unanswered questions, such as their specific mechanism of action and how to effectively utilize them as therapeutic targets. Therefore, the aim of this study was to review the mechanisms of lncRNAs in the TNBC immune microenvironment, explore their regulatory roles in tumor immune escape and immune cell infiltration, and explore their prospects as potential therapeutic targets. By integrating the latest research results, this study aims to provide new ideas and directions for future TNBC treatment.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728331","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 : 2025-03-20DOI: 10.3390/biom15030445
Tao Shen, Wei Wang, Haiyang Wang, Xinyi Zhu, Guoping Zhu
{"title":"Mitochondrial miRNA miR-134-5p Play Oncogenic Role in Clear Cell Renal Cell Carcinoma.","authors":"Tao Shen, Wei Wang, Haiyang Wang, Xinyi Zhu, Guoping Zhu","doi":"10.3390/biom15030445","DOIUrl":"10.3390/biom15030445","url":null,"abstract":"<p><p>Mitochondrial miRNAs (mitomiRs), which are miRNAs that located within mitochondria, have emerged as crucial regulators in a variety of human diseases, including multiple types of cancers. However, the specific role of mitomiRs in clear cell renal cell carcinoma (ccRCC) remains elusive. In this study, we employed a combination of experimental and bioinformatic approaches to uncover the diverse and abundant subcellular distribution of miRNAs within mitochondria in ccRCC. Notably, RNA sequencing after mitochondrial fractionation identified <i>miR-134-5p</i> as a miRNA predominantly detected in the mitochondria of 786O cells, and its expression is significantly upregulated compared to that in 293T cells. Differential expression and survival analyses from TCGA reveal that the upregulation of <i>miR-134-5p</i> is prevalent and closely associated with poor survival outcomes in ccRCC patients. Functionally, exogenous overexpression of <i>miR-134-5p</i> mimics promotes migration in both 786O and Caki-1 cells. Mechanistically, overexpressing the <i>miR-134-5p</i> mimic dramatically downregulates the mRNA levels of <i>CHST6</i>, <i>SFXN2</i>, and <i>GRIK3</i>, whereas the <i>miR-134-5p</i> inhibitor markedly upregulates their expression. Notably, these target mRNAs also predominantly detected in the mitochondria of 786O cells. The downregulated expression signatures of <i>CHST6</i>, <i>SFXN2</i>, and <i>GRIK3</i> are also closely correlated with poor survival outcomes in ccRCC patients. Taken together, our work identifies a novel mitomiR, <i>miR-134-5p</i>, in ccRCC, provides potential targets that could serve as effective biomarkers for ccRCC diagnosis and prognosis, and opens new avenues for understanding the mitomiR-directed regulatory network in ccRCC progression.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727946","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 : 2025-03-20DOI: 10.3390/biom15030446
Dina Šišljagić, Senka Blažetić, Milorad Zjalić, Irena Labak, Vedrana Ivić, Kálmán Ferenc Szűcs, Róbert Gáspár, Eszter Ducza, Sandor G Vari, Andrijana Muller, Marija Heffer
{"title":"Structural and Metabolic Changes in Pregnant Rat Uterine and Adipose Tissue Induced by a High-Fat High-Sugar Diet.","authors":"Dina Šišljagić, Senka Blažetić, Milorad Zjalić, Irena Labak, Vedrana Ivić, Kálmán Ferenc Szűcs, Róbert Gáspár, Eszter Ducza, Sandor G Vari, Andrijana Muller, Marija Heffer","doi":"10.3390/biom15030446","DOIUrl":"10.3390/biom15030446","url":null,"abstract":"<p><p>Pregnancy presents specific metabolic demands, and disruption caused by a high-fat high-sugar diet (HFHSD) have been associated with significant complications, including maternal health risk, fetal developmental issues, and infertility. Obesity-related changes in the uterine tissues may contribute to these challenges. This study analyzed structural changes in the uterus and adipose tissue of pregnant rats on gestation day 22 fed an HFHSD using various staining techniques. Hematoxylin and eosin staining showed morphological changes in the adipose tissue and the uterine structure, including the lumen size and the thickness of the myometrium, endometrium, and perimetrium. The amount of collagen in the uterus was determined by PicroSirius red staining, while PAS-D staining was used to observe glycogen content. Key protein expressions, such as insulin and leptin receptors and UCP1 and UCP3, were analyzed by immunohistochemistry. The HFHSD promoted hypertrophy of visceral and gonadal adipocytes, suggesting metabolic alterations. By the end of pregnancy, a significant reduction in uterine lumen size was observed. Additionally, a decrease in insulin and higher leptin receptor expressions in the myometrium indicated significant physiological alteration. These findings offer insight into how an HFHSD affects uterine structure and function during late pregnancy but should be interpreted within the physiological context of gestation-related metabolic changes. Further research is needed to understand the functional consequences of these alterations on reproductive and metabolic health.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728308","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 : 2025-03-20DOI: 10.3390/biom15030452
Tatevik Sargsyan, Hayarpi M Simonyan, Lala Stepanyan, Avetis Tsaturyan, Caterina Vicidomini, Raffaele Pastore, Germano Guerra, Giovanni N Roviello
