International Journal of Molecular Sciences

27 pages, 16635 KiB

Open AccessArticle

Revealing the Role of Beesioside O from Actaea vaginata for the Treatment of Breast Cancer Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

by Shuyang Li, Juan Lu, Hongwei Xue, Yang Lou, Jia Liu, Yutian Wang, Haifeng Wu and Xi Chen

Int. J. Mol. Sci. 2025, 26(5), 2283; https://doi.org/10.3390/ijms26052283 (registering DOI) - 4 Mar 2025

Abstract

Breast cancer remains a leading cause of malignancy-related mortality among women, with rising global incidence. While surgical intervention is effective for early-stage breast cancer, drug therapy is indispensable, particularly for triple-negative breast cancer, where treatment options are still limited. Actaea vaginata, a [...] Read more.

Breast cancer remains a leading cause of malignancy-related mortality among women, with rising global incidence. While surgical intervention is effective for early-stage breast cancer, drug therapy is indispensable, particularly for triple-negative breast cancer, where treatment options are still limited. Actaea vaginata, a traditional Chinese medicinal herb, has been historically applied for inflammatory conditions, including pharyngitis and stomatitis. However, its antitumor potential remains under-reported. In this study, a cycloartane triterpene saponin, beesioside O (BO), was isolated from this plant. Its antitumor activity was evaluated in vitro. Its potential therapeutic mechanisms were elucidated through network pharmacology. BO exhibited substantial potency in inhibiting breast cancer cells. Network pharmacology analysis uncovered 179 potential pharmacological targets of BO, which were predominantly concentrated in pathways, such as pathways in cancer, the PI3K-Akt signaling pathway, and chemical carcinogenesis receptor activation. Molecular docking analysis indicated that STAT3 exhibited minimal binding energy with BO. Additionally, molecular dynamics simulations verified the conformational stability of the BO-STAT3 complex. Western blot analysis demonstrated that STAT3 was downregulated following administration. These results imply that BO may exhibit a multi-target, synergistic therapeutic effect against breast cancer, with STAT3 recognized as a pivotal target. This study demonstrates the potential of BO for development as a chemotherapeutic agent for breast cancer treatment. It lays the groundwork for further exploration of BO’s bioactivity and provides valuable insights into its molecular mechanisms in breast cancer therapy. Full article

(This article belongs to the Special Issue Molecular Modeling: Latest Advances and Applications)

► Show Figures

Figure 1

11 pages, 672 KiB

Open AccessReview

The Role of Temperature on Inflammation and Coagulation: Should We Apply Temperature Treatments for Hemophilic Arthropathy?

by Alice Maria Brancato, Laura Caliogna, Alessandra Monzio Compagnoni, Elena Cornella, Camilla Torriani, Micaela Berni, Liliana De Felice, Eugenio Jannelli, Mario Mosconi and Gianluigi Pasta

Int. J. Mol. Sci. 2025, 26(5), 2282; https://doi.org/10.3390/ijms26052282 (registering DOI) - 4 Mar 2025

Abstract

Hemophilic arthropathy (HA) is a complication of hemophilia, which is a genetic disorder characterized by a deficiency in blood clotting factors. HA is characterized by joint damage with inflammatory responses, pain, and movement limitations due to recurrent bleeding in the joints. The inflammatory [...] Read more.

Hemophilic arthropathy (HA) is a complication of hemophilia, which is a genetic disorder characterized by a deficiency in blood clotting factors. HA is characterized by joint damage with inflammatory responses, pain, and movement limitations due to recurrent bleeding in the joints. The inflammatory reactions contribute to the activation of coagulation factors, which can exacerbate bleeding and further damage the affected joints. Therefore, the interaction between inflammation and coagulation plays a crucial role in the progression and complications of HA. Management strategies often focus both on inflammation and coagulation to alleviate symptoms and preserve joint function. Temperature can influence the inflammatory response and coagulation. The aim of this work was to understand how temperature management can positively or negatively influence the HA. We have carried out a narrative review of the available literature. This review explores the impacts of temperature on biological processes, and it discusses the possible clinical implications for the HA treatment. Our research shows that cold exposure has anti-inflammatory and analgesic effects, while heat is linked to pro-inflammatory cytokine release. Both hot and cold treatments are ill-advised for hemophilia patients. Heat stimulates neo-angiogenesis, and cold hampers coagulation, posing risks for increased bleeding in individuals with hemophilia. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: Inflammation, Degeneration or Mechanical Stress)

► Show Figures

Figure 1

21 pages, 6788 KiB

Open AccessArticle

A Feature Engineering Method for Whole-Genome DNA Sequence with Nucleotide Resolution

by Ting Wang, Yunpeng Cui, Tan Sun, Huan Li, Chao Wang, Ying Hou, Mo Wang, Li Chen and Jinming Wu

Int. J. Mol. Sci. 2025, 26(5), 2281; https://doi.org/10.3390/ijms26052281 - 4 Mar 2025

Abstract

Feature engineering for whole-genome DNA sequences plays a critical role in predicting plant phenotypic traits. However, due to limitations in the models’ analytical capabilities and computational resources, the existing methods are predominantly confined to SNP-based approaches, which typically extract genetic variation sites for [...] Read more.

