Current Issues in Molecular Biology

22 pages, 8254 KiB

Open AccessArticle

Poria cocos Ethanol Extract Restores MK-801-Induced Cytoskeleton Regulation in Neuro2A and IMR-32 Cells and Locomotor Hyperactivity in C57BL/6 Mice by Modulating the Rho Signaling Pathway

by Ya-Ying Chang, Cheng-Wei Lu, Tzu-Yu Lin, I-Shiang Tzeng, Yi-Chyan Chen and Mao-Liang Chen

Curr. Issues Mol. Biol. 2025, 47(5), 312; https://doi.org/10.3390/cimb47050312 (registering DOI) - 28 Apr 2025

Abstract

Poria cocos extract attenuates MK-801-induced hyperactivity via RhoA/ROCK1 pathway modulation in mice. Background/Objectives: Poria cocos (P. cocos), a traditional East Asian medicinal mushroom, serves as a medicine and nutritional supplement, has been used to improve sleep and mood. Its bioactive compounds [...] Read more.

Poria cocos extract attenuates MK-801-induced hyperactivity via RhoA/ROCK1 pathway modulation in mice. Background/Objectives: Poria cocos (P. cocos), a traditional East Asian medicinal mushroom, serves as a medicine and nutritional supplement, has been used to improve sleep and mood. Its bioactive compounds may regulate calcium signaling and Rho family proteins, which are linked to cytoskeletal remodeling and psychiatric symptoms. This study investigated the effects of P. cocos ethanol extract (PCEE) on Rho signaling, cytoskeleton dynamics, and behavior in MK-801-treated cells and mice. Methods: PCEE components were analyzed using HPLC. IMR-32 and Neuro2A cells were treated with MK-801 and PCEE to assess changes in F-actin (via fluorescence staining), cell migration (wound healing and Transwell assays), and Rho signaling proteins (by immunoblotting). In vivo, C57BL/6 mice received MK-801 to induce hyperactivity, followed by PCEE treatment. RhoA/ROCK1 pathway protein levels in the prefrontal cortex were analyzed. Results: PCEE reversed MK-801-induced inhibition of cell migration, F-actin disruption, and dysregulation of Rho-related proteins (RhoGDI1, RhoA, CDC42, Rac1, ROCK1, MLC2, PFN1). In mice, PCEE significantly reduced MK-801-induced hyperactivity and normalized RhoA/ROCK1 signaling in the brain. Conclusion: PCEE modulates cytoskeletal dynamics by regulating RhoA/ROCK1 signaling and attenuates MK-801-induced behavioral and molecular changes, suggesting its therapeutic potential for psychosis with fewer adverse effects. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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16 pages, 1242 KiB

Open AccessArticle

A Novel Application of RNA In Situ Hybridization in the Analysis of Vitamin D Receptor Expression in Psoriatic Skin Tissue Following Etanercept Treatment

by Max Lundgren, Alexandra Kuliszkiewicz, Martin Gillstedt, Azin Jasmin Zanghaneh and Amra Osmancevic

Curr. Issues Mol. Biol. 2025, 47(5), 311; https://doi.org/10.3390/cimb47050311 (registering DOI) - 28 Apr 2025

Abstract

Psoriasis is a chronic inflammatory skin disease marked by abnormal keratinocyte proliferation and immune dysregulation. The vitamin D receptor (VDR) plays a crucial role in regulating skin cell growth and immune responses, but its expression in psoriatic skin and modulation by treatment remain [...] Read more.

Psoriasis is a chronic inflammatory skin disease marked by abnormal keratinocyte proliferation and immune dysregulation. The vitamin D receptor (VDR) plays a crucial role in regulating skin cell growth and immune responses, but its expression in psoriatic skin and modulation by treatment remain unclear. This study aimed to analyze VDR mRNA expression in psoriatic skin tissue before and after etanercept therapy using RNAscope, an RNA in situ hybridization technique that, to the best of our knowledge, has not previously been applied in psoriasis research. Two bio-naïve adult patients with moderate to severe plaque psoriasis received etanercept (50 mg weekly) for 12 weeks. Skin biopsies from lesional and perilesional areas were collected at baseline and post-treatment. VDR expression was assessed in different epidermal layers and the dermis using a semi-quantitative scoring system. In one patient, a statistically significant decrease in VDR expression was observed in the perilesional dermis after treatment (p < 0.001), though this preliminary finding warrants careful interpretation given the very limited cohort size. Both patients exhibited a non-significant trend toward increased VDR expression in the lesional epidermis post-treatment. These preliminary findings suggest that etanercept may modulate VDR expression in psoriatic skin, but individual variability and the small sample size preclude definitive conclusions. The study primarily demonstrates the feasibility of using RNAscope for VDR analysis in patients with psoriasis, an approach that may be novel in this context, and underscores the need for larger investigations to confirm these preliminary findings and further clarify the role of VDR in disease pathogenesis and treatment response. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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16 pages, 750 KiB