{"title":"Neuroprotective Properties of Clove (<i>Syzygium aromaticum</i>): State of the Art and Future Pharmaceutical Applications for Alzheimer's Disease.","authors":"Tatevik Sargsyan, Hayarpi M Simonyan, Lala Stepanyan, Avetis Tsaturyan, Caterina Vicidomini, Raffaele Pastore, Germano Guerra, Giovanni N Roviello","doi":"10.3390/biom15030452","DOIUrl":"10.3390/biom15030452","url":null,"abstract":"<p><p>This study explores the neuropharmacological potential of various molecular and amino acid components derived from <i>Syzygium aromaticum</i> (clove), an aromatic spice with a long history of culinary and medicinal use. Key bioactive compounds such as eugenol, α-humulene, β-caryophyllene, gallic acid, quercetin, and luteolin demonstrate antioxidant, anti-inflammatory, and neuroprotective properties by scavenging free radicals, modulating calcium channels, and reducing neuroinflammation and oxidative stress. Moreover, gallic acid and asiatic acid may exhibit protective effects, including neuronal apoptosis inhibition, while other useful properties of clove phytocompounds include NF-κB pathway inhibition, membrane stabilization, and suppression of pro-inflammatory pathways, possibly in neurons or other relevant cell types, further contributing to neuroprotection and cognitive enhancement. Amino acid analysis revealed essential and non-essential amino acids such as aspartic acid, serine, glutamic acid, glycine, histidine, and arginine in various clove parts (buds, fruits, branches, and leaves). These amino acids play crucial roles in neurotransmitter synthesis, immune modulation, antioxidant defense, and metabolic regulation. Collectively, these bioactive molecules and amino acids contribute to clove's antioxidant, anti-inflammatory, neurotrophic, and neurotransmitter-modulating effects, highlighting its potential as a preventive and therapeutic candidate for neurodegenerative disorders. While preliminary preclinical studies support these neuroprotective properties, further research, including clinical trials, is needed to validate the efficacy and safety of clove-based interventions in neuroprotection.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728265","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 : 2025-03-20DOI: 10.3390/biom15030455
Stefan Kahlert, Constanze Nossol, Marcus Krüger, Sascha Kopp, Daniela Grimm, Simon L Wuest, Hermann-Josef Rothkötter
{"title":"Dynamic Mechanical Load as a Trigger for Growth and Proliferation in Porcine Epithelial Cells.","authors":"Stefan Kahlert, Constanze Nossol, Marcus Krüger, Sascha Kopp, Daniela Grimm, Simon L Wuest, Hermann-Josef Rothkötter","doi":"10.3390/biom15030455","DOIUrl":"10.3390/biom15030455","url":null,"abstract":"<p><p>The impact of gravity is a basic force determining our existence on Earth. Changes in orientation with respect to the gravity vector trigger alternating mechanical forces on organisms, organs, and cells. In the intestines of mammals, epithelial cells are continuously exposed to changed orientations to gravity. In this study, we employed dynamic cultivation systems to mimic the load changes and the resulting mechanical forces. The morphological and functional response of non-cancer-derived porcine epithelial cell lines IPEC-1 and IPEC-J2 was analyzed. We found that dynamic growth conditions affect morphology in the enterocyte model IPEC-1 but not in IPEC-J2. Changes in IPEC-1 were accompanied by modifications of the distribution and structure of the F-actin cytoskeleton rather than the amount. The structure of the apical brush border and the tight junction system seemed to be largely unaffected; however, a robust decrease in transepithelial resistance was found in IPEC-1 and partially in IPEC-J2. We further detected an increase in Ki67, pointing towards accelerated proliferation. In line with this finding, we detected a doubling of cellular mitochondrial respiration, which was not linked to a general increase in the respiratory chain capacity. Dynamic cultivation of confluent epithelial cell layers did not evoke signs of senescence. In summary, we identified the mechanical load cycle as a relevant parameter for the modulation of the morphological structure and physiological behaviour of intestinal epithelial cells.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728256","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":"Inositol and PIP2/PIP3 Ratio: At the Crossroad of the Biodynamic Interface Between Cells and Their Microenvironment.","authors":"Guglielmo Lentini, Alessandro Querqui, Alessandro Giuliani, Roberto Verna, Mariano Bizzarri","doi":"10.3390/biom15030451","DOIUrl":"10.3390/biom15030451","url":null,"abstract":"<p><p>Plasma membrane plays a pivotal role in orchestrating motility and invasive processes, as well as mitosis and genome expression. Indeed, specialized regions of the plasma membrane enriched in phosphoinositides-namely PIP2 and PIP3-can accommodate the requirements of the dynamic interface, which mediates the interplay between cells and their microenvironment. The fine-tuned balance between the two phosphoinositides is instrumental in regulating cytoskeleton organization, motility, ion channel activation, and membrane traffic. The balanced expression of PIP2/PIP3 fulfills these functions by activating pathways through several transporter and receptor proteins. These dynamic interactions modulate the interplay with the extracellular environment by decreasing/increasing their exposure on the cell surface. In this way, lipid structures can rapidly either dismiss or recruit specific proteins, eventually favoring their cooperation with membrane receptors and ion channels. Particularly, exposure of proteins can be managed through the internalization of plasma membrane segments, while receptor signaling can be desensitized by their removal from the cell surface. Notably, the equilibrium between PIP2 and PIP3 is largely dependent on inositol availability, as inositol addition enhances PIP2 content while reducing PIP3 via PI3K inhibition. Pharmacological modulation of PIP2/PIP3 balance promises to be an interesting target in different clinical settings.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728260","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}