Feature engineering for whole-genome DNA sequences plays a critical role in predicting plant phenotypic traits. However, due to limitations in the models’ analytical capabilities and computational resources, the existing methods are predominantly confined to SNP-based approaches, which typically extract genetic variation sites for dimensionality reduction before feature extraction. These methods not only suffer from incomplete locus coverage and insufficient genetic information but also overlook the relationships between nucleotides, thereby restricting the accuracy of phenotypic trait prediction. Inspired by the parallels between gene sequences and natural language, the emergence of large language models (LLMs) offers novel approaches for addressing the challenge of constructing genome-wide feature representations with nucleotide granularity. This study proposes FE-WDNA, a whole-genome DNA sequence feature engineering method, using HyenaDNA to fine-tune it on whole-genome data from 1000 soybean samples. We thus provide deep insights into the contextual and long-range dependencies among nucleotide sites to derive comprehensive genome-wide feature vectors. We further evaluated the application of FE-WDNA in agronomic trait prediction, examining factors such as the context window length of the DNA input, feature vector dimensions, and trait prediction methods, achieving significant improvements compared to the existing SNP-based approaches. FE-WDNA provides a mode of high-quality DNA sequence feature engineering at nucleotide resolution, which can be transformed to other plants and directly applied to various computational breeding tasks. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

► Show Figures

Figure 1

14 pages, 1700 KiB

Open AccessArticle

miRNA-Based Diagnosis of Schizophrenia Using Machine Learning

by Vishrut Heda, Saanvi Dogra, Valentina L. Kouznetsova, Alex Kumar, Santosh Kesari and Igor F. Tsigelny

Int. J. Mol. Sci. 2025, 26(5), 2280; https://doi.org/10.3390/ijms26052280 - 4 Mar 2025

Abstract

Diagnostic practices for schizophrenia are unreliable due to the lack of a stable biomarker. However, machine learning holds promise in aiding in the diagnosis of schizophrenia and other neurological disorders. Dysregulated miRNAs were extracted from public sources. Datasets of miRNAs selected from the [...] Read more.

Diagnostic practices for schizophrenia are unreliable due to the lack of a stable biomarker. However, machine learning holds promise in aiding in the diagnosis of schizophrenia and other neurological disorders. Dysregulated miRNAs were extracted from public sources. Datasets of miRNAs selected from the literature and random miRNAs with designated gene targets along with related pathways were assigned as descriptors of machine-learning models. These data were preprocessed and classified using WEKA and TensorFlow, and several classifiers were tested to train the model. The Sequential neural network developed by authors performed the best of the classifiers tested, achieving an accuracy of 94.32%. Naïve Bayes was the next best model, with an accuracy of 72.23%. MLP achieved an accuracy of 65.91%, followed by Hoeffding tree with an accuracy of 64.77%, Random tree with an accuracy of 63.64%, Random forest, which achieved an accuracy of 61.36%, and lastly ADABoostM1, which achieved an accuracy of 53.41%. The Sequential neural network and Naïve Bayes classifier were tested to validate the model as they achieved the highest accuracy. Naïve Bayes achieved a validation accuracy of 72.22%, whereas the sequential neural network achieved an accuracy of 88.88%. Our results demonstrate the practicality of machine learning in psychiatric diagnosis. Dysregulated miRNA combined with machine learning can serve as a diagnostic aid to physicians for schizophrenia and potentially other neurological disorders as well. Full article

(This article belongs to the Special Issue Molecular Modeling: Latest Advances and Applications)

► Show Figures

Figure 1

20 pages, 1954 KiB

Open AccessArticle

Inflammatory Biomarkers and Oral Health Disorders as Predictors of Head and Neck Cancer: A Retrospective Longitudinal Study

by Amr Sayed Ghanem, Kitti Sipos, Ágnes Tóth and Attila Csaba Nagy

Int. J. Mol. Sci. 2025, 26(5), 2279; https://doi.org/10.3390/ijms26052279 - 4 Mar 2025

Abstract

Head and neck cancers (HNCs) are often diagnosed late, leading to poor prognosis. Chronic inflammation, particularly periodontitis, has been linked to carcinogenesis, but systemic inflammatory markers remain underexplored. This study was the first to examine whether elevated C-reactive protein (CRP) can serve as [...] Read more.