Open AccessReview

Harnessing Exosomes: A Brief Overview of Nature’s Nanocarriers and a Glimpse into Their Implications in Pituitary Neuroendocrine Tumors (PitNETs)

by Ligia Gabriela Tataranu

Curr. Issues Mol. Biol. 2025, 47(5), 310; https://doi.org/10.3390/cimb47050310 (registering DOI) - 28 Apr 2025

Abstract

The study of exosomes is currently an area of major interest in the scientific world, especially after the discovery of their function as natural nanocarriers. Their intrinsic features in regulating intricate intracellular pathways have put them in the spotlight in the last decade, [...] Read more.

The study of exosomes is currently an area of major interest in the scientific world, especially after the discovery of their function as natural nanocarriers. Their intrinsic features in regulating intricate intracellular pathways have put them in the spotlight in the last decade, and it has been considered that by harnessing them, the future of cellular communication and therapeutic innovation will experience a breakthrough, leading to pioneering research. However, it has been demonstrated that exosomes have various important roles, from conferring resistance to viral infections of the human placenta to transfer of oncogenic signals between cells, reshaping cellular metabolism, promoting angiogenesis, mediating immune evasion, serving as biomarkers in cancer diagnosis and prognosis, and having implications in the therapeutic management of certain diseases. Besides the general overview of exosomes as nature’s nanocarriers and their functions, this article aims to discuss their implications in PitNETs, especially since there have been many recent studies regarding the clinical benefits of biomolecular medicine. Full article

(This article belongs to the Special Issue Exosomes in Tissue Regeneration and Disease Therapy)

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21 pages, 6859 KiB

Open AccessReview

Targeting SHP2 with Natural Products: Exploring Saponin-Based Allosteric Inhibitors and Their Therapeutic Potential

by Dong-Oh Moon

Curr. Issues Mol. Biol. 2025, 47(5), 309; https://doi.org/10.3390/cimb47050309 (registering DOI) - 27 Apr 2025

Abstract

SHP2, a non-receptor protein tyrosine phosphatase, plays a pivotal role in regulating intracellular signaling pathways, particularly the RAS/MAPK and PI3K/AKT cascades, which are critical for cellular proliferation, differentiation, and survival. Aberrant SHP2 activity, often driven by gain-of-function mutations, is implicated in oncogenesis and [...] Read more.

SHP2, a non-receptor protein tyrosine phosphatase, plays a pivotal role in regulating intracellular signaling pathways, particularly the RAS/MAPK and PI3K/AKT cascades, which are critical for cellular proliferation, differentiation, and survival. Aberrant SHP2 activity, often driven by gain-of-function mutations, is implicated in oncogenesis and drug resistance, making it an attractive therapeutic target. Traditional inhibitors targeting SHP2’s catalytic site face limitations such as poor selectivity and low bioavailability. Recent advancements in allosteric inhibitors, specifically targeting SHP2’s tunnel site, offer improved specificity and pharmacokinetics. Natural products, especially saponins with their unique structural diversity, have emerged as promising candidates for SHP2 inhibition. This review explores the structural and functional dynamics of SHP2, highlights the potential of saponin-based inhibitors, and discusses their mechanisms of action, including their interactions with key residues in the tunnel site. The therapeutic potential of saponins is further emphasized by their ability to overcome the limitations of catalytic inhibitors and their applicability in combination therapies. Future directions include structural optimization to improve pharmacokinetics and the development of innovative strategies such as PROTACs to enhance the clinical utility of saponin-based SHP2 inhibitors. Full article

(This article belongs to the Special Issue Molecular Insights into Food-Derived Natural Products and Their Biological Activities—2nd Edition)

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15 pages, 4748 KiB

Open AccessArticle

Fraxin Alleviates Atherosclerosis by Inhibiting Oxidative Stress and Inflammatory Responses via the TLR4/PI3K/Akt Pathway

by Yaru Wang, Bailing Wei, Mingyang Leng, Jiali He, Yicheng Zhao, Haohao Xia, Haibin Luo and Xue Bai

Curr. Issues Mol. Biol. 2025, 47(5), 308; https://doi.org/10.3390/cimb47050308 (registering DOI) - 27 Apr 2025

Abstract

Fraxin is a bioactive compound derived from Cortex Fraxini. It is known for its diverse biological activities and numerous benefits, including anti-inflammatory, antioxidant, analgesic, antimicrobial, antiviral, and immunomodulatory effects. Despite growing interest in natural compounds for cardiovascular diseases Fraxin’s atheroprotective properties and molecular [...] Read more.

