International Journal of Molecular Sciences

25 pages, 773 KB

Open AccessReview

Self-Guided Molecular Simulation Methods

by Xiongwu Wu and Bernard R. Brooks

Int. J. Mol. Sci. 2025, 26(21), 10410; https://doi.org/10.3390/ijms262110410 (registering DOI) - 26 Oct 2025

This work reviews self-guided (SG) molecular simulation methods and illustrates the characteristics and applications of these methods through several example simulations. The main characteristic of SG methods is that past motion in simulations is used to guide future motion. Two forms of these [...] Read more.

This work reviews self-guided (SG) molecular simulation methods and illustrates the characteristics and applications of these methods through several example simulations. The main characteristic of SG methods is that past motion in simulations is used to guide future motion. Two forms of these methods are self-guided molecular dynamics (SGMD) and self-guided Langevin dynamics (SGLD). SG methods achieve an enhanced conformational search through promoting low-frequency motion. A simple local averaging scheme is used to extract low-frequency properties from past simulation trajectories to promote low-frequency motion, which significantly enhances conformational search efficiency with little overhead in computing cost. Based on a generalized Langevin equation (GLE), an SGLD-GLE simulation method is developed, which has enhanced conformational searching ability and at the same time can vigorously sample the canonical ensemble. A reformulation of the SG methods leads to a quantitative relation between the guiding parameters and the conformational distribution, which allows the SG methods to be combined with the replica exchange scheme to perform replica-exchanging self-guided simulations (RXSGMD/RXSGLD). RXSGMD/RXSGLD are much more efficient than temperature-based replica exchange methods, especially for large systems. Full article

(This article belongs to the Special Issue Advances in Biomathematics, Computational Biology, and Bioengineering)

21 pages, 3738 KB

Open AccessArticle

Novel Spinel Li–Cr Nano-Ferrites: Structure, Morphology, and Electrical/Dielectric Properties

by Mukhametkali Mataev, Altynai Madiyarova, Moldir Abdraimova, Marzhan Nurbekova, Karima Seibekova, Zhanar Tursyn, Assel Kezdykbayeva, Krishnamoorthy Ramachandran and Bahadir Keskin

Int. J. Mol. Sci. 2025, 26(21), 10409; https://doi.org/10.3390/ijms262110409 (registering DOI) - 26 Oct 2025

Abstract

This article reports on the synthesis and physicochemical characterization of a novel complex ferrite material, LiCr₃.₄Fe₁.₆O₈, prepared via the sol-gel method. X-ray diffraction (XRD) analysis confirmed that the synthesized compound is a single-phase [...] Read more.

This article reports on the synthesis and physicochemical characterization of a novel complex ferrite material, LiCr₃.₄Fe₁.₆O₈, prepared via the sol-gel method. X-ray diffraction (XRD) analysis confirmed that the synthesized compound is a single-phase material with a spinel-type structure and cubic symmetry. Raman spectroscopy was employed to investigate the vibrational modes, and the observed peaks corresponding to Fe–O and Cr–O bonds further validated the spinel-like structure of the compound. The microstructure and elemental composition were examined using scanning electron microscopy (SEM). Multiple regions of the LiCr₃.₄Fe₁.₆O₈ crystals were analyzed, revealing a homogeneous phase and providing detailed insight into the morphology and chemical composition of the surface. The synthesized ferrite particles exhibited relatively large dimensions, with sizes measured at approximately 5, 30, 100, and 200 μm. The dielectric behavior was studied to assess the material’s response to an external electric field, demonstrating its capacity for electric charge polarization. Both capacitance and electrical conductivity were found to increase with rising temperature. Electrophysical measurements were conducted using the LCR-800 system over a temperature range of 293–483 K and at frequencies of 1.5 kHz and 10 kHz. An increase in frequency to 10 kHz resulted in a decrease in the dielectric constant (ε) across the entire temperature range. Full article

(This article belongs to the Section Materials Science)

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27 pages, 831 KB

Open AccessReview

Infrapatellar Fat Pad in Knee Osteoarthritis: A Comprehensive Review of Pathophysiology and Targeted Therapeutic Strategies

by Ilenia Mallia, Antonella Fioravanti and Serena Guiducci

Int. J. Mol. Sci. 2025, 26(21), 10408; https://doi.org/10.3390/ijms262110408 (registering DOI) - 26 Oct 2025

Abstract

Osteoarthritis (OA) is the most common joint disorder globally, affecting approximately 595 million individuals and representing the first cause of chronic pain and disability. Recently, the infrapatellar fat pad (IFP), an intracapsular adipose tissue in the human knee joint, was recognized as an [...] Read more.

Osteoarthritis (OA) is the most common joint disorder globally, affecting approximately 595 million individuals and representing the first cause of chronic pain and disability. Recently, the infrapatellar fat pad (IFP), an intracapsular adipose tissue in the human knee joint, was recognized as an active and metabolically significant contributor to the pathophysiology of OA through the release of pro-inflammatory cytokines, adipokines, and growth factors that sustain inflammatory response, fibrotic remodeling, and neurogenic pain. The present review provides an overview of the pathophysiological significance of the IFP in OA and current and promising therapeutic strategies targeting this adipose structure. We summarize the available preclinical and translational evidence on conservative therapies, minimally invasive interventions, and surgical options as well as IFP-derived mesenchymal stromal cells as a potential cell source for cartilage repair. Overall, preclinical research indicates that the modulation of IFP inflammation and fibrosis could alleviate pain and delay the progression of the disease. The superficial location and its central role in the pathogenesis of OA make the IFP a promising therapeutic target in knee OA (KOA). Full article

(This article belongs to the Special Issue Highlights in Pathophysiology and Treatment of Osteoarthritis)

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21 pages, 732 KB

Open AccessReview

Thrombosis and Anemia in Pediatric Inflammatory Bowel Disease: Pathophysiology, Clinical Impact and Future Directions

by Dragos-Florin Tesoi, Monica Hancianu, Laura Mihaela Trandafir, Manuela Ciocoiu, Maria Cristina Vladeanu, Larisa-Ioana Barbosu, Laura Bozomitu, Otilia Elena Frasinariu, Iris Bararu-Bojan and Oana-Viola Badulescu

Int. J. Mol. Sci. 2025, 26(21), 10407; https://doi.org/10.3390/ijms262110407 (registering DOI) - 26 Oct 2025

Abstract

Pediatric inflammatory bowel disease (PIBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is associated with inflammation that extends beyond the gastrointestinal tract. Among the most significant extraintestinal complications are anemia and thrombosis, both of which can impact disease severity, quality of life, [...] Read more.

Pediatric inflammatory bowel disease (PIBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is associated with inflammation that extends beyond the gastrointestinal tract. Among the most significant extraintestinal complications are anemia and thrombosis, both of which can impact disease severity, quality of life, and long-term outcomes. This review aims to explore the intertwined pathophysiology of anemia and thrombosis, clinical implications of these two complications, and management strategies for anemia and thrombosis in PIBD. Anemia is the most common systemic complication in PIBD, with multifactorial etiologies, including iron deficiency, chronic inflammation, and nutritional deficiencies. Despite its high prevalence, it remains underdiagnosed and undertreated. Thrombosis, although less frequent, poses significant risk, particularly during disease flares, hospitalizations, and in the presence of central venous catheters or corticosteroid therapy. The proinflammatory and hypercoagulable state in inflammatory bowel disease (IBD) increases thrombotic risk, necessitating early identification and, in high-risk cases, consideration of thromboprophylaxis. Anemia and thrombosis represent significant yet often overlooked complications in PIBD. Proactive screening, individualized risk stratification, and integrated management approaches are critical to improving outcomes. Further pediatric-specific research is needed to develop tailored prevention and treatment strategies. Full article

(This article belongs to the Special Issue New Advances in Thrombosis: 3rd Edition)

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15 pages, 693 KB

Open AccessReview

Anticancer Potential of Whey Proteins—A Systematic Review of Bioactivity and Functional Mechanisms

by Selin Elmas, Meliha Fındık, Ramazan Kıyak, Gökhan Taşkın, Daniela Cîrțînă, Rodica Dîrnu, Natalia Guță, Roxana-Maria Mecu and Monica-Delia Bîcă

Int. J. Mol. Sci. 2025, 26(21), 10406; https://doi.org/10.3390/ijms262110406 (registering DOI) - 26 Oct 2025

Abstract

Cancer remains a primary global health concern, with treatment-related side effects and malnutrition posing significant challenges to patient care and recovery. In recent years, there has been growing interest in the therapeutic potential of functional food components, especially whey proteins (WPs), due to [...] Read more.