Head and neck cancers (HNCs) are often diagnosed late, leading to poor prognosis. Chronic inflammation, particularly periodontitis, has been linked to carcinogenesis, but systemic inflammatory markers remain underexplored. This study was the first to examine whether elevated C-reactive protein (CRP) can serve as a cost-effective adjunct in HNC risk assessment, alongside oral health indicators. A retrospective cohort study analysed 23,742 hospital records (4833 patients, 2015–2022) from the University Hospital of Debrecen. HNC cases were identified using ICD-10 codes, with CRP and periodontitis as key predictors. Kaplan–Meier survival analysis, log-rank tests, and Weibull regression were used to assess risk, with model performance evaluated via AIC/BIC and ROC curves. Periodontitis was significantly associated with HNC (HR 5.99 [1.96–18.30]), while elevated CRP (>15 mg/L) independently increased risk (HR 4.16 [1.45–12.00]). Females had a significantly lower risk than males (HR 0.06 [0.01–0.50]). CRP may serve as a cost-effective, easily accessible biomarker for early HNC detection when combined with oral health screening. Integrating systemic inflammation markers into HNC risk assessment models could potentially improve early diagnosis in high-risk populations. Full article

(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)

► Show Figures

Figure 1

34 pages, 1786 KiB

Open AccessReview

Medicinal Plant Extracts Targeting UV-Induced Skin Damage: Molecular Mechanisms and Therapeutic Potential

by Chunhui Zhao, Shiying Wu and Hao Wang

Int. J. Mol. Sci. 2025, 26(5), 2278; https://doi.org/10.3390/ijms26052278 - 4 Mar 2025

Abstract

The depletion of the ozone layer has intensified ultraviolet (UV) radiation exposure, leading to oxidative stress, DNA damage, inflammation, photoaging, and skin cancer. Medicinal plants, widely used in Traditional Herbal Medicine (THM), particularly in Traditional Chinese Medicine (TCM), have demonstrated significant therapeutic potential [...] Read more.

The depletion of the ozone layer has intensified ultraviolet (UV) radiation exposure, leading to oxidative stress, DNA damage, inflammation, photoaging, and skin cancer. Medicinal plants, widely used in Traditional Herbal Medicine (THM), particularly in Traditional Chinese Medicine (TCM), have demonstrated significant therapeutic potential due to their well-characterized active compounds and established photoprotective effects. This review systematically evaluates 18 medicinal plants selected based on their traditional use in skin-related conditions and emerging evidence supporting their efficacy against UV-induced skin damage. Their bioactive components exert antioxidant, anti-inflammatory, DNA repair, and depigmentation effects by modulating key signaling pathways, including Nrf2/ARE-, MAPK/AP-1-, PI3K/Akt-, and MITF/TYR-related melanogenesis pathways. Moreover, novel drug delivery systems, such as exosomes, hydrogels, and nanoemulsions, have significantly enhanced the stability, bioavailability, and skin penetration of these compounds. However, challenges remain in standardizing plant-derived formulations, elucidating complex synergistic mechanisms, and translating preclinical findings into clinical applications. Future interdisciplinary research and technological advancements will be essential to harness the full therapeutic potential of medicinal plants for UV-induced skin damage prevention and treatment. Full article

(This article belongs to the Special Issue Novel Natural Compound for Wound and Tissue Repair and Regeneration: 3rd Edition)

► Show Figures

Figure 1

18 pages, 8616 KiB

Open AccessArticle

Exploring Metabolic Pathways and Gene Mining During Cotton Flower Bud Differentiation Stages Based on Transcriptomics and Metabolomics

by Miaoqian Yang, Wenjie Li, Xiaokang Fu, Jianhua Lu, Liang Ma, Hantao Wang and Hengling Wei

Int. J. Mol. Sci. 2025, 26(5), 2277; https://doi.org/10.3390/ijms26052277 - 4 Mar 2025

Abstract

Cotton is regarded as one of the significant economic crops in China, and its earliness is defined as one of the crucial traits influencing fiber quality and yield. To study the physiological and biochemical mechanisms related to early-maturing traits of cotton, cotton shoot [...] Read more.

Cotton is regarded as one of the significant economic crops in China, and its earliness is defined as one of the crucial traits influencing fiber quality and yield. To study the physiological and biochemical mechanisms related to early-maturing traits of cotton, cotton shoot apexes at the one-leaf, three-leaf, and five-leaf stages of the early-maturing cotton CCRI50 and late-maturing cotton Guoxinmian11 were collected for transcriptome sequencing and metabolomics, respectively. A total of 616, 782, and 842 differentially expressed genes (DEGs) at the one-leaf stage, three-leaf stage, and five-leaf stage were obtained through transcriptome sequencing, respectively. The metabolic detection results showed that 68, 56, and 62 differential metabolites (DMs) were obtained in the three periods, respectively. A total of 10 DMs were detected simultaneously from the one-leaf to five-leaf stage, 4 of which were phenolic acids and down-regulated in the early maturing variety CCRI50. A combined transcriptomic and metabolomic analysis revealed that phenylpropanoid biosynthesis, tyrosine metabolism, and phenylalanine metabolism might be important metabolic pathways in cotton bud differentiation. GhTYDC-A01 was identified in both the tyrosine metabolism and phenylalanine metabolism pathways, and it was highly expressed in pistils. To investigate the function of this gene in flowering, we overexpressed it in Arabidopsis thaliana. Compared to the wild type, the flowering time of the overexpression of GhTYDC-A01 in Arabidopsis was delayed. This study provides valuable resources and new insights into the relationship between metabolites and early-maturing cotton. Full article