Fraxin is a bioactive compound derived from Cortex Fraxini. It is known for its diverse biological activities and numerous benefits, including anti-inflammatory, antioxidant, analgesic, antimicrobial, antiviral, and immunomodulatory effects. Despite growing interest in natural compounds for cardiovascular diseases Fraxin’s atheroprotective properties and molecular targets have not yet been fully elucidated. To address this gap, our research employed an integrated approach combining network pharmacology, molecular docking simulations, and in vitro biological validation to systematically unravel Fraxin’s therapeutic mechanisms against atherosclerosis (AS). The results showed that 84 potential targets for Fraxin against AS were predicted through public databases, and the key target TLR4 was identified by protein–protein interaction and molecular docking analysis. GO enrichment and KEGG pathway analysis revealed that these potential targets were significantly enriched in the PI3K-Akt and oxidative stress responses pathways. Subsequently conducted in vitro studies validated that Fraxin modulates the TLR4/PI3K/Akt signaling pathway to suppress reactive oxygen species generation and downregulate pro-inflammatory cytokines including Il1b, Il6, and Tnf thereby slowing atherosclerotic disease advancement. This investigation methodically delineates Fraxin’s therapeutic targets and underlying molecular mechanisms in AS management, establishing a scientific foundation for its potential translation into clinical practice. Full article

(This article belongs to the Special Issue Pharmacological Activities and Mechanisms of Action of Natural Products)

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22 pages, 294 KiB

Open AccessReview

CRISPR-Cas9 and Its Bioinformatics Tools: A Systematic Review

by Alicja Jasieniecka and Inês Domingues

Curr. Issues Mol. Biol. 2025, 47(5), 307; https://doi.org/10.3390/cimb47050307 (registering DOI) - 27 Apr 2025

Abstract

CRISPR-Cas9 has revolutionized genetic research with bioinformatics tools essential for tasks like guide RNA design, off-target prediction, and data analysis. This systematic review summarizes the functionality and key features of such tools. Studies published after 2012 were selected through searches in PubMed, Google [...] Read more.

CRISPR-Cas9 has revolutionized genetic research with bioinformatics tools essential for tasks like guide RNA design, off-target prediction, and data analysis. This systematic review summarizes the functionality and key features of such tools. Studies published after 2012 were selected through searches in PubMed, Google Scholar, and other sources, with the final search conducted on 9 November 2024. Seven studies met the criteria, describing around 45 tools, including databases and functional programs. Tools like CRISPResso, CHOPCHOP, and Cas-OFFinder were commonly highlighted, with a major focus on single-guide RNA (sgRNA) design and optimization. Some tools provided specific solutions, while others offered broader functionality, but most lacked experimental validation. Several tools were developed by the authors of the studies, introducing potential bias. Findings highlight a need for integrated platforms that combine functionalities, reducing reliance on fragmented workflows. Current tools often address narrow tasks, complicating their practical application. Future development should focus on comprehensive, multitasking tools to improve accessibility and streamline research processes. Limitations include the descriptive nature of most studies, potential author bias, and challenges in comparing tools objectively. Nonetheless, this review underscores bioinformatics’ critical role in CRISPR research and emphasizes the need for innovative, standardized platforms. This study received no funding and was not registered. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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31 pages, 4089 KiB

Open AccessArticle

A Pilot Investigation of Circulating miRNA Expression in Individuals Exposed to Aluminum and Welding Fumes

by Gözde Öztan, Halim İşsever, Tuğçe İşsever, Fatma Oğuz, Sevgi Canbaz, Canan Küçükgergin and Kazım Yalçın Arga

Curr. Issues Mol. Biol. 2025, 47(5), 306; https://doi.org/10.3390/cimb47050306 (registering DOI) - 26 Apr 2025

Abstract

The objectives of this study comprise the identification of key miRNAs and their target genes associated with severe tolerance in individuals exposed to aluminum and welding fumes, and the elucidation of the underlying regulatory mechanisms. In this study, the levels of seven miRNAs [...] Read more.