Cancer remains a primary global health concern, with treatment-related side effects and malnutrition posing significant challenges to patient care and recovery. In recent years, there has been growing interest in the therapeutic potential of functional food components, especially whey proteins (WPs), due to their notable antioxidant, immunomodulatory, and anticancer properties. This systematic review explores the effects of WPs across various cancer types and assesses their value as supportive nutritional agents. A thorough literature search was conducted in PubMed, Scopus, and Web of Science databases, identifying 24 relevant studies published between 2000 and 2024. The selection process followed PRISMA guidelines. The evidence, drawn from both laboratory and clinical research, suggests that WPs may exert anticancer effects by inhibiting tumor cell growth, promoting apoptosis, enhancing antioxidant defenses, modulating immune activity, and influencing signaling pathways such as the PI3K/Akt, mTOR, and Wnt/β-catenin pathways. Colorectal, breast, and liver cancers emerged as the most extensively studied types. Additionally, the form of WP used—whether concentrate, isolate, or hydrolysate—appeared to influence both biological activity and clinical outcomes. Clinical findings suggest that WP supplementation may support nutritional status, mitigate the adverse effects of chemotherapy, and enhance the quality of life in cancer patients. While the preclinical data are compelling, further high-quality randomized controlled trials are needed to confirm these benefits and determine optimal use in clinical practice. This review highlights WPs as promising, well-tolerated nutritional agents with potential to enhance current cancer care strategies. Full article

(This article belongs to the Section Molecular Biology)

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21 pages, 6097 KB

Open AccessArticle

The Role of Mast Cells in Healing Purulent Wounds Using a Drug from the Polyhexamethylene Guanidine Group with the Antiseptic Polyhexanide: An Ultrastructural Study

by Irina Chekmareva, Atim Emaimo John, Andrey Kostin, Alexander Alekhnovich, Artem Volodkin, Ilya Klabukov, Denis Baranovskii, Viktoria Shishkina, Igor Buchwalow, Markus Tiemann and Dmitrii Atiakshin

Int. J. Mol. Sci. 2025, 26(21), 10405; https://doi.org/10.3390/ijms262110405 (registering DOI) - 26 Oct 2025

Abstract

Wound healing is a delicately regulated pathophysiological process based on molecular, cellular, and tissue interactions. Mast cells (MCs) are involved in the reparative process in all phases of wound healing, which indicates their general significance in reparative processes. The structural and functional changes [...] Read more.

Wound healing is a delicately regulated pathophysiological process based on molecular, cellular, and tissue interactions. Mast cells (MCs) are involved in the reparative process in all phases of wound healing, which indicates their general significance in reparative processes. The structural and functional changes in the MCs during the healing process correspond to the phase of the wound process and determine its course. In the inflammatory phase, rapid whole-granular degranulation of MCs with the secretion of biologically active proinflammatory substances that have a stimulating effect on inflammatory cells prevailed. In the proliferation phase, the maximum number of MCs per unit area of wound tissue and the maximum degranulation index were noted. In the phase of granulated tissue remodeling, the amount and functional activity of MCs sharply decrease, which contributes to the completion of the healing process with the formation of a fully fledged normotrophic scar. The gradual degranulation of MCs was characteristic of the proliferation and remodeling phases. The treatment of purulent wounds with a drug from the polyhexamethylene guanidine group with the antiseptic polyhexanide 0.1% contributed to a temporary shift in the phases of the wound process while maintaining its general patterns, while the activation of the process occurred at an earlier time than in the control group of animals without local treatment. The results obtained showed that the use of a drug from the polyhexamethylene guanidine group with the antiseptic polyhexanide 0.1% for the treatment of purulent wounds quickly stops the inflammatory response and creates conditions for the development of the reparative abilities of granulation tissue cells, and primarily, mast cells. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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14 pages, 838 KB

Open AccessArticle

Long-Term Effects of Semaglutide and Sitagliptin on Circulating IGFBP-1, IGFBP-3 and IGFBP-rp1: Results from a One-Year Study in Type 2 Diabetes

by Eszter Dániel, Ferenc Sztanek, Sára Csiha, Balázs Ratku, Sándor Somodi, György Paragh, Mariann Harangi and Hajnalka Lőrincz

Int. J. Mol. Sci. 2025, 26(21), 10404; https://doi.org/10.3390/ijms262110404 (registering DOI) - 26 Oct 2025

Abstract

The role of insulin-like growth factor-binding proteins (IGFBPs) in the regulation of carbohydrate metabolism and the development of complications is well established; however, the impact of the glucagon-like peptide-1 receptor agonist semaglutide on IGFBPs has not been previously investigated. We aimed to examine [...] Read more.

The role of insulin-like growth factor-binding proteins (IGFBPs) in the regulation of carbohydrate metabolism and the development of complications is well established; however, the impact of the glucagon-like peptide-1 receptor agonist semaglutide on IGFBPs has not been previously investigated. We aimed to examine the effects of semaglutide and dipeptidyl peptidase-4 inhibitor sitagliptin therapy on serum levels of IGFBP-1, IGFBP-3, and IGFBP-rp1, and to analyze their associations with anthropometric variables and markers of carbohydrate and lipid metabolism. In this prospective study, we enrolled 34 patients with type 2 diabetes mellitus (T2DM) on metformin monotherapy and 31 age-, sex- and BMI-matched controls. Among the patients, 18 received semaglutide, and 16 were treated with sitagliptin. Anthropometric and laboratory assessments were performed at baseline, 26 and 52 weeks. IGFBP levels were measured using ELISA. Both semaglutide and sitagliptin treatment significantly increased IGFBP-1 levels. IGFBP-3 levels were significantly decreased following sitagliptin therapy. No significant change in IGFBP-rp1 levels was observed with either treatment. Based on multiple regression analysis, the best predictors of IGFBP-1 were insulin and hsCRP, while the best predictor of IGFBP-3 was LDL-C level. Our findings suggest that semaglutide and sitagliptin may exert favorable effects on the GH/IGF-1 axis, potentially contributing to their beneficial metabolic outcomes in patients with T2DM. Full article

(This article belongs to the Collection Feature Paper Collection in Molecular Endocrinology and Metabolism)

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25 pages, 6891 KB

Open AccessArticle

Chemical Modification of Chitosan with Bioactive Molecules: A Sustainable Approach for Advanced Film Development

by Carolina Muñoz-Núñez, Nuria Gómez-Fernández, Alexandra Muñoz-Bonilla and Marta Fernández-García

Int. J. Mol. Sci. 2025, 26(21), 10403; https://doi.org/10.3390/ijms262110403 (registering DOI) - 26 Oct 2025

Abstract

This study presents the synthesis of a new chitosan (CS) derivative incorporating eugenol (EU), a natural compound known for its strong antioxidant properties, with the aim of comparing its properties to those of the previously described thiazolium-chitosan derivative (CS-MTBAQ), employed as antimicrobial component. [...] Read more.