(This article belongs to the Special Issue Genes Function and Mechanism Identification in Plant Stress Resistance: 3rd Edition)

► Show Figures

Figure 1

17 pages, 8951 KiB

Open AccessArticle

NAD⁺ Promotes Superovulation of Huaxi Cattle Through Regulation of Cumulus Cell Proliferation and Oocyte Maturation

by Song Wang, Mingcheng Liu, Anqi Di, Xiqing Jiang, Junjia Wu, Jiandong Zhang, Xuefei Liu, Chunling Bai, Guanghua Su, Lishuang Song, Guangpeng Li, Zhonghua Liu and Lei Yang

Int. J. Mol. Sci. 2025, 26(5), 2276; https://doi.org/10.3390/ijms26052276 - 4 Mar 2025

Abstract

Superovulation and embryo transfer are key technologies to improve the reproductive ability of female animals and enhance the efficiency of livestock production. However, poor-quality oocytes or abnormal fluctuations of hormone levels caused by superovulation affect the embryonic development environment, which may lead to [...] Read more.

Superovulation and embryo transfer are key technologies to improve the reproductive ability of female animals and enhance the efficiency of livestock production. However, poor-quality oocytes or abnormal fluctuations of hormone levels caused by superovulation affect the embryonic development environment, which may lead to a significant decline in the number and quality of transferable embryos, thus reducing the efficiency of superovulation. In this study, nicotinamide adenine dinucleotide (NAD⁺) was injected into Huaxi cows during the superovulation period to observe the proliferation and apoptosis of transplanted embryos. We examined the proliferation, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential of cumulus cells and oocytes directly treated with NAD⁺ and investigated the potential mechanism of NAD⁺ to improve the superovulation efficiency by serum metabolomics and single-cell RNA sequencing. The results show that the addition of NAD⁺ significantly increased the quantity and quality of transferable embryos after superovulation. Differential metabolites during estrus synchronization and embryo flushing are enriched in glycerophospholipid metabolic pathways, suggesting that NAD⁺ can regulate lipid metabolic pathways. We found that NAD⁺ optimized the secretion levels of the steroid hormone estradiol (E2) and progesterone (P4) during superovulation by regulating the activity of cumulus cells. In oocytes, we found that NAD⁺ can inhibit apoptosis, scavenge ROS, and enhance mitochondrial function, thereby promoting oocyte maturation and enhancing embryo developmental potential. In conclusion, NAD⁺ significantly improved the superovulation ability of Huaxi cattle and provides an effective way for animal husbandry to improve the yield of high-quality embryos. Full article

(This article belongs to the Section Molecular Biology)

► Show Figures

Figure 1

26 pages, 2602 KiB

Open AccessReview

Nutrients Lowering Obesity-Linked Chemokines Blamable for Metastasis

by Gabriela Ion, Marinela Bostan, Wanda Elaine Hardman, Margaret Putt McFarland, Coralia Bleotu, Nicoleta Radu, Carmen Cristina Diaconu, Mirela Mihaila, Mihai Dan Caramihai and Camelia Mia Hotnog

Int. J. Mol. Sci. 2025, 26(5), 2275; https://doi.org/10.3390/ijms26052275 - 4 Mar 2025

Abstract

Food intake is an essential contributor to both health and disease. Nutrients contribute to a beneficial metabolic equilibrium at the cellular level, preventing or delaying disease onset. Dietary intake contributes to obesity, and obesity supports further cancer and metastasis. Metastasis, a multifactorial and [...] Read more.

Food intake is an essential contributor to both health and disease. Nutrients contribute to a beneficial metabolic equilibrium at the cellular level, preventing or delaying disease onset. Dietary intake contributes to obesity, and obesity supports further cancer and metastasis. Metastasis, a multifactorial and multistep process, is supported by the systemic inflammation of obesity. Spreading of the cancer cells requires the presence of a plethora of recruiter and regulator molecules. Molecules such as chemokines are provided at high levels by obesity-associated fat depots. Chemokine up-regulation in adipose tissue of obese individuals has been associated with different types of cancers such as breast, prostate, colon, liver, and stomach. Chemokines support all metastasis steps from invasion/migration to intravasation, circulation, extravasation, and ending with colonization. The obesity pool of chemokines supporting these processes includes CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL18, CCL19, CCL20, CXCL1, CXCL5, CXCL 8, CXCL10, and CXCL12. Keeping obesity under control can be beneficial in reducing the levels of pro-inflammatory chemokines and the risk of poor cancer outcome. Nutrients can help, support, and boost cancer treatment effects or jeopardize the treatment. Constituents with anti-inflammatory and anti-obesity properties such as polyphenols, organosulfur components, fatty acids, curcumin, and vitamin E have a proven beneficial effect in lowering obesity and its contribution to metastasis. Full article

(This article belongs to the Special Issue Natural Products in Cancer Prevention and Treatment)