The objectives of this study comprise the identification of key miRNAs and their target genes associated with severe tolerance in individuals exposed to aluminum and welding fumes, and the elucidation of the underlying regulatory mechanisms. In this study, the levels of seven miRNAs (hsa-miR-19a-3p, hsa-miR-130b-3p, hsa-miR-25-3p, hsa-miR-363-3p, hsa-miR-92a-3p, hsa-miR-24-3p, and hsa-miR-19b-3p) were analyzed using both hsa-miR-16-5p and RNU6 (U6 snRNA) as reference miRNAs to validate normalization reliability. The qRT-PCR method was used on blood serum samples from 16 workers who were exposed to aluminum, 16 workers who were exposed to welding fumes, and 16 healthy controls who were not exposed to aluminum or welding fumes. We determined heavy metal levels from serum samples of workers exposed to aluminum and welding fumes and control groups using the ICP-OES method. The expression levels of hsa-miR-19a-3p and hsa-miR-19b-3p in aluminum-exposed and control groups were found to be statistically significant (p < 0.05). When workers exposed to welding fumes were compared with the those in the control groups, the expression levels of hsa-miR-19a-3p, hsa-miR-130b-3p, hsa-miR-92a-3p, and hsa-miR-24-3p were observed to be statistically significant (p < 0.05). This study shows that the identification of miRNAs and target genes in different biological functions and pathways plays an important role in understanding the molecular mechanisms of responses to heavy metal toxicity. We share the view that the study will make a significant contribution to the literature in that seven candidate miRNAs can be used as possible biomarkers for exposure to aluminum and welding fumes in humans. Full article

(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)

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17 pages, 10987 KiB

Open AccessArticle

Comprehensive Analysis of Differentially Expressed Profiles of mRNA 5-Methylcytosine Modification in Metabolic Dysfunction-Associated Steatotic Liver Disease

by Yueying Yang, E Wang, Bing Zhou, Yan Lu, Xiaoying Ding and Yao Li

Curr. Issues Mol. Biol. 2025, 47(5), 305; https://doi.org/10.3390/cimb47050305 (registering DOI) - 26 Apr 2025

Abstract

RNA methylation plays a critical role in regulating all aspects of RNA function, which are implicated in the pathogenesis of various human diseases. Recent studies emphasize the role of 5-methylcytosine (m5C), an RNA modification, in key biological functions. Metabolic dysfunction-associated steatotic liver disease [...] Read more.

RNA methylation plays a critical role in regulating all aspects of RNA function, which are implicated in the pathogenesis of various human diseases. Recent studies emphasize the role of 5-methylcytosine (m5C), an RNA modification, in key biological functions. Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading chronic liver condition globally. However, the relationship between m5C methylation and MASLD remains unclear. This study aimed to investigate m5C modification in a mouse model of MASLD. In this research, using RNA transcriptome sequencing (RNA-Seq) and methylated RNA bisulfite sequencing (RNA-BS-Seq) in leptin receptor-deficient mice, we found that genes associated with hypermethylation were primarily linked to lipid metabolism. We identified 156 overlapping and differentially expressed genes (DEGs) that changed at both the mRNA expression level and the m5C modification level. Among them, 72 genes showed elevated expression and m5C modification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these genes were significantly associated with lipid metabolism-related signaling pathways. Our results demonstrate that m5C methylation modifications may play an important role in the development of MASLD. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment, 2nd Edition)

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15 pages, 615 KiB

Open AccessArticle

Genetic Diversity and Breeding System of the Pestiferous Subterranean Termite Reticulitermes flaviceps Across Shaanxi and Sichuan Provinces

by Zahid Khan, Haroon, Yu-Feng Meng and Lian-Xi Xing

Curr. Issues Mol. Biol. 2025, 47(5), 304; https://doi.org/10.3390/cimb47050304 (registering DOI) - 26 Apr 2025

Abstract

The genetic diversity of 22 colonies of the termite Reticulitermes flaviceps was analyzed in Shaanxi and Sichuan provinces. It was found that the genetic diversity in both regions was quite similar. However, the distribution of genetic variations within the colonies was uneven. The [...] Read more.