This study presents the synthesis of a new chitosan (CS) derivative incorporating eugenol (EU), a natural compound known for its strong antioxidant properties, with the aim of comparing its properties to those of the previously described thiazolium-chitosan derivative (CS-MTBAQ), employed as antimicrobial component. The functionalization was achieved through a thiol-ene reaction, enabling the covalent bonding of EU and thiol modified chitosan (CS-SH). After detailed characterization of the resulting derivative (CS-SH-EU), a comparative analysis of its antioxidant activities was conducted, revealing that CS-SH-EU films exhibited 25% higher antioxidant efficiency compared to those with CS modified with MTBAQ. Both derivatives were incorporated into chitosan-based films at 10 wt%, which were further reinforced with chitin nanowhiskers at two concentrations, 1 and 5 wt%. The antioxidant, mechanical and structural properties of these films were extensively evaluated as well as the yellowness index and water vapor transmission. The inclusion of these derivatives containing eugenol and thiazolium groups and the chitin nanowhiskers enhanced the mechanical performance, water barrier properties, and antioxidant activity maintained the visual appearance. The formulation applied as coating on strawberries was able to extend their self-life by creating an effective barrier. The findings evidence that the obtained films present a promising alternative for developing active packaging materials, combining enhanced antioxidant efficiency with excellent mechanical and biodegradable properties. Full article

(This article belongs to the Special Issue Functional Polymeric Materials: From Synthesis to Applications: 2nd Edition)

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42 pages, 893 KB

Open AccessReview

miRNAs, lncRNAs, circRNAs and piRNAs in Nonalcoholic Fatty Liver Disease: Past, Present and Future

by Roxana Liana Lucaciu, Olga Hilda Orasan, Adriana Corina Hangan, Mihalea Iancu, Angela Cozma, Sorina Cezara Coste, Sidonia Gog-Bogdan, Sevastre Bogdan and Lucia Maria Procopciuc

Int. J. Mol. Sci. 2025, 26(21), 10402; https://doi.org/10.3390/ijms262110402 (registering DOI) - 26 Oct 2025

Abstract

Nowadays, nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disorder worldwide. From the clinical point of view, it evolves from steatosis to nonalcoholic steatohepatitis, which can lead to cirrhosis and finally to hepatocellular carcinoma. The mechanisms involved in [...] Read more.

Nowadays, nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disorder worldwide. From the clinical point of view, it evolves from steatosis to nonalcoholic steatohepatitis, which can lead to cirrhosis and finally to hepatocellular carcinoma. The mechanisms involved in its progression to more pathological stages and NAFLD pathogenesis are not completely understood. The research concerning NAFLD has become urgent and important because the age of NAFLD diagnosis is progressively decreasing, and its relationship with cancer risk is already well known. Because NAFLD ultimately leads to disability and imposes a major socioeconomic burden, timely diagnosis and effective treatment of NAFLD is particularly important. In the development of NAFLD, noncoding RNAs (ncRNAs) represented by microRNAs, long noncoding RNAs, circular RNAs, and piRNAs are epigenetic factors that play important regulatory roles. In the current review, we present updated information regarding the role of miRNAs, lncRNAs, circRNAs, and piRNAs, aiming to develop a good understanding of their regulatory functions in hepatic metabolism and concerning their potential use as biomarkers for early NAFLD/NASH diagnosis and as therapeutic targets. Full article

(This article belongs to the Special Issue Metabolic Syndrome: New Insights in Pathogenesis, Diagnosis, Prevention, and Management)

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28 pages, 546 KB

Open AccessSystematic Review

Basophil Activation Test (BAT) for Diagnosing LTP Food Allergy: Where Do We Stand Now? A Systematic Review

by Bernadetta Kosztulska, Magdalena Grześk-Kaczyńska, Magdalena Rydzyńska, Zbigniew Bartuzi and Natalia Ukleja-Sokołowska

Int. J. Mol. Sci. 2025, 26(21), 10401; https://doi.org/10.3390/ijms262110401 (registering DOI) - 26 Oct 2025

Abstract

LTP allergy and its accurate diagnosis remain a challenge in modern allergology. Patients sensitized to lipid transfer proteins (LTPs) present a wide range of symptoms, from mild manifestations—such as oral allergy syndrome, urticaria, and angioedema—to severe systemic reactions, including anaphylaxis. Oral food challenges [...] Read more.

LTP allergy and its accurate diagnosis remain a challenge in modern allergology. Patients sensitized to lipid transfer proteins (LTPs) present a wide range of symptoms, from mild manifestations—such as oral allergy syndrome, urticaria, and angioedema—to severe systemic reactions, including anaphylaxis. Oral food challenges (OFCs), the gold standard in food allergy diagnostics, are problematic in this group of patients due to the high risk of life-threatening reactions during the procedure. The basophil activation test (BAT), a functional assay based on flow cytometry, is a promising diagnostic tool that may benefit many food-allergic patients by reducing the need for OFCs. In 2023, BAT was incorporated into selected diagnostic pathways for food sensitization in the guidelines issued by the European Academy of Allergy and Clinical Immunology (EAACI). While many studies have investigated BAT in the context of peanut allergy, evidence regarding its application in LTP allergy remains limited. In this systematic review, we analyzed the currently available studies on the use of BAT in the diagnosis of LTP sensitization and evaluated its potential to supplement or even replace OFCs in specific clinical scenarios. Full article

(This article belongs to the Special Issue Food Allergy: Molecular Mechanisms, Clinical Challenges, and Future Directions)

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21 pages, 832 KB

Open AccessReview

The Managed Acquisition of Chemoresistance as an Informative Tool for Tumor Research

by Tatyana A. Grigoreva, Daria N. Kindt, Aleksandra V. Sagaidak, Angelina A. Romanova and Vyacheslav G. Tribulovich

Int. J. Mol. Sci. 2025, 26(21), 10400; https://doi.org/10.3390/ijms262110400 (registering DOI) - 26 Oct 2025

Abstract

The problem of acquiring chemoresistance by tumor cells is a growing concern for researchers as the effectiveness of diagnosis and treatment of primary tumors increases. To study the mechanisms of resistance, as well as to evaluate the effectiveness of new drugs, it is [...] Read more.

The problem of acquiring chemoresistance by tumor cells is a growing concern for researchers as the effectiveness of diagnosis and treatment of primary tumors increases. To study the mechanisms of resistance, as well as to evaluate the effectiveness of new drugs, it is necessary to use adequate cell models. The review presents modern methods for obtaining chemoresistant cell lines used by researchers in such studies. It examines the most common cytostatics and targeted drugs, such as cisplatin, oxaliplatin, paclitaxel, doxorubicin, 5-fluorouracil, gemcitabine, gefitinib, bortezomib, erlotinib, and the monoclonal antibody cetuximab. Particular attention is paid to cell mechanisms activated due to drug resistance development and to methods of cell cultivation in the presence of drugs. The presented information provides an opportunity to discuss trends in the creation of chemoresistant cell lines for further research on resistance mechanisms and the development of new therapeutic strategies. Full article

(This article belongs to the Special Issue Multidrug Resistance in Cancer: Molecular Mechanisms and Therapeutic Challenges)

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20 pages, 6961 KB

Open AccessArticle

Antibiotics Impact the Cytotoxicity and Cytopathic Effect of Helicobacter pylori Extracellular Vesicles Against Gastric Cells

by Paweł Krzyżek, Mateusz Chmielarz, Edyta Bożemska, Agnieszka Opalińska, Mateusz Olbromski, Michał Małaszczuk, Barbara Krzyżanowska, Katarzyna Haczkiewicz-Leśniak, Marzenna Podhorska-Okołów, Piotr Dzięgiel and Beata Sobieszczańska

Int. J. Mol. Sci. 2025, 26(21), 10399; https://doi.org/10.3390/ijms262110399 (registering DOI) - 26 Oct 2025

Abstract

Helicobacter pylori is a spiral microorganism capable of inducing a range of gastric diseases. Among different virulence determinants produced by this bacterium, VacA and CagA are of critical importance for the development of these conditions. Taking into account the ability to chronically colonize [...] Read more.

