Current Issues in Molecular Biology

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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Curr. Issues Mol. Biol., Volume 47, Issue 5 (May 2025) – 8 articles

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