The genetic diversity of 22 colonies of the termite Reticulitermes flaviceps was analyzed in Shaanxi and Sichuan provinces. It was found that the genetic diversity in both regions was quite similar. However, the distribution of genetic variations within the colonies was uneven. The termite colonies showed moderately high genetic diversity, a positive sign for adaptability and survival. The study also revealed a favorable mix of different genetic types within the colonies, indicating a healthy level of genetic variation. However, there was limited genetic exchange among different colonies, leading to noticeable genetic differences. When looking at the genetic structures, the colonies in Shaanxi were quite similar; those in Sichuan showed more variation, and some Sichuan colonies had identical genetic structures to those in Shaanxi. Regarding breeding systems, the colonies in Shaanxi were mainly extended families, meaning they had multiple generations living together. In contrast, most colonies in Sichuan were simple families consisting of just one generation; this difference might be due to the natural, less disturbed environments in Shaanxi, which support more extensive and complex colonies. On the other hand, the urban environments in Sichuan, with their intricate cement structures, made it difficult for termite colonies to expand. Overall, the study highlights the genetic diversity and breeding strategies of R. flaviceps in different environments, providing insights into their adaptability and survival mechanisms. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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28 pages, 2425 KiB

Open AccessReview

Albumin: A Review of Market Trends, Purification Methods, and Biomedical Innovations

by Muhammad Awais Ashraf, Bei Shen, Muhammad Asif Raza, Zhu Yang, Muhammad Nabeel Amjad, Ghayyas ud Din, Lihuan Yue, Afifa Kousar, Qudsia Kanwal and Yihong Hu

Curr. Issues Mol. Biol. 2025, 47(5), 303; https://doi.org/10.3390/cimb47050303 (registering DOI) - 26 Apr 2025

Abstract

Albumin is the most abundant plasma protein, accounting for approximately 50% of total serum protein in healthy individuals. In recent years, albumin has attracted significant attention due to its biocompatibility, non-toxicity (metabolizing in vivo into harmless degradation products), non-immunogenic properties, ease of purification, [...] Read more.

Albumin is the most abundant plasma protein, accounting for approximately 50% of total serum protein in healthy individuals. In recent years, albumin has attracted significant attention due to its biocompatibility, non-toxicity (metabolizing in vivo into harmless degradation products), non-immunogenic properties, ease of purification, and water solubility. These characteristics render it an ideal candidate for a wide range of biomedical applications. Its uses include drug delivery systems, wound healing, antioxidant therapies, infusion treatments, COVID-19 therapeutics, tissue engineering, and other critical care domains. Consequently, the global demand for albumin has been steadily increasing. The international albumin market was valued at USD 5394.9 million in 2021 and is projected to reach USD 9192 million by 2030, with a compound annual growth rate (CAGR) of 6.1%. Given its diverse applications and rising demand, substantial efforts have been made to ensure a sustainable supply of albumin. This review provides an overview of albumin, along with its novel applications, purification methods, and market trends. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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17 pages, 1402 KiB

Open AccessArticle

A Comparative Study on the Mycelium and Fruiting Body of Meripilus giganteus: Chemical Composition and Biological Activity

by Katarzyna Sułkowska-Ziaja, Mateusz Korczyński, Monika Trepa, Agnieszka Galanty, Jan Lazur, Paweł Kubica, Katarzyna Kała, Paweł Paśko and Bożena Muszyńska

Curr. Issues Mol. Biol. 2025, 47(5), 302; https://doi.org/10.3390/cimb47050302 - 25 Apr 2025

Abstract

Meripilus giganteus (Pers.) P. Karst. is a basidiomycete fungus known for its bioactive properties, including antioxidant, antimicrobial, and cytotoxic effects. Although research has largely focused on fruiting bodies, mycelium obtained through in vitro culture offers a sustainable and potentially scalable source of bioactive [...] Read more.

Meripilus giganteus (Pers.) P. Karst. is a basidiomycete fungus known for its bioactive properties, including antioxidant, antimicrobial, and cytotoxic effects. Although research has largely focused on fruiting bodies, mycelium obtained through in vitro culture offers a sustainable and potentially scalable source of bioactive metabolites. This study aimed to compare the chemical composition and biological activity of extracts from the fruiting bodies and mycelium of M. giganteus. Key compound groups were analyzed using high-performance liquid chromatography (HPLC), and biological activity was assessed through DPPH and ABTS antioxidant assays and MTT-based cytotoxicity testing on human gastrointestinal cancer and normal colon epithelial cell lines. The results revealed distinct metabolite profiles between fungal forms and demonstrated that solvent type strongly influenced extraction efficiency. Cytotoxicity assays indicated moderate activity of both extract types, with some selectivity towards colorectal cancer cell lines. These findings suggest that M. giganteus mycelium may serve as a promising alternative to fruiting bodies for the production of antioxidant and potentially chemopreventive compounds. Further studies are recommended to optimize cultivation and extraction conditions to enhance both metabolite yield and biological activity. Full article

(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)

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18 pages, 1735 KiB

Open AccessReview

Perturbation-Theory Machine Learning for Multi-Target Drug Discovery in Modern Anticancer Research

by Valeria V. Kleandrova, M. Natália D. S. Cordeiro and Alejandro Speck-Planche

Curr. Issues Mol. Biol. 2025, 47(5), 301; https://doi.org/10.3390/cimb47050301 - 25 Apr 2025

Abstract

Cancers constitute a group of biological complex diseases, which are associated with great prevalence and mortality. These medical conditions are very difficult to tackle due to their multi-factorial nature, which includes their ability to evade the immune system and become resistant to current [...] Read more.