Helicobacter pylori is a spiral microorganism capable of inducing a range of gastric diseases. Among different virulence determinants produced by this bacterium, VacA and CagA are of critical importance for the development of these conditions. Taking into account the ability to chronically colonize the stomach, drug-resistant strains of this pathogen can be repeatedly exposed to subinhibitory antibiotic concentrations, which in turn may reduce or enhance their extracellular vesicles (EVs)-derived virulence towards gastric cells. With the use of different experimental techniques, we were the first to demonstrate that subinhibitory antibiotic concentrations modify both the cytotoxicity and cytopathic effect induced by EVs of H. pylori in gastric cells. The ability to induce vacuolization and the hummingbird phenotype in gastric cells presented an antibiotic-specific pattern. At the highest doses tested, all EV types induced phenotypic changes and cytotoxicity in gastric cells; however, the highest lethal effect was observed for EVs isolated from native (antibiotic-unexposed) cells. This suggests that short-term exposure of H. pylori to subinhibitory antibiotic concentrations does not translate into exacerbation of its EVs-dependent virulence. Nevertheless, extensive research in this area is undoubtedly needed to confirm these observations. Full article

(This article belongs to the Section Molecular Microbiology)

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30 pages, 3105 KB

Open AccessArticle

Sumac Polyphenols as Pan-Herpesvirus Inhibitors

by Shavkat I. Salikhov, Yuliya I. Oshchepkova, Jamolitdin F. Ziyavitdinov, Jamshid M. Ashurov, Nodir S. Berdiev, Mikhail S. Kolundin, Akhmed O. Gaidarov, Ali S. Turgiev, Kirill I. Yurlov, Victor F. Larichev, Irina T. Fedyakina, Valeria L. Andronova, Natalia E. Fedorova, Alla A. Kushch, Alexander V. Ivanov and Eduard V. Karamov

Int. J. Mol. Sci. 2025, 26(21), 10398; https://doi.org/10.3390/ijms262110398 (registering DOI) - 26 Oct 2025

Abstract

Pandemic preparedness is a complex of threat-agnostic countermeasures developed in advance which would be efficient against a future outbreak regardless of its causative agent, and broad-spectrum antivirals constitute a critical component of this complex. Plant polyphenols are known to suppress viruses of unrelated [...] Read more.

Pandemic preparedness is a complex of threat-agnostic countermeasures developed in advance which would be efficient against a future outbreak regardless of its causative agent, and broad-spectrum antivirals constitute a critical component of this complex. Plant polyphenols are known to suppress viruses of unrelated families by acting on multiple viral and cellular structures. We therefore searched for broad-spectrum antivirals among polyphenols that have been confirmed as safe to humans. The ellagitannin geraniin and galloylglucose constituents of the drug Rutan (1,2,3,4,6-penta-O-galloyl-β-D-glucose [R5], 3-bis-O-galloyl-1,2,4,6-tetra-O-galloyl-β-D-glucose [R6], 2,4-bis-O-galloyl-1,3,6-tri-O-galloyl-β-D-glucose [R7], 2,3,4-bis-O-galloyl-1,6-di-O-galloyl-β-D-glucose [R8]) were isolated from Geranium sanguineum and sumac (Rhus coriaria), respectively. We revealed their activity towards herpes simplex viruses (HSV-1 and HSV-2), human cytomegalovirus (CMV), and the Epstein–Barr virus (EBV). R5 suppressed HSV-1 and HSV-2 with equal efficiency, while Rutan and R7 were more active against HSV-1, and geraniin against HSV-2. Rutan and R5 also inhibited the intracellular replication of CMV and EBV (contrary to our expectations, geraniin and polyphenols R6–R8 showed no activity). Thus, we have shown for the first time that sumac polyphenols are capable of suppressing—in addition to HIV, influenza virus, and SARS-CoV-2—the reproduction of representatives of all three Orthoherpesviridae subfamilies, meeting the criteria for further development as broad-spectrum antivirals. Full article

(This article belongs to the Special Issue Molecular View of Natural Products with Antiviral Effects)

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12 pages, 888 KB

Open AccessArticle

Improved Detection of Minimal Residual Disease in AML: Validation of IDH1/2 ddPCR Assays in the Perspective of Treatment with Target Inhibitors

by Katsiaryna Nikitsenka, Giacomo Danieli, Lucia Tombolan, Barbara Mancini, Davide Facchinelli, Giorgia Scotton, Alberto Tosetto, Omar Perbellini, Daniela Zuccarello and Elisabetta Novella

Int. J. Mol. Sci. 2025, 26(21), 10397; https://doi.org/10.3390/ijms262110397 (registering DOI) - 26 Oct 2025

Abstract

Mutations in IDH1/2 are frequent in Acute Myeloid Leukemia (AML), defining a molecularly distinct subgroup with therapeutic implications due to the availability of specific inhibitors. Accurate monitoring of treatment response is crucial and Droplet Digital PCR (ddPCR) offers a sensitive approach for quantifying [...] Read more.

Mutations in IDH1/2 are frequent in Acute Myeloid Leukemia (AML), defining a molecularly distinct subgroup with therapeutic implications due to the availability of specific inhibitors. Accurate monitoring of treatment response is crucial and Droplet Digital PCR (ddPCR) offers a sensitive approach for quantifying mutational burden in IDH-mutated AML. This study aimed to optimize and validate ddPCR assays specific for IDH1 R132 and IDH2 R172/R140 mutations for future use in Minimal Residual Disease (MRD) monitoring. Four ddPCR assays were set to evaluate the trend of IDH1/2 mutations in 191 diagnostic and follow-up samples. Each validation procedure included determining the limit of blank (LOB) and limit of detection (LOD) using titration series. Moreover, in AML harboring both IDH and NPM1 mutations, we performed generalized estimating equations (GEE) to assess the association between IDH fractional abundance and NPM1 RQ-Ratio across time points. Four IDH1/2 ddPCR assays were validated, demonstrating high sensitivity with limits of detection of 0.07% for IDH1 R132H, 0.1% for IDH2 R140Q and R172K, and 0.2% for IDH1 R132C. The method also exhibited excellent intra-run reproducibility, providing consistent results for patient follow-up. Comparison of IDH and NPM1 trends during follow-up revealed a statistically significant positive correlation, both in raw (β = 0.079, p = 0.001) and ranked data (β = 0.99, p = 0.004), suggesting a co-dynamic pattern potentially useful for surrogate monitoring. While our study cannot yet define the clinical role of IDH mutation assessment by ddPCR due to the lack of comparative follow-up studies, it establishes a solid methodological foundation for standardizing minimal residual disease evaluation via ddPCR, paving the way for future prospective validation. Full article

(This article belongs to the Special Issue Immunotherapy Versus Immune Modulation of Leukemia)

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13 pages, 891 KB

Open AccessCommunication

Gene Expression and Fatty Acid Composition in Sea Buckthorn Seeds and Pulp During Fruit Development of Different Varieties

by Nataliya V. Melnikova, Alexander A. Arkhipov, Yury A. Zubarev, Roman O. Novakovskiy, Anastasia A. Turba, Arthur G. Yablokov, Gleb N. Vladimirov, Sergey V. Osipenko, Anton A. Bashilov, Yury I. Kostyukevich, Eugene N. Nikolaev, Elizaveta A. Sigova, Ekaterina M. Dvorianinova, Daiana A. Krupskaya, Nikolai M. Barsukov, George S. Krasnov, Chengjiang Ruan, Elena N. Pushkova and Alexey A. Dmitriev

Int. J. Mol. Sci. 2025, 26(21), 10396; https://doi.org/10.3390/ijms262110396 (registering DOI) - 26 Oct 2025

Abstract

Sea buckthorn (Hippophae rhamnoides L.) is an oil crop with health benefits. Its fruits are rich in unsaturated fatty acids (FAs); however, the FA composition of the seeds and pulp differs significantly. To evaluate the expression levels of gene families that play [...] Read more.