► Show Figures

Figure 1

18 pages, 1466 KiB

Open AccessArticle

The Novel Role of the Expression of Toll-like Receptors TLR-5, TLR-6, and TLR-9 and Associated Up-Regulation of Programmed Cell Death 1 Receptor (PD-1) and Its Ligand (PD-L1) in Lung Sepsis

by Georgios Sinos, Dimitrios Schizas, Alkistis Kapelouzou, Maximos Frountzas, Michalis Katsimpoulas, Konstantinos S. Mylonas, Emmanouil I. Kapetanakis, Alexandros Papalampros, Theodore Liakakos and Andreas Alexandrou

Int. J. Mol. Sci. 2025, 26(5), 2274; https://doi.org/10.3390/ijms26052274 - 4 Mar 2025

Abstract

Sepsis is a leading cause of death in hospitalized patients. The underlying pathophysiologic mechanisms of sepsis have not been fully elucidated thus far. The receptor of programmed cell death 1 (PD-1) and its ligand (PD-L1), in combination with the Toll-like receptors (TLRs), seem [...] Read more.

Sepsis is a leading cause of death in hospitalized patients. The underlying pathophysiologic mechanisms of sepsis have not been fully elucidated thus far. The receptor of programmed cell death 1 (PD-1) and its ligand (PD-L1), in combination with the Toll-like receptors (TLRs), seem to contribute considerably in systematic responses during sepsis. Investigating the relationship between them and identifying potential target pathways is important in the future management of sepsis, especially in relation to acute lung injury. This study investigated the interactions between TLR-5, -6, and -9 and PD-1/PD-L1 expression in a septic mouse model. Sixty C57BL/6J mice were included and categorized in six study groups. Three sepsis (S) groups (24 h, 48 h, and 72 h) and three sham (Sh) groups (24 h, 48 h, and 72 h) were created. Cecal ligation and puncture (CLP) was utilized to simulate sepsis in the S groups. Hematological analysis and lung tissue histopathological analysis were performed after 24 h, 48 h, and 72 h. Significant decreases in S groups compared to Sh groups in WBC and lymphocyte counts at 24, 48, and 72 h were observed. Significant increases in S groups compared to Sh groups in RBC and monocyte counts, IL-6 and IL-10 levels, alveolar flooding, and alveolar collapse were demonstrated by histopathological analysis. This study suggested a strong correlation between TLR expression and PD-1/PD-L1 up-regulation in lung tissue during sepsis. These molecules, also, seem to contribute to the histopathological changes in lung tissue during sepsis, leading to acute lung injury. Full article

(This article belongs to the Special Issue Molecular Advances in Congenital and Adult Cardiac Surgery: From Genes to Grafts)

► Show Figures

Figure 1

1 pages, 137 KiB

Open AccessCorrection

Correction: Han et al. Genotypic Homogeneity in Distinctive Transforming Growth Factor-Beta-Induced (TGFBI) Protein Phenotypes. Int. J. Mol. Sci. 2021, 22, 1230

by Sang Beom Han, Venkatraman Anandalakshmi, Chee Wai Wong, Si Rui Ng and Jodhbir S. Mehta

Int. J. Mol. Sci. 2025, 26(5), 2273; https://doi.org/10.3390/ijms26052273 - 4 Mar 2025

Abstract

There was an error in the original publication [...] Full article

(This article belongs to the Section Molecular Genetics and Genomics)

24 pages, 6406 KiB

Open AccessArticle

Lectin-Based Substrate Detection in Fabry Disease Using the Gb3-Binding Lectins StxB and LecA

by Serap Elçin-Guinot, Simon Lagies, Yoav Avi-Guy, Daniela Neugebauer, Tobias B. Huber, Christoph Schell, Bernd Kammerer and Winfried Römer

Int. J. Mol. Sci. 2025, 26(5), 2272; https://doi.org/10.3390/ijms26052272 - 4 Mar 2025

Abstract

Fabry disease, the second most common lysosomal storage disorder, is caused by a deficiency of α-galactosidase A (α-Gal A), which leads to an accumulation of glycosphingolipids (GSL), mainly globotriaosylceramide (also known as Gb3). This aberrant GSL metabolism subsequently causes cellular dysfunction; however, the [...] Read more.

Fabry disease, the second most common lysosomal storage disorder, is caused by a deficiency of α-galactosidase A (α-Gal A), which leads to an accumulation of glycosphingolipids (GSL), mainly globotriaosylceramide (also known as Gb3). This aberrant GSL metabolism subsequently causes cellular dysfunction; however, the underlying cellular and molecular mechanisms are still unknown. There is growing evidence that damage to organelles, including lysosomes, mitochondria, and plasma membranes, is associated with substrate accumulation. Current methods for the detection of Gb3 are based on anti-Gb3 antibodies, the specificity and sensitivity of which are problematic for glycan detection. This study presents a robust method using lectins, specifically the B-subunit of Shiga toxin (StxB) from Shigella dysenteriae and LecA from Pseudomonas aeruginosa, as alternatives for Gb3 detection in Fabry fibroblasts by flow cytometry and confocal microscopy. StxB and LecA showed superior sensitivity, specificity, and consistency in different cell types compared to all anti-Gb3 antibodies used in this study. In addition, sphingolipid metabolism was analyzed in primary Fabry fibroblasts and α-Gal A knockout podocytes using targeted tandem liquid chromatography-mass spectrometry. Our findings establish lectins as a robust tool for improved diagnostics and research of Fabry disease and provide evidence of SL changes in cultured human cells, filling a knowledge gap. Full article