Cancers constitute a group of biological complex diseases, which are associated with great prevalence and mortality. These medical conditions are very difficult to tackle due to their multi-factorial nature, which includes their ability to evade the immune system and become resistant to current anticancer agents. There is a pressing need to search for novel anticancer agents with multi-target modes of action and/or multi-cell inhibition versatility, which can translate into more efficacious and safer chemotherapeutic treatments. Computational methods are of paramount importance to accelerate multi-target drug discovery in cancer research but most of them have several disadvantages such as the use of limited structural information through homogeneous datasets of chemicals, the prediction of activity against a single target, and/or lack of interpretability. This mini-review discusses the emergence, development, and application of perturbation-theory machine learning (PTML) as a cutting-edge approach capable of overcoming the aforementioned limitations in the context of multi-target small molecule anticancer discovery. Here, we analyze the most promising investigations on PTML modeling spanning over a decade to enable the discovery of versatile anticancer agents. We highlight the potential of the PTML approach for the modeling of multi-target anticancer activity while envisaging future applications of PTML modeling. Full article

(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)

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15 pages, 5127 KiB

Open AccessArticle

Daphne kiusiana Crude Extract and Its Fraction Enhance Keratinocyte Migration via the ERK/MMP9 Pathway

by Jinu Lee, Seon Min Oh, Hyung Won Ryu and Jeong-Hwa Baek

Curr. Issues Mol. Biol. 2025, 47(5), 300; https://doi.org/10.3390/cimb47050300 - 25 Apr 2025

Abstract

Daphne kiusiana is a naturally occurring plant in East Asia belonging to the Thymelaeaceae family. While its biological properties have been explored, its potential role in wound healing remains largely unknown. This study investigated the effects of Daphne kiusiana extracts on keratinocyte migration [...] Read more.

Daphne kiusiana is a naturally occurring plant in East Asia belonging to the Thymelaeaceae family. While its biological properties have been explored, its potential role in wound healing remains largely unknown. This study investigated the effects of Daphne kiusiana extracts on keratinocyte migration and the underlying mechanisms. The crude extract and its fractions was tested in vitro at various concentrations to evaluate their ability to promote keratinocyte migration, and a cytotoxicity assay was conducted to assess cell viability. The results demonstrated that Daphne kiusiana significantly enhanced keratinocyte migration without inducing notable cytotoxicity at tested concentrations. Mechanistically, this effect was mediated through the modulation of matrix metalloproteinase-9 (MMP-9) via extracellular signal-regulated kinase (ERK) signaling, which plays a crucial role in keratinocyte migration. These findings suggest that Daphne kiusiana may serve as a potential therapeutic agent for enhancing keratinocyte migration in wound healing. However, further investigations, including clinical studies, are necessary to confirm its efficacy and safety. To our knowledge, this is the first study to report the potential of Daphne kiusiana in promoting keratinocyte migration, offering new insights into wound healing therapies. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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16 pages, 452 KiB

Open AccessReview

Selected Medicines That Can Cause Cardiac Arrest with Asystole

by Kamila Czarnecka, Mateusz Jędrzejec, Aleksandra Kukiełczyńska, Jacek Owczarek, Łukasz Olejnik and Paweł Szymański

Curr. Issues Mol. Biol. 2025, 47(5), 299; https://doi.org/10.3390/cimb47050299 - 24 Apr 2025

Abstract

One of the most serious consequences of cardiac arrest is asystole. It can occur in patients suffering from cardio-vascular diseases or during surgery following the use of certain drugs. The aim of this study was to identify the relationship between such use and [...] Read more.