Sea buckthorn (Hippophae rhamnoides L.) is an oil crop with health benefits. Its fruits are rich in unsaturated fatty acids (FAs); however, the FA composition of the seeds and pulp differs significantly. To evaluate the expression levels of gene families that play a major role in FA biosynthesis, the transcriptomes of seeds and pulp at four fruit development stages were sequenced for five sea buckthorn varieties with diverse characteristics: Elizaveta, Inya, KP-686, Panteleevskaya, and Triumf. The results revealed that FAD3 (07426) and FAD3 (05528) are likely key genes for linolenic acid synthesis in seeds, while FAD2 (21624) is likely the main contributor to linoleic acid synthesis in both seeds and pulp. SAD (18830) primarily contributes to oleic acid synthesis in seeds, while SAD (18830) and SAD (26748) contribute to its synthesis in pulp. FATA (14745) and FATA (14109) are also implicated in FA synthesis in sea buckthorn fruits. Changes in the content of the main FAs in seeds and pulp correlated with the expression levels of the corresponding genes. KP-686 and Triumf differed the most from other varieties. These results are important for analyzing tissue-specific gene expression in seeds and pulp of sea buckthorn fruits, and they are promising for developing sea buckthorn varieties with improved oil composition. Full article

(This article belongs to the Special Issue Genetics and Multi-Omics for Crop Breeding)

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14 pages, 1836 KB

Open AccessArticle

A Novel Surface Plasmon Resonance Imaging (SPRi) Biosensor for the Determination of Bovine Interleukin-10: Development, Validation, and Application in Biological Fluids

by Aleksandra Pytel, Dawid Tobolski, Piotr Skup, Justyna Gargaś, Sylwia Flis, Zdzisław Gajewski, Ewa Gorodkiewicz and Krzysztof Papis

Int. J. Mol. Sci. 2025, 26(21), 10395; https://doi.org/10.3390/ijms262110395 (registering DOI) - 25 Oct 2025

Abstract

Interleukin-10 (IL-10) is a pleiotropic cytokine that is pivotal in regulating the immune response. Its involvement in the pathophysiology of bovine diseases and its potential influence on oocyte developmental competence make it an important target for diagnostics and research. This study aimed to [...] Read more.

Interleukin-10 (IL-10) is a pleiotropic cytokine that is pivotal in regulating the immune response. Its involvement in the pathophysiology of bovine diseases and its potential influence on oocyte developmental competence make it an important target for diagnostics and research. This study aimed to develop and validate a novel, rapid, and sensitive analytical tool for its quantification. A specific biosensor based on Surface Plasmon Resonance Imaging (SPRi) was developed for the precise quantification of bovine IL-10, utilizing a polyclonal rabbit antibody immobilized on a gold chip for direct capture from complex biological matrices. The method was validated for its analytical performance, including linearity, sensitivity, precision, and selectivity. The developed method is characterized by a wide diagnostic range (1–1000 pg/mL) and high sensitivity, with a limit of detection (LOD) of 0.45 pg/mL and a limit of quantification (LOQ) of 1.49 pg/mL. The biosensor was successfully applied to measure IL-10 concentrations in bovine serum and follicular fluid, revealing significantly higher levels in follicular fluid. The validated SPRi biosensor is a rapid, sensitive, and cost-effective tool for determining IL-10 levels. Its successful application confirms its utility for veterinary diagnostics and highlights its potential for research in reproductive biology, particularly for assessing the follicular microenvironment. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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24 pages, 5353 KB

Open AccessArticle

Chitosan Nanoformulations of Mycosporine-like Amino Acid (MAA)-Rich Extracts from Mazzaella laminarioides Effectively Protect Human Keratinocytes Against UVA Radiation Damage

by Osmán Vásquez, Braulio Contreras-Trigo, Eileen Castillo, Neriel Contreras, Jessica Lemus, Felipe A. Zuniga, Karina Oyarce, Dariela Núñez, Víctor Díaz-García and Patricio Oyarzún

Int. J. Mol. Sci. 2025, 26(21), 10394; https://doi.org/10.3390/ijms262110394 (registering DOI) - 25 Oct 2025

Abstract

Mycosporine-like amino acids (MAAs) are secondary metabolites of interest for the development of natural sunscreens, owing to their antioxidant activity and ultraviolet radiation (UVR)-absorbing properties. MAA-rich aqueous extracts obtained from the Chilean red alga Mazzaella laminarioides (locally known as luga cuchara) were analyzed [...] Read more.

Mycosporine-like amino acids (MAAs) are secondary metabolites of interest for the development of natural sunscreens, owing to their antioxidant activity and ultraviolet radiation (UVR)-absorbing properties. MAA-rich aqueous extracts obtained from the Chilean red alga Mazzaella laminarioides (locally known as luga cuchara) were analyzed by HPLC and loaded into chitosan nanoparticles (CSNPs), with an encapsulation efficiency of 90.1%. The resulting CS nanoformulations (CSNFs) were characterized by FTIR spectroscopy, DLS and TEM microscopy, confirming the presence of nanoparticles with a core diameter of 94 ± 11 nm and FTIR absorption bands accounting for CS functional groups. Pre-treatment of HaCaT keratinocytes with CSNFs conferred complete protection against low-to-moderate UVA doses (5, 10, 15, and 30 J/cm²). Remarkably, cells still retained a protection efficacy of 64.7% under lethal UVA exposure (60 J/cm²), with gene expression evidence suggesting the activation of a compensatory stress response to photo-oxidative damage. CSNFs were also capable of restoring cell viability in post-treatment experiments at UVA doses of 30 J/cm² (100% cell viability) and 60 J/cm² (~43% cell viability). This is the first demonstration that nanoencapsulation of an MAA-rich algal extract yields superior UVA photoprotection in human keratinocytes compared with non-encapsulated MAA-based formulations, contributing to the effort of developing eco-friendly sunscreens. Full article

(This article belongs to the Special Issue Phyto-Functional Nanomaterials: Synthesis, Characterization and Application)

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9 pages, 1322 KB

Open AccessArticle

Heparin Provides Antiviral Activity Against Rhinovirus-16 via an Heparan Sulfate Proteoglycan-Independent Mechanism

by Leanne C. Helgers, Killian E. Vlaming, Tanja M. Kaptein, Julia Eder, Jan Willem Duitman and Teunis B. H. Geijtenbeek

Int. J. Mol. Sci. 2025, 26(21), 10393; https://doi.org/10.3390/ijms262110393 (registering DOI) - 25 Oct 2025

Abstract

Human rhinovirus 16 (HRV-16) is a major cause of common colds and can exacerbate asthma and COPD, yet no approved antiviral treatments exist. Heparin, a highly sulfated polysaccharide, is known to block viral infection of many viruses that require attachment to heparan sulfate [...] Read more.

Human rhinovirus 16 (HRV-16) is a major cause of common colds and can exacerbate asthma and COPD, yet no approved antiviral treatments exist. Heparin, a highly sulfated polysaccharide, is known to block viral infection of many viruses that require attachment to heparan sulfate proteoglycans (HSPGs). Here, we investigated whether heparin inhibits HRV-16 infection. HRV-16 uses ICAM-1 as its attachment receptor and lacks a confirmed HSPG-binding mechanism. Notably, heparin inhibited HRV-16 infection in vitro in a dose- and time-dependent manner. Pre-treatment of either cells or virus particles with unfractionated heparin significantly reduced HRV-16 RNA expression at 24 and 48 h post-infection. In contrast, low-molecular-weight heparins blocked infection of HRV-16 significantly less effectively compared to unfractionated heparins. Our findings suggest that the inhibitory effect of unfractionated heparin on HRV-16 infection is likely independent of specific HSPGs interactions and may be mediated by the size and highly negative charge of unfractionated heparin. Importantly, the ability of unfractionated heparin to block viruses that do not require HSPGs for attachment implies a broader antiviral potential as a prophylactic or therapeutic agent against a variety of respiratory viruses. Full article

(This article belongs to the Special Issue Respiratory Virus Infection)

19 pages, 1782 KB

Open AccessArticle

Evaluation of ¹⁶¹Tb-Labeled Diphosphonates as Potential Bone-Targeting Agents

by Pavle Sitarica, Aleksandar Vukadinović, Miloš Marić, Sanja Vranješ-Đurić, Dalibor Stanković, Marko Perić, Drina Janković, Dragana Stanković, Marija Mirković and Magdalena Radović

Int. J. Mol. Sci. 2025, 26(21), 10392; https://doi.org/10.3390/ijms262110392 (registering DOI) - 25 Oct 2025

Abstract

Two diphosphonates, etidronic acid (HEDP) and zoledronic acid (ZOL), were radiolabelled with ¹⁶¹Tb and evaluated as potential bone-targeting radiopharmaceuticals. Radiolabeling was performed at pH 7, achieving high radiolabeling yields (greater than 98%) and demonstrating excellent in vitro stability in saline and human [...] Read more.