(This article belongs to the Section Biochemistry)

► Show Figures

Figure 1

16 pages, 4991 KiB

Open AccessArticle

Isolation and Functional Characterization of the MADS-Box Gene AGAMOUS-LIKE 24 in Rubber Dandelion (Taraxacum kok-saghyz Rodin)

by Yijiao Cai, Wei Yang, Jin Yue, Jiaqi Chen, Jianfeng Xing, Xue Yang, De Ye, Chaorong Tang and Hui Liu

Int. J. Mol. Sci. 2025, 26(5), 2271; https://doi.org/10.3390/ijms26052271 - 4 Mar 2025

Abstract

Rubber dandelion (Taraxacum kok-saghyz Rodin, TKS), also referred to as Russian dandelion, is one of the most promising natural rubber (NR)-producing plants that produce high-quality NR comparable to that from the Pará rubber tree (Hevea brasiliensis, Hb), currently the only [...] Read more.

Rubber dandelion (Taraxacum kok-saghyz Rodin, TKS), also referred to as Russian dandelion, is one of the most promising natural rubber (NR)-producing plants that produce high-quality NR comparable to that from the Pará rubber tree (Hevea brasiliensis, Hb), currently the only commercial source. It needs further breeding to improve the agricultural traits. However, little has been known about the genetic mechanisms underlying the regulation of floral induction and flower development in TKS, an important trait that remains to be improved for commercial production. The MADS-box gene AGAMOUS-LIKE 24 (AGL24) plays important roles in floral induction and flower development. As the first step in understanding its roles in TKS, this study isolated and characterized the AGL24-homologous gene TkAGL24 in TKS. The TkAGL24 gene had a 705 bp coding sequence (CDS) that encoded a protein of 234 amino acids containing the conserved classic MADS-box type II domain and K-box domain, sharing 55.32% protein sequence identity with the AtAGL24 protein from Arabidopsis. TkAGL24 was highly expressed in leaf, latex, root, and peduncle but rarely or not in mature flower. The TkAGL24 protein was located in the nucleus and cytoplasm and did not have transcription activation activity in yeast cells. The overexpression of TkAGL24 in Arabidopsis could promote flowering and cause the abnormal development of flowers, similar to other AGL24-homologous genes from other species. Furthermore, the overexpression of TkAGL24 in TKS also affected the development of ligulate flowers. These results suggested that the cloned TkAGL24 gene is functional and may play important roles in floral induction and flower development in TKS, providing an insight into the possibility for the further studies of its roles and application to breeding. Full article

(This article belongs to the Section Molecular Plant Sciences)

► Show Figures

Figure 1

14 pages, 280 KiB

Open AccessReview

Expansion of Splice-Switching Therapy with Antisense Oligonucleotides

by Yasuhiro Takeshima

Int. J. Mol. Sci. 2025, 26(5), 2270; https://doi.org/10.3390/ijms26052270 - 4 Mar 2025

Abstract

Since 2016, splice-switching therapy, in which splicing is controlled by antisense oligonucleotides, has been applied in clinical practice for spinal muscular atrophy and Duchenne muscular dystrophy. In the former disease, this therapy induces exon inclusion, while, in the latter, it induces exon skipping, [...] Read more.

Since 2016, splice-switching therapy, in which splicing is controlled by antisense oligonucleotides, has been applied in clinical practice for spinal muscular atrophy and Duchenne muscular dystrophy. In the former disease, this therapy induces exon inclusion, while, in the latter, it induces exon skipping, leading expression of functional proteins. Basic and clinical studies of splice-switching therapy for many monogenic diseases have now been conducted. The molecular mechanisms of splice-switching therapy include not only the induction of exon inclusion and skipping, but also the induction of pseudoexon skipping and suppression of splicing sites generated by mutations. In addition, therapies that alter protein function by regulating splicing are being investigated not only for monogenic diseases but also for non-monogenic ones such as cancer and immune-related disorders. It is expected that many of these basic studies will be translated into clinical applications. This review describes the current status of basic research and clinical applications of splice-switching therapy to promote the development of treatments for noncurable diseases. Full article

(This article belongs to the Special Issue Splice-Switching Antisense Oligonucleotides: 30 Years after Advocating Exon-Skipping Therapy for Duchenne Muscular Dystrophy)

16 pages, 875 KiB

Open AccessReview

Low-Dose Ionizing Radiation and Male Reproductive Immunity: Elucidating Subtle Modulations and Long-Term Health Implications

by Jiacheng Yin, Yifan Ye, Yuankai Gao, Qing Xu, Muzhe Su, Shengkui Sun, Wenhui Xu, Qian Fu, An Wang and Sumin Hu

Int. J. Mol. Sci. 2025, 26(5), 2269; https://doi.org/10.3390/ijms26052269 - 4 Mar 2025

Abstract

Low-dose ionizing radiation (LDIR) is a prevalent environmental factor with profound impacts on male reproductive health, particularly on the testicular immune microenvironment. This review examines the multifaceted effects of LDIR, emphasizing its ability to induce genotoxic stress, oxidative damage, and epigenetic modifications in [...] Read more.