One of the most serious consequences of cardiac arrest is asystole. It can occur in patients suffering from cardio-vascular diseases or during surgery following the use of certain drugs. The aim of this study was to identify the relationship between such use and the occurrence of cardiac arrest or asystole based on a review of literature identified in Science Direct, Web of Science and PubMed. Our findings confirm that a relationship exists between the use of certain drugs and the occurrence of asystole. Most drugs which induce asystole are used in cardiovascular disease, particularly beta-blockers, calcium L-channel blockers and potassium channel blockers. Medicine which can lead to asystole are drugs used, among others, for sedation during surgeries and intended for anesthesia; however, the relationship with asystole is not as clear as for the cardio-vascular drugs. Most patients who experience asystole during surgery after administration of the same drugs had other very serious health problems. Our findings are intended to support medical professionals in anticipating the possibility of asystole after drug administration. Full article

(This article belongs to the Special Issue Unraveling the Molecular Marvels of Heart Repair and Regeneration)

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28 pages, 1378 KiB

Open AccessReview

Endometriosis and Adenomyosis: From Pathogenesis to Follow-Up

by Francesco Giuseppe Martire, Eugenia Costantini, Claudia D’Abate, Giorgia Schettini, Giuseppe Sorrenti, Gabriele Centini, Errico Zupi and Lucia Lazzeri

Curr. Issues Mol. Biol. 2025, 47(5), 298; https://doi.org/10.3390/cimb47050298 - 24 Apr 2025

Abstract

Endometriosis and adenomyosis are chronic, hormone-dependent disorders. Estrogens, in particular, play a pivotal role in the pathophysiology of these conditions. Understanding the disease mechanisms, including local hyperestrogenism and reduced progesterone sensitivity, is crucial for effective management. Early diagnosis is essential for appropriate therapeutic [...] Read more.

Endometriosis and adenomyosis are chronic, hormone-dependent disorders. Estrogens, in particular, play a pivotal role in the pathophysiology of these conditions. Understanding the disease mechanisms, including local hyperestrogenism and reduced progesterone sensitivity, is crucial for effective management. Early diagnosis is essential for appropriate therapeutic intervention, with medical hormonal treatment being the first-line approach. It is important to monitor patients over time and tailor hormone therapy to individual needs in order to optimize treatment adherence. Medical therapy not only enhances patients’ quality of life but also appears to slow disease progression in terms of both extent and severity. This narrative review aims to explore all aspects of endometriosis and adenomyosis, from pathogenesis to clinical symptoms, with particular emphasis on the role of hormones and the use of medical therapies. Full article

(This article belongs to the Section Molecular Medicine)

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20 pages, 2409 KiB

Open AccessReview

The Mechanical Role of YAP/TAZ in the Development of Diabetic Cardiomyopathy

by Jun-Xian Shen, Ling Zhang, Huan-Huan Liu, Zhen-Ye Zhang, Ning Zhao, Jia-Bin Zhou, Ling-Ling Qian and Ru-Xing Wang

Curr. Issues Mol. Biol. 2025, 47(5), 297; https://doi.org/10.3390/cimb47050297 - 23 Apr 2025

Abstract

Diabetic cardiomyopathy (DCM) begins with a subclinical stage featuring cardiac hypertrophy, fibrosis, and disrupted signaling. These changes, especially fibrosis and stiffness, often lead to clinical heart failure. The mechanism involves metabolic dysregulation, oxidative stress, and inflammation, leading to cardiac damage and dysfunction. During [...] Read more.

Diabetic cardiomyopathy (DCM) begins with a subclinical stage featuring cardiac hypertrophy, fibrosis, and disrupted signaling. These changes, especially fibrosis and stiffness, often lead to clinical heart failure. The mechanism involves metabolic dysregulation, oxidative stress, and inflammation, leading to cardiac damage and dysfunction. During the progression of the disease, the myocardium senses surrounding mechanical cues, including extracellular matrix properties, tensile tension, shear stress, and pressure load, which significantly influence the pathological remodeling of the heart through mechanotransduction. At the molecular level, the mechanisms by which mechanical cues are sensed and transduced to mediate myocardial mechanical remodeling in DCM remain unclear. The mechanosensitive transcription factors YAP and TAZ fill this gap. This article reviews the latest findings of how YAP and TAZ perceive a wide range of mechanical cues, from shear stress to extracellular matrix stiffness. We focus on how these cues are relayed through the cytoskeleton to the nucleus, where they trigger downstream gene expression. Here, we review recent progress on the crucial role of YAP and TAZ mechanotransduction in the pathological changes observed in DCM, including myocardial fibrosis, hypertrophy, inflammation, mitochondrial dysfunction, and cell death. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

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16 pages, 3010 KiB

Open AccessArticle

Laryngeal Squamous Cell Carcinoma Is Characterized by a Stronger Expression of Nectin-4 Compared to Nectin-2

by Matej Maršić, Nives Jonjić, Maja Gligora Marković, Svjetlana Janković, Marko Velepič, Ilinko Vrebac, Lara Batičić and Tamara Braut

Curr. Issues Mol. Biol. 2025, 47(5), 296; https://doi.org/10.3390/cimb47050296 - 23 Apr 2025

Abstract

Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on [...] Read more.

Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on tissue microarray (TMA) samples derived from 31 patients who underwent total laryngectomy. The findings revealed heterogenous expression of both Nectin-2 and Nectin-4 in tumor cells and surrounding stroma, with Nectin-4 expression being significantly higher than Nectin-2 expression. Specifically, 74% of cases showed weak cytoplasmic staining for Nectin-2, while 41.93% exhibited strong cytoplasmic staining for Nectin-4. Both Nectin-2 and Nectin-4 expressions were more pronounced at the invasive tumor margins. Although no significant differences in Nectin-4 expression were observed across tumor grades (W = 83.500; z = −0.463; p = 0.658), differences in expression patterns were noted. Well-differentiated tumors (Grade 1), 80.65% of cases, showed predominantly membranous Nectin-4 staining, including in squamous epithelial cells of the mucosal surface. Conversely, in less-differentiated tumors (Grade 2 and 3), a shift toward cytoplasmic staining was evident. Specifically, 74.19% of Grade 2 tumors and 100% of Grade 3 tumors showed a predominant cytoplasmic localization of Nectin-4. This transition from membranous to cytoplasmic localization was also evident in the progression from normal superficial epithelium to malignant tissue. These observations suggest that alterations in the expression and subcellular localization of Nectin-4 may be associated with carcinogenesis and could serve as potential markers for the assessment of precancerous lesions and the aggressiveness of laryngeal tumors. Full article

(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)

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14 pages, 2650 KiB

Open AccessReview

Liposomes as Imaging Agents of Inflammation and Oxidative Stress in Bone Implants

by Delia Danila, Patricia S. Pardo, R. Devesh Kumar Misra and Aladin M. Boriek

Curr. Issues Mol. Biol. 2025, 47(5), 295; https://doi.org/10.3390/cimb47050295 - 22 Apr 2025

Abstract

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in [...] Read more.

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in inflammation, such as macrophages, and accumulate at inflammation sites when injected. Additionally, liposomes can be designed to respond to oxidative stress, which is often associated with bone implant complications. By detecting areas of stress, liposomes provide valuable information about implant health. However, challenges such as rapid clearance from the body, precise targeting, immune reactions, and high production costs must be addressed. Research is ongoing to improve the design and functionality of liposomes. They can potentially monitor bone implants as non-invasive imaging agents, enabling early detection of complications and timely interventions. This approach can enhance patient outcomes and extend the longevity of implants, making it a promising strategy for better patient care and implant success. Full article

(This article belongs to the Special Issue Molecular Research on Free Radicals and Oxidative Stress)

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14 pages, 8775 KiB

Open AccessArticle

Enhanced Bioactivity of Fermented Aralia cordata Extract for Glucose and Immune Modulation

by Heejong Shin, Hwapyung Kim, Gwangpyung Kim, Yikyoung Kim and Boyong Kim

Curr. Issues Mol. Biol. 2025, 47(4), 294; https://doi.org/10.3390/cimb47040294 - 21 Apr 2025

Abstract

Excessive glucose absorption is a major contributing factor of metabolic disorders that necessitates effective therapeutic strategies. This study investigates the potential of fermented Aralia cordata extract (FACE) in regulating glucose transport and immune responses under high-glucose stress conditions. Caco-2 intestinal cells and L [...] Read more.

Excessive glucose absorption is a major contributing factor of metabolic disorders that necessitates effective therapeutic strategies. This study investigates the potential of fermented Aralia cordata extract (FACE) in regulating glucose transport and immune responses under high-glucose stress conditions. Caco-2 intestinal cells and L cells were treated with FACE to determine effects on key glucose-regulating proteins and cytokines. FACE treatment inhibited the expression of glucose transporters SGLT1 and GLUT2 while promoting GLP-1 secretion. This effect was associated with HDAC and somatostatin suppression, along with AMPK-γ upregulation. Notably, FACE inhibited DPP-4 expression, further enhancing GLP-1 stability and function. Immunomodulatory effects also occurred, specifically FACE promotion of T lymphocyte differentiation, with a stronger influence on Th2 cell development. Additionally, FACE increased the secretion of essential molecules for immune balance and inflammation control, including antimicrobial peptides LL-37 and defensin, along with cytokines IL-4 and IL-13. These findings suggest that FACE exerts dual effects of improving glucose regulation and modulating immune responses, highlighting its potential as a novel bioactive material for managing metabolic disorders and enhancing intestinal immunity. Further research is warranted to explore its clinical applicability in therapeutic formulations. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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