Two diphosphonates, etidronic acid (HEDP) and zoledronic acid (ZOL), were radiolabelled with ¹⁶¹Tb and evaluated as potential bone-targeting radiopharmaceuticals. Radiolabeling was performed at pH 7, achieving high radiolabeling yields (greater than 98%) and demonstrating excellent in vitro stability in saline and human serum. Both radiolabeled complexes exhibited hydrophilic behavior, a strong binding affinity to hydroxyapatite, and moderate to high plasma protein binding. Biodistribution studies in healthy Wistar rats demonstrated that ¹⁶¹Tb-HEDP and ¹⁶¹Tb-ZOL achieve high and stable skeletal uptake with rapid blood clearance and minimal soft tissue accumulation. ¹⁶¹Tb-HEDP favored higher initial bone localization, while ¹⁶¹Tb-ZOL showed lower renal and hepatic accumulation, indicating higher safety and selectivity. Compared to unchelated ¹⁶¹TbCl₃, both diphosphonate complexes exhibited significantly higher bone-to-kidney and bone-to-liver ratios, resulting in superior targeting. Complementary experiments with non-radioactive terbium were performed to investigate the redox behavior and confirm complex formation, providing valuable insight into the stability and binding modes of the ligands. Both terbium and the ligands displayed well-defined redox behavior within the potential range of −1 to 1.7 V, with complex formation evidenced by shifts in the oxidation peaks. Density functional theory (DFT) calculations further supported these findings, showing that both phosphonate groups of a ligand coordinate to Tb³⁺, while the hydroxyl groups in HEDP enable intermolecular hydrogen bonding, contributing to additional structural stabilization. Results encourage further investigations of ¹⁶¹Tb-labeled diphosphonates as promising candidates for radionuclide therapy of bone metastases and other skeletal diseases. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 865 KB

Open AccessReview

Features of Peripheral T Cell Remigration into the Thymus

by Anastasiia A. Kalinina, Ludmila M. Khromykh and Dmitry B. Kazansky

Int. J. Mol. Sci. 2025, 26(21), 10391; https://doi.org/10.3390/ijms262110391 (registering DOI) - 25 Oct 2025

Abstract

The thymus, the central organ of T lymphopoiesis, is traditionally thought to exclusively export T cells. However, a great deal of studies has shown that mature peripheral T cells can return to the thymus and remain there. It is acknowledged that both CD4 [...] Read more.

The thymus, the central organ of T lymphopoiesis, is traditionally thought to exclusively export T cells. However, a great deal of studies has shown that mature peripheral T cells can return to the thymus and remain there. It is acknowledged that both CD4⁺ and CD8⁺ activated T cells can remigrate into the healthy adult thymus and accumulate predominantly in the medulla. In contrast, naïve T cells can actively populate the thymus of neonates and aged animals, potentially supporting the medulla’s functioning. Still, the fate and functions of peripheral T cell remigrants are not fully understood as of today. This review presents experimental findings on peripheral T cell remigration, analyzes phenotypic and traffic features of remigrants, and considers possible effects of backmigration on thymus function. Full article

(This article belongs to the Section Molecular Immunology)

15 pages, 1248 KB

Open AccessArticle

Serum Galectin-1 as a Diagnostic Biomarker in Endometriosis: A Prospective Longitudinal Study

by Reka Brubel, Dora Bianka Balogh, Beata Polgar, Laszlo Szereday, Gernot Hudelist, Nandor Acs and Attila Bokor

Int. J. Mol. Sci. 2025, 26(21), 10390; https://doi.org/10.3390/ijms262110390 (registering DOI) - 25 Oct 2025

Abstract

Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterine cavity. It affects ~10% of reproductive-aged individuals and is associated with dysmenorrhea and infertility. Although imaging modalities have improved diagnosis, laparoscopy is required in many cases, contributing to [...] Read more.

Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterine cavity. It affects ~10% of reproductive-aged individuals and is associated with dysmenorrhea and infertility. Although imaging modalities have improved diagnosis, laparoscopy is required in many cases, contributing to 4–11 years of diagnostic delay. Non-invasive biomarkers could improve diagnosis and clinical decision-making, yet no candidate has achieved sufficient accuracy for routine use. Galectins, a family of β-galactoside-binding lectins involved in angiogenesis, immune regulation, and fibrosis, have emerged as promising biomarkers. In this study, we measured serum Galectin-1 (Gal-1) concentrations in 80 women with endometriosis and 15 controls using ELISA at four time points. Preoperative Gal-1 levels were significantly higher in endometriosis patients, particularly in Stage III–IV disease. ROC analysis yielded a modest diagnostic performance (AUC 0.692; p = 0.011) with high sensitivity (91.3%) and excellent negative predictive value (96.8%) but low specificity (46.7%) at a study-derived threshold (>14.06 ng/mL). Longitudinally, Gal-1 levels decreased immediately after surgery and rose above baseline by one year, while no significant correlations with preoperative pain severity were observed. These findings suggest that serum Gal-1 alone is insufficient as a diagnostic test but may be useful for multi-marker strategies to improve early diagnosis. Full article

(This article belongs to the Special Issue Endometriosis and Infertility)

14 pages, 1624 KB

Open AccessArticle

A New Ursane-Type Pentacyclic Triterpenoid from the Tree Bark of Sandoricum koetjape: Antibacterial, DFT, and Molecular Docking Study

by Husnul Khatimah, Elvira Hermawati, Fadjar Mulya, Muhammad Ikhlas Abdjan, Thanawit Kuamit and Ade Danova

Int. J. Mol. Sci. 2025, 26(21), 10389; https://doi.org/10.3390/ijms262110389 (registering DOI) - 25 Oct 2025

Abstract

Natural products have played an important role in the discovery and development of antibacterial agents. This paper described the isolation of a new ursane-type pentacyclic triterpenoid, (18β,19αH)-3-oxo-urs-12-en-27α-oic acid (2), from the tree bark of Sandoricum koetjape Merr. Along with this, five [...] Read more.

Natural products have played an important role in the discovery and development of antibacterial agents. This paper described the isolation of a new ursane-type pentacyclic triterpenoid, (18β,19αH)-3-oxo-urs-12-en-27α-oic acid (2), from the tree bark of Sandoricum koetjape Merr. Along with this, five known compounds—β-caryophyllene oxide (1), bryononic acid (3), 7-deacetylgedunin (4), 7-deacetyl-7-oxogedunin (5), and 12,20-dihydroxydammar-24-en-3-one (6)—were successfully isolated, and one compound, 12β-hydroxydammarenolic acid (7), was reported in our previous report. All compounds (1–7) were tested with their antibacterial properties against two Gram-positive (Enterococcus faecalis and Staphylococcus saprophyticus) and two Gram-negative (Citrobacter freundii and Salmonella enterica) bacteria. The structures of the isolated compounds were elucidated using NMR spectroscopy and mass spectrometry data. A preliminary antibacterial assay showed that only compound 7 inhibited the growth of the tested bacteria, with an inhibition zone diameter of 7.5–9 mm at a concentration of 1 mg/mL. DFT analyses explained electronic profiles with HOMO-LUMO gaps (4.54–6.34 eV) and electrophilicity from 1.73 to 4.39 eV. To elucidate the antibacterial mechanism of compound 7, a molecular docking study was conducted. The findings from both in vitro and in silico analyses suggest that compound 7 is a promising antibacterial candidate for further investigation. Full article

(This article belongs to the Section Bioactives and Nutraceuticals)

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18 pages, 2782 KB

Open AccessArticle

STK38 Kinase Promotes Cell Migration Induced by Oncogenic Ras via MerTK Activation

by Satoshi Ohta, Kenji Tago, Katsumi Kasashima, Masayuki Ebina and Kaoru Tominaga

Int. J. Mol. Sci. 2025, 26(21), 10388; https://doi.org/10.3390/ijms262110388 (registering DOI) - 25 Oct 2025

Abstract

Ras gene mutations are frequently observed in many types of cancers. However, there are currently no effective anticancer drugs against Ras-induced cancers. Therefore, identifying the downstream effectors of the Ras signaling pathway can facilitate the development of promising novel therapeutic approaches. We previously [...] Read more.