Low-dose ionizing radiation (LDIR) is a prevalent environmental factor with profound impacts on male reproductive health, particularly on the testicular immune microenvironment. This review examines the multifaceted effects of LDIR, emphasizing its ability to induce genotoxic stress, oxidative damage, and epigenetic modifications in reproductive cells. These alterations compromise DNA repair, disrupt chromatin structure, and induce immune dysregulation. Immune cells such as macrophages, T cells, natural killer cells, and dendritic cells exhibit significant functional changes under LDIR exposure, destabilizing the immune privilege critical for normal spermatogenesis. The long-term health implications of LDIR include impaired sperm quality, reduced fertility, and transgenerational risks through heritable genomic instability. This review underscores the importance of exploring the mechanisms underlying immune dysregulation and developing effective protective strategies. While LDIR’s full impact on male reproductive health remains to be elucidated, addressing the gaps in our understanding of immune microenvironmental changes is crucial for mitigating its adverse effects and improving reproductive health outcomes. Full article

(This article belongs to the Section Molecular Immunology)

► Show Figures

Figure 1

21 pages, 984 KiB

Open AccessReview

Brain Disease-Modifying Effects of Radiofrequency as a Non-Contact Neuronal Stimulation Technology

by Shulei Sun, Junsoo Bok, Yongwoo Jang and Hyemyung Seo

Int. J. Mol. Sci. 2025, 26(5), 2268; https://doi.org/10.3390/ijms26052268 - 4 Mar 2025

Abstract

Non-invasive, non-contact, and painless methods of electrical stimulation to enhance neural function have been widely studied in recent years, particularly in the context of neurodegenerative diseases such as Alzheimer’s disease (AD) and related dementias, which cause cognitive decline and other neurological symptoms. Radiofrequency [...] Read more.

Non-invasive, non-contact, and painless methods of electrical stimulation to enhance neural function have been widely studied in recent years, particularly in the context of neurodegenerative diseases such as Alzheimer’s disease (AD) and related dementias, which cause cognitive decline and other neurological symptoms. Radiofrequency (RF), which is a rate of oscillation in the range of 3 kHz to 300 GHz (3 THz), has been suggested as one potential non-contact neuronal stimulation (NCNS) technique for improving brain function. A new type of electrical stimulation uses a radiofrequency electromagnetic field (RF-EMF). RF exposure has been shown to modulate neural stimulation and influence various brain activities in in vitro and in vivo models. Recent studies have explored the effects of RF-EMF on human physiology, particularly in areas such as brain activity, cognition, and sleep behavior. In this review, we summarize recent findings about the effects of non-contact stimulations in in vitro studies, in vivo animal models, and human clinical cases. Full article

(This article belongs to the Collection Feature Papers in “Molecular Biology”)

► Show Figures

Figure 1

22 pages, 3631 KiB

Open AccessArticle

Improving Atorvastatin Release from Polyelectrolyte Complex-Based Hydrogels Using Freeze-Drying: Formulation and Pharmaceutical Assessment of a Novel Delivery System for Oral Candidiasis Treatment

by Joanna Potaś-Stobiecka, Radosław Aleksander Wach, Bożena Rokita, Weronika Kaja Simonik, Magdalena Wróblewska, Karolina Borkowska, Silje Mork, Nataša Škalko-Basnet and Katarzyna Winnicka

Int. J. Mol. Sci. 2025, 26(5), 2267; https://doi.org/10.3390/ijms26052267 - 4 Mar 2025

Abstract

Atorvastatin calcium, an antifungal agent, has the potential to be repositioned/repurposed to combat the increasing antimicrobial resistance. However, one of the most crucial issues in developing atorvastatin calcium-loaded products with a topical antifungal effect is achieving the optimal release and dissolution rates of [...] Read more.

Atorvastatin calcium, an antifungal agent, has the potential to be repositioned/repurposed to combat the increasing antimicrobial resistance. However, one of the most crucial issues in developing atorvastatin calcium-loaded products with a topical antifungal effect is achieving the optimal release and dissolution rates of this statin to produce the desired therapeutic effect. In this paper, we report on the development and pharmaceutical assessment of hydrogels composed of low-molecular-weight chitosan, tragacanth, and xanthan gum/pectin/κ-carrageenan as potential drug carriers for atorvastatin calcium for buccal delivery. Multidirectional analysis of the carriers with regard to their drug-release profiles and mucoadhesive, antimicrobial, and cytotoxic properties was accompanied by an evaluation of the freeze-drying process used to improve the hydrogels’ applicability. Using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy techniques, the role of lyophilization in enhancing atorvastatin calcium delivery from polyelectrolyte complex-based matrices via drug amorphization was demonstrated. The freeze-dried hydrogels had significantly improved release and dissolution rates for the amorphic statin. Therefore, there is great potential for the use of lyophilization in the design of polyelectrolyte complex-based semi-solids in usable dosage forms for numerous crystalline and poorly water-soluble active substances. Full article