Ras gene mutations are frequently observed in many types of cancers. However, there are currently no effective anticancer drugs against Ras-induced cancers. Therefore, identifying the downstream effectors of the Ras signaling pathway can facilitate the development of promising novel therapeutic approaches. We previously showed that oncogenic Ras induces the expression of the receptor tyrosine kinase c-Mer proto-oncogene tyrosine kinase (MerTK) in an interleukin-1 family member NF-HEV/IL-33-dependent manner and that IL-33 and MerTK contribute to oncogenic Ras-induced cell migration. In the present study, we purified the MerTK complex from NIH-3T3 cells transformed by the expression of oncogenic Ras, H-Ras (G12V). Mass spectrometric analysis identified STK38 (also known as NDR1) as a candidate binding partner for MerTK. STK38 is a serine/threonine protein kinase that plays diverse roles in normal and cancerous cells. In addition to MerTK knockdown, STK38 knockdown effectively attenuated the H-Ras (G12V)-induced migration of NIH-3T3 cells. STK38 kinase activity is required for oncogenic Ras-induced cell migration and MerTK tyrosine phosphorylation. Furthermore, MerTK or STK38 knockdown attenuated the activation of Rac1 and Cdc42. Taken together, these results revealed a novel role for STK38 in oncogenic Ras-induced enhanced cell migration, which may be useful for developing novel therapeutic strategies targeting Ras-mutated cells. Full article

(This article belongs to the Section Molecular Biology)

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30 pages, 9645 KB

Open AccessReview

Molecular Breeding for Fungal Resistance in Common Bean

by Luciana Lasry Benchimol-Reis, César Júnior Bueno, Ricardo Harakava, Alisson Fernando Chiorato and Sérgio Augusto Morais Carbonell

Int. J. Mol. Sci. 2025, 26(21), 10387; https://doi.org/10.3390/ijms262110387 (registering DOI) - 25 Oct 2025

Abstract

Despite the recognized social and economic importance of common beans (Phaseolus vulgaris L.), the average grain yield is far below the productive potential of cultivars. This situation is explained by several factors, such as the large number of diseases and pests that [...] Read more.

Despite the recognized social and economic importance of common beans (Phaseolus vulgaris L.), the average grain yield is far below the productive potential of cultivars. This situation is explained by several factors, such as the large number of diseases and pests that affect the crop, some of which cause significant damage. It is estimated that approximately 200 diseases can significantly affect common beans. These can be bacterial, viral, fungal, and nematode-induced. The main bean fungal diseases include anthracnose, angular leaf spot, powdery mildew, gray mold, Fusarium wilt, dry root rot, Pythium root rot, southern blight, white mold, charcoal rot and rust. This review provides a comprehensive overview of eleven major fungal diseases affecting common bean, describing their associated damage, characteristic symptomatology, and the epidemiological factors that favor disease development. It further synthesizes current knowledge on host resistance mechanisms that can be exploited to develop molecularly informed resistant genotypes. The compilation includes characterized resistance genes and mapped quantitative trait loci (QTLs), with details on their chromosomal locations, genetic effects, and potential for use in breeding. Moreover, the review highlights successful applications of molecular breeding approaches targeting fungal resistance. Finally, it discusses conclusions and future perspectives for integrating advanced genetic improvement strategies—such as marker-assisted selection, genomic selection, gene editing, and pyramiding—to enhance durable resistance to fungal pathogens in common bean. This work serves as both a reference for forthcoming resistance-mapping studies and a guide for the strategic selection of resistance loci in breeding programs aimed at developing cultivars with stable and long-lasting fungal resistance. Full article

(This article belongs to the Special Issue Plant Breeding and Genetics: New Findings and Perspectives)

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42 pages, 4110 KB

Open AccessReview

Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) in Inflammation and Disease: Mechanisms, Therapeutic Potential, and Future Directions

by Neerja Trivedi, Jitendra D. Bhosale, Amit Pant, Sonali P. Suryawanshi, Prerna Tiwari, Peter W. Abel and Gopal P. Jadhav

Int. J. Mol. Sci. 2025, 26(21), 10386; https://doi.org/10.3390/ijms262110386 (registering DOI) - 25 Oct 2025

Abstract

Triggering receptor expressed on myeloid cells-1 (TREM-1), a member of the immunoglobulin superfamily, plays a crucial role in amplifying inflammatory responses, thereby contributing to the pathogenesis and progression of various inflammatory diseases. This review presents a comprehensive analysis of the current understanding of [...] Read more.

Triggering receptor expressed on myeloid cells-1 (TREM-1), a member of the immunoglobulin superfamily, plays a crucial role in amplifying inflammatory responses, thereby contributing to the pathogenesis and progression of various inflammatory diseases. This review presents a comprehensive analysis of the current understanding of TREM-1 signaling and its dysregulation in disease pathology. Additionally, it explores the prognostic significance of TREM-1 across a spectrum of conditions. Targeting TREM-1 signaling represents a promising therapeutic approach for managing a wide range of diseases, including cancer, neurodegenerative disorders, cardiovascular diseases, and other inflammation-driven conditions. Previous reviews on TREM-1 have largely focused on its immunological role across diverse disease conditions and selective peptide-based inhibitors targeting its signaling pathway. However, recent discoveries have identified small-molecule modulators of TREM-1 that offer new opportunities for therapeutic intervention. Incorporating these findings would provide a more comprehensive and updated perspective on TREM-1 biology, particularly regarding its molecular regulation, drug-target potential, and translational relevance in inflammatory and immune-mediated disorders. Advances in this field are expected to be driven by structure-based drug design, particularly in the development of TREM-1 inhibitors. However, further research is needed to elucidate the predictive value of TREM-1 alterations and to evaluate them in prospective human studies prior to clinical decision-making. Full article

(This article belongs to the Section Molecular Biology)

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17 pages, 2190 KB

Open AccessArticle

Lidocaine Attenuates miRNA Dysregulation and Kinase Signaling Activation in a Porcine Model of Lung Ischemia/Reperfusion Injury

by Alberto Alonso, Sergio D. Paredes, Agustín Turrero, Lisa Rancan, Ignacio Garutti, Carlos Simón and Elena Vara

Int. J. Mol. Sci. 2025, 26(21), 10385; https://doi.org/10.3390/ijms262110385 (registering DOI) - 25 Oct 2025

Abstract

Ischemia/reperfusion (I/R) injury is a major complication in lung transplantation. Recent evidence suggests that mitogen-activated protein kinases (MAPKs) such as p-38 mitogen-activated protein kinase (p-38 MAPK) and extracellular signal-regulated kinase (ERK), along with functionally related kinases like phosphoinositide 3-kinase (PI3K) and protein kinase [...] Read more.

Ischemia/reperfusion (I/R) injury is a major complication in lung transplantation. Recent evidence suggests that mitogen-activated protein kinases (MAPKs) such as p-38 mitogen-activated protein kinase (p-38 MAPK) and extracellular signal-regulated kinase (ERK), along with functionally related kinases like phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), contribute to I/R pathophysiology by mediating inflammatory and stress-response signaling. MicroRNAs (miRNAs) also play a regulatory role in these processes. Lidocaine has demonstrated anti-inflammatory activity in several tissues; however, its ability to modulate miRNA expression and kinase activation in the lung is not yet fully understood. This study investigated the involvement of these signaling molecules in lung I/R injury and evaluated the modulatory effect of intravenous lidocaine in a porcine lung auto-transplantation model. Eighteen large white pigs were assigned to sham-operated (n = 6), control (lung auto-transplantation, n = 6), or lidocaine-treated (n = 6) groups. Lidocaine was administered as a 1.5 mg/kg bolus followed by a continuous infusion (1.5 mg·kg⁻¹·h⁻¹). Lung biopsies were collected before ischemia, before reperfusion, and at 30- and 60-min post-reperfusion to assess total and phosphorylated levels of p-38 MAPK, ERK, PI3K, and AKT (Thr308, Ser473), along with miR-126, miR-142-5p, miR-152, and miR-155 expression. I/R increased p-38 MAPK and AKT, and enhanced phosphorylation of all four kinases. miRNA levels were also upregulated. Lidocaine partially or completely attenuated these changes. These findings support a role for these molecular pathways in lung I/R injury and suggest that lidocaine may offer protective effects through their modulation. Full article

(This article belongs to the Special Issue New Molecular Insights into Ischemia/Reperfusion: 2nd Edition)

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13 pages, 748 KB

Open AccessArticle

Association Between Proinflammatory Cytokines IL-6 and TNF-Alpha, Psychological Stress and Chronic Spontaneous Urticaria Severity

by Liborija Lugović-Mihić, Maja Štrajtenberger, Matea Kuna, Blaženka Ladika-Davidović, Ema Barac and Maja Vilibić

Int. J. Mol. Sci. 2025, 26(21), 10384; https://doi.org/10.3390/ijms262110384 (registering DOI) - 25 Oct 2025

Abstract

Chronic urticaria (CU), defined as the appearance of wheals/angioedema lasting ≥6 weeks, is often associated with psychological factors like stress. Stress-induced reactions involve the psychological–neuroendocrine–immunological network, which influences disease course/outcome and patient quality of life (QoL). With 46 participants (23 with CU and [...] Read more.

Chronic urticaria (CU), defined as the appearance of wheals/angioedema lasting ≥6 weeks, is often associated with psychological factors like stress. Stress-induced reactions involve the psychological–neuroendocrine–immunological network, which influences disease course/outcome and patient quality of life (QoL). With 46 participants (23 with CU and 23 healthy controls/HCs), this research examined the relationship between values of serum proinflammatory cytokines (IL-6 and TNF-α), stress indicators (cortisol levels, perceived stress level), and clinical chronic spontaneous urticaria (CSU) features (CSU severity/UAS, patient QoL). For CSU patients, significantly higher levels of IL-6 (p = 0.002) and TNF-α (p = 0.001) were recorded, as well as higher cortisol levels (p = 0.015) and a lower perception of stress/PSS (p < 0.001) than for HCs. CSU severity linearly and positively correlated with serum cortisol level (r = 0.463; p = 0.463) and impaired QoL (r = 0.715; p < 0.001). Additionally, impaired QoL correlated positively with perceived stress (r = 0.523; p = 0.010) and negatively with age (r = −0.529; p = 0.009). Also, IL-6 levels negatively correlated with perceived stress (r = −0.402; p = 0.006) linearly and moderately. The significant negative correlation between psychological stress and CU indicates that a comprehensive approach to treatment is necessary. Full article

(This article belongs to the Special Issue Dialogue Between Inflammation and Immunity: From Mechanism to Therapy)

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19 pages, 8910 KB

Open AccessArticle

Oxidized Hyaluronic Acid-Based Sponges: A Promising Biomaterial for Oral Mucosa Lesion Application

by Clara Alicia Muñoz-Trejo, Martha Gabriela Chuc-Gamboa, Juan V. Cauich-Rodríguez, Rossana Faride Vargas-Coronado, Diana María Escobar-García, Amaury Pozos-Guillen, Fernando Javier Aguilar-Pérez, Alicia Leonor Pinzon-Te and Gualberto Antonio Zumbardo-Bacelis

Int. J. Mol. Sci. 2025, 26(21), 10383; https://doi.org/10.3390/ijms262110383 (registering DOI) - 25 Oct 2025

Abstract

Chitosan (CHT) and hyaluronic acid (HA) are biomaterials with diverse properties. While each has been individually employed for the treatment of oral lesions, there is a need for further evidence regarding their combined properties. This study compares the effects on the properties and [...] Read more.

Chitosan (CHT) and hyaluronic acid (HA) are biomaterials with diverse properties. While each has been individually employed for the treatment of oral lesions, there is a need for further evidence regarding their combined properties. This study compares the effects on the properties and biocompatibility of chitosan sponges, CHT crosslinked with oxidized hyaluronic acid (OHA) (oxidized at 1:1 and 1:2 ratios, respectively), and CHT crosslinked with oxidized hyaluronic acid and polyethylene glycol diglycidyl ether (PEGDE). Spectroscopy revealed reduced free amino groups and the amide I/II ratio in CHT sponges crosslinked with OHA. SEM confirmed the porous network morphology with an average pore size ranging from 155 to 213 μm. TGA indicated the scaffolds’ decomposition temperature (Td) increased from 253° to 308°, with the CHT-OHA 1:2 sponge exhibiting the highest thermal stability. Compression testing highlighted that the chitosan sponges crosslinked with AHO and PEGDE at a 1:2 ratio displayed a higher elastic modulus than the other studied scaffolds. The MTS assay confirmed that the fabricated biomaterials were not cytotoxic. This study demonstrates the enhanced properties and biocompatibility of CHT-OHA and CHT-OHA-PEGDE sponges, highlighting their potential for oral lesion treatment. Full article

(This article belongs to the Special Issue Application of Biotechnology to Dental Treatment)

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4 pages, 171 KB

Open AccessEditorial

Special Issue “Viral Infections and Host Immune Responses”

by Maria Teresa Maggiorella and Barbara Ridolfi

Int. J. Mol. Sci. 2025, 26(21), 10382; https://doi.org/10.3390/ijms262110382 (registering DOI) - 25 Oct 2025

Abstract

The emergence of viral epidemics, climate change, and population migration has resulted in greater vulnerability to the transmission of old, new, and re-emerging infectious diseases [...] Full article

(This article belongs to the Special Issue Viral Infections and Host Immune Responses)

32 pages, 415 KB

Open AccessReview

Ferroptosis in the Ovarian Follicular Microenvironment: A Redox-Dependent Cell Death Pathway with Emerging Roles in PCOS, Oocyte Quality, and IVF Outcomes

by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Spyridon Polykalas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Maria Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis K. Papapanagiotou, Dimitrios Vaitsis, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis Show full author list Hide full author list

Int. J. Mol. Sci. 2025, 26(21), 10381; https://doi.org/10.3390/ijms262110381 (registering DOI) - 25 Oct 2025

Abstract

Ferroptosis is a novel kind of regulated cell death that occurs when redox equilibrium is disrupted, leading to iron-dependent lipid peroxidation. Ferroptosis is defined by the buildup of deleterious lipid hydroperoxides, the inactivation of glutathione peroxidase 4 (GPX4), and mitochondrial shrinkage, setting it [...] Read more.

Ferroptosis is a novel kind of regulated cell death that occurs when redox equilibrium is disrupted, leading to iron-dependent lipid peroxidation. Ferroptosis is defined by the buildup of deleterious lipid hydroperoxides, the inactivation of glutathione peroxidase 4 (GPX4), and mitochondrial shrinkage, setting it apart from apoptosis and necrosis. The relevance of this route to human reproduction remains unknown, despite its thorough investigation in neurodegeneration and cancer. Recent studies demonstrate that the ovarian follicular milieu is especially susceptible to ferroptosis owing to its high content of polyunsaturated fatty acids, iron-dependent metabolism, and the generation of reactive oxygen species. Dysregulation of ferroptosis may result in infertility by affecting granulosa cell survival, oocyte maturation, and embryonic competence. Ferroptotic activity correlates with oxidative stress indicators identified in clinical diseases including polycystic ovary syndrome, reduced ovarian reserve, and insufficient responsiveness to ovarian stimulation. Potential indicators include GPX4 expression, decreased glutathione levels, and the accumulation of lipid reactive oxygen species in granulosa cells and follicular fluid. Melatonin, which boosts antioxidant defences, and ferrostatin-1, a prototype inhibitor of ferroptosis that lowers lipid peroxidation, are two early candidates for treatment. For future evaluations, these agents should be used with standardised FF biomarker panels. Significantly, vitamin E, coenzyme Q10, and small-molecule ferroptosis inhibitors have shown efficacy in halting ferroptosis in experimental settings. These approaches have shown protective benefits in alternative systems and may signify viable treatment options for assisted reproduction. This narrative review encapsulates ferroptosis inside the ovarian follicle, its influence on oocyte quality, and the implications for in vitro fertilization results. Full article

(This article belongs to the Special Issue Redox Homeostasis and Oxidative Stress in Human Metabolism and Disease：2nd Edition)

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Int. J. Mol. Sci., Volume 26, Issue 21 (November-1 2025) – 166 articles

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