(This article belongs to the Special Issue Applications of Biomaterials in Drug Development)

► Show Figures

Figure 1

24 pages, 4006 KiB

Open AccessReview

Molecular Epidemiology of Streptococcus pneumoniae Serotype 1: A Systematic Review of Circulating Clones and Clonal Clusters

by Onyansaniba K. Ntim and Eric S. Donkor

Int. J. Mol. Sci. 2025, 26(5), 2266; https://doi.org/10.3390/ijms26052266 - 4 Mar 2025

Abstract

Streptococcus pneumoniae serotype 1 is one of the most prevalent serotypes commonly associated with invasive pneumococcal disease cases and outbreaks worldwide. Several sequence types of this serotype have been identified globally, including those exhibiting both high virulence potential and antimicrobial resistance profiles. This [...] Read more.

Streptococcus pneumoniae serotype 1 is one of the most prevalent serotypes commonly associated with invasive pneumococcal disease cases and outbreaks worldwide. Several sequence types of this serotype have been identified globally, including those exhibiting both high virulence potential and antimicrobial resistance profiles. This systematic review presents the global distribution of clones of pneumococcal serotype 1, describing their circulating patterns in various regions in the world. A database search was conducted in Google Scholar, PubMed, Scopus, ScienceDirect, and Web of Science using keywords related to Streptococcus pneumoniae serotype 1. The inclusion criteria entailed peer-reviewed studies published in English describing the utilization of at least one molecular genotyping tool to identify S. pneumoniae serotype 1 clones based on their sequence types. Data extracted were managed and analyzed using Microsoft Excel 365 (Version 2108). Forty-three studies were finally included in the systematic review. A total of 103 MLST serotype 1 sequence types were identified in 48 countries. These clones were widely reported to be associated with invasive pneumococcal diseases. Globally, ST217 and ST306 clonal complexes (CC217 and CC306) were the predominant lineages of serotype 1 sequence types, exhibiting distinct continental distribution patterns. CC217, characterized by ST217, ST303, ST612, ST618, and ST3081, was predominant in Africa and Asia. ST306 clonal complex, which is grouped into ST306, ST304, and ST227 were mostly found in Europe, Oceania, North America, and some countries in South America. ST615 was predominant in Chile, Peru, and Argentina. The hypervirulence nature of serotype 1, coupled with its complex genetic diversity, poses a significant public health threat. Our findings emphasize the need for enhanced surveillance and targeted interventions to mitigate the spread of these hypervirulent clones, ultimately informing evidence-based strategies for disease prevention and control. Full article

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

► Show Figures

Figure 1

21 pages, 5172 KiB

Open AccessArticle

Characterizing the Ovarian Cytogenetic Dynamics of Sichuan Bream (Sinibrama taeniatus) During Vitellogenesis at a Single-Cell Resolution

by Zhe Zhao, Shixia Huang, Qilin Feng, Li Peng, Qiang Zhao and Zhijian Wang

Int. J. Mol. Sci. 2025, 26(5), 2265; https://doi.org/10.3390/ijms26052265 - 4 Mar 2025

Abstract

Vitellogenesis in fish represents a critical phase of oogenesis, significantly influencing the nutritional provisioning for oocyte maturation and subsequent offspring development. However, research on the physiological mechanisms governing vitellogenesis at the single-cell level remains limited. In this study, we performed single-nucleus RNA sequencing [...] Read more.

Vitellogenesis in fish represents a critical phase of oogenesis, significantly influencing the nutritional provisioning for oocyte maturation and subsequent offspring development. However, research on the physiological mechanisms governing vitellogenesis at the single-cell level remains limited. In this study, we performed single-nucleus RNA sequencing (snRNA-seq) on the ovaries of Sichuan bream (Sinibrama taeniatus). We first identified six distinct cell types (germ cells, follicular cells, immune cells, stromal cells, endothelial cells, and epithelial cells) in the ovaries based on typical functional marker genes. Subsequently, we reconstructed the developmental trajectory of germ cells using pseudotime analysis, which describes the transcriptional dynamics of germ cells at various developmental stages. Additionally, we identified transcription factors (TFs) specific to germ cells that exhibit high activity at each developmental stage. Furthermore, we analyzed the genetic functional heterogeneity of germ cells and follicular cells at different developmental stages to elucidate their contributions to vitellogenesis. Finally, cell interaction analysis revealed that germ cells communicate with somatic cells or with each other via multiple receptors and ligands to regulate growth, development, and yolk acquisition. These findings enhance our understanding of the physiological mechanisms underlying vitellogenesis in fish, providing a theoretical foundation for regulating ovarian development in farmed fish. Full article

(This article belongs to the Special Issue Omics Era: From Principles to Applications in Disease Diagnosis and Treatment)

► Show Figures

Figure 1

Journal Description

International Journal of Molecular Sciences

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI