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Biomolecules
Volume 15
Issue 7
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Biomolecules, Volume 15, Issue 7 (July 2025) – 144 articles

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11 pages, 520 KiB  
Article
Hemodynamic and Morpho-Biochemical Parameters of Rabbit Blood After Injection of Enzyme Preparations
by V. G. Vertiprakhov, N. A. Sergeenkova, S. V. Karamushkina and B. Sh. Dashieva
Biomolecules 2025, 15(7), 1049; https://doi.org/10.3390/biom15071049 - 18 Jul 2025
Abstract
The anti-inflammatory effect of trypsin in animals and humans is the basis for the development of new veterinary and medical drugs and alternatives to antibiotics. The current experiment analyzed the effect of pig pancreatic tissue lyophilizate and crystalline trypsin on the hemodynamic and [...] Read more.
The anti-inflammatory effect of trypsin in animals and humans is the basis for the development of new veterinary and medical drugs and alternatives to antibiotics. The current experiment analyzed the effect of pig pancreatic tissue lyophilizate and crystalline trypsin on the hemodynamic and morpho-biochemical parameters of rabbit blood. The experiments were carried out on 20 rabbits of the Soviet chinchilla breed of 6–8 months of age. Animals were intramuscularly injected with sterile solution of 0.9% NaCl in 0.5 mL (group 1, n = 5), sterile solution of crystalline trypsin in 0.9% NaCl at a concentration of 0.25 mg/kg body weight (group 2, n = 5), sterile solution of crystalline trypsin in 0, 9% NaCl at a concentration of 0.5 mg/kg body weight (group 3, n = 5), or sterile suspension of pig pancreas lyophilizate at a concentration of 1 mg/kg body weight (group 4, n = 5). Animals were injected once daily for five consecutive days. Significant changes in arterial blood pressure, serum enzymes activity, and the count of various blood cellular components were induced by the administration of different trypsin preparations. All data obtained indicate the presence of a biologically active substance in the lyophilizate, the effect of which requires further animal studies to create a prototype for the development of new drugs for human and animal use. Full article
(This article belongs to the Special Issue Digestive Enzymes in Health and Disease)
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19 pages, 2093 KiB  
Review
PHF20L1: An Epigenetic Regulator in Cancer and Beyond
by Yishan Wang, Qin Hu, Haixia Zhao, Lulu Zeng, Zhongwei Zhao, Xia Li, Qiaoyou Weng, Yang Yang, Minjiang Chen, Jiansong Ji and Rongfang Qiu
Biomolecules 2025, 15(7), 1048; https://doi.org/10.3390/biom15071048 - 18 Jul 2025
Abstract
Plant homeodomain (PHD) finger protein 20-like 1 (PHF20L1) is a novel epigenetic “reader” that specifically recognises histone post-translational modifications (PTMs) via its Tudor and PHD finger domains, thereby regulating chromatin remodelling, DNA damage repair, and oncogene transcriptional activation. This review comprehensively summarises the [...] Read more.
Plant homeodomain (PHD) finger protein 20-like 1 (PHF20L1) is a novel epigenetic “reader” that specifically recognises histone post-translational modifications (PTMs) via its Tudor and PHD finger domains, thereby regulating chromatin remodelling, DNA damage repair, and oncogene transcriptional activation. This review comprehensively summarises the role of PHF20L1 in various cancers, including breast, ovarian, and colorectal cancers, as well as retinoblastomas, and elucidates its molecular mechanisms of action in cancer pathogenesis. Accumulating evidence indicates that PHF20L1 is upregulated in these malignancies and drives tumour progression by promoting proliferation, metastasis, and immune evasion. Furthermore, PHF20L1 orchestrates tumour-related gene expression by interacting with key epigenetic complexes. Given its unique structural features, we propose novel strategies for developing small-molecule inhibitors and combinatorial therapies, providing a theoretical basis for targeted epigenetic regulation for precision treatment. Future research should further investigate the molecular regulatory networks of PHF20L1 in different cancers and other human diseases and focus on developing specific small-molecule inhibitors to enable precision-targeted therapies. Full article
(This article belongs to the Special Issue Tumor Genomics and Liquid Biopsy in Cancer Biology)
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15 pages, 1142 KiB  
Article
The Estimated Intake of S100B Relates to Microbiota Biodiversity in Different Diets
by Tehreema Ghaffar, Veronica Volpini, Serena Platania, Olga Vassioukovitch, Alessandra Valle, Federica Valeriani, Fabrizio Michetti and Vincenzo Romano Spica
Biomolecules 2025, 15(7), 1047; https://doi.org/10.3390/biom15071047 - 18 Jul 2025
Abstract
The S100B protein, known for its role in the central and enteric nervous systems, has recently been identified in dietary sources such as milk, dairy products, fruits, and vegetables. Given its potential interaction with the gut microbiota, this study explores the relationship between [...] Read more.
The S100B protein, known for its role in the central and enteric nervous systems, has recently been identified in dietary sources such as milk, dairy products, fruits, and vegetables. Given its potential interaction with the gut microbiota, this study explores the relationship between dietary intake of S100B and microbiota biodiversity across different diets. A comprehensive study was conducted, estimating S100B concentrations in 13 dietary patterns recommended in different countries. This is the first study to provide a comparative estimation of S100B exposure from the diet and to explore its potential ecological and epidemiological relevance. The association between S100B levels and microbiota biodiversity was statistically analyzed, showing a direct correlation. Microbial diversity was assessed using the Shannon index, based on data extracted from studies reporting microbiota composition across dietary patterns. Additionally, the relative risk of Crohn’s disease was assessed in different populations to examine potential links between dietary patterns, S100B, and chronic disease prevention. A moderate positive correlation (R2 = 0.537) was found between S100B concentration and Shannon index, suggesting that diets higher in S100B (e.g., Mediterranean diet) were associated with higher microbial alpha-diversity. Furthermore, Western-style diets, with the lowest S100B levels, exhibited a higher relative risk for Crohn’s disease (R2 = 0.780). These findings highlight the potential role of dietary S100B content in modulating gut microbiota diversity and reducing chronic disease risk. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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16 pages, 5016 KiB  
Article
BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma
by Mercedes Olvera-Valencia, Fernando Luna-Maldonado, Joselyn Juarez-Reyes, Alejandro Lopez-Saavedra, Jossimar Coronel-Hernandez, Oliver Millan-Catalan, Daniel Guzman-Gomez, Frida Rodríguez-Izquierdo, Luis A. Herrera, David Francisco Cantú-De León, Carlos Perez-Plasencia and Eloy-Andres Pérez-Yepez
Biomolecules 2025, 15(7), 1046; https://doi.org/10.3390/biom15071046 - 18 Jul 2025
Abstract
Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A [...] Read more.
Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, BUB1 was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high BUB1 expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas. Full article
(This article belongs to the Special Issue Signaling Pathways as Therapeutic Targets for Cancer)
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29 pages, 3654 KiB  
Review
A Mechanistic Approach to Replacing Antibiotics with Natural Products in the Treatment of Bacterial Diarrhea
by Mingbang Wei, Huaizhi Liu, Zhefan Hu, Peixiao Wen, Yourong Ye, Yangzom Chamba, Hongliang Zhang and Peng Shang
Biomolecules 2025, 15(7), 1045; https://doi.org/10.3390/biom15071045 - 18 Jul 2025
Abstract
Natural products have emerged as potential alternatives to antibiotics in the treatment of bacterial diarrhea, due to their multi-targeting effects, low potential for inducing resistance, and favorable safety profiles. Currently, the search for natural product-based therapies has become an emerging focus in medical [...] Read more.
Natural products have emerged as potential alternatives to antibiotics in the treatment of bacterial diarrhea, due to their multi-targeting effects, low potential for inducing resistance, and favorable safety profiles. Currently, the search for natural product-based therapies has become an emerging focus in medical research. This growing interest is driven by the increasing awareness that the widespread and irrational use of antibiotics has contributed to the alarming rise in antibiotic-resistant bacterial strains, which in turn diminishes the efficacy of conventional drugs. Among these concerns, the limitations of antibiotics in managing bacterial diarrhea and the potential mechanisms by which natural products exert therapeutic effects are the main focus of this paper. Natural products, containing a wide array of bioactive compounds, can not only directly inhibit the growth of pathogenic bacteria, disrupt bacterial membrane synthesis, and reduce toxin production, but also modulate inflammatory responses, enhance immune function, repair intestinal barriers, and restore gut microbial ecology—highlighting their systemic and multi-targeted therapeutic potential. Therefore, this paper will elaborate on how natural products combat bacterial diarrhea from three aspects: the pathogen and pathogenesis of bacterial diarrhea, natural product-based therapeutic studies, and the underlying mechanisms of action, thereby proposing natural products as viable alternatives to antibiotics. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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17 pages, 1772 KiB  
Article
Exploration of the Possible Relationships Between Gut and Hypothalamic Inflammation and Allopregnanolone: Preclinical Findings in a Post-Finasteride Rat Model
by Silvia Diviccaro, Roberto Oleari, Federica Amoruso, Fabrizio Fontana, Lucia Cioffi, Gabriela Chrostek, Vera Abenante, Jacopo Troisi, Anna Cariboni, Silvia Giatti and Roberto Cosimo Melcangi
Biomolecules 2025, 15(7), 1044; https://doi.org/10.3390/biom15071044 - 18 Jul 2025
Abstract
Background: Finasteride, a 5α-reductase inhibitor commonly prescribed for androgenetic alopecia, has been linked to persistent adverse effects after discontinuation, known as post-finasteride syndrome (PFS). Symptoms include neurological, psychiatric, sexual, and gastrointestinal disturbances. Emerging evidence suggests that PFS may involve disruption of sex steroid [...] Read more.
Background: Finasteride, a 5α-reductase inhibitor commonly prescribed for androgenetic alopecia, has been linked to persistent adverse effects after discontinuation, known as post-finasteride syndrome (PFS). Symptoms include neurological, psychiatric, sexual, and gastrointestinal disturbances. Emerging evidence suggests that PFS may involve disruption of sex steroid homeostasis, neuroactive steroid deficiency (notably allopregnanolone, ALLO), and gut–brain axis alterations. Objective: This study aimed to investigate the effects of finasteride withdrawal (FW) in a rat model and evaluate the potential protective effects of ALLO on gut and hypothalamic inflammation. Methods: Adult male Sprague Dawley rats were treated with finasteride for 20 days, followed by one month of drug withdrawal. A subgroup received ALLO treatment during the withdrawal. Histological, molecular, and biochemical analyses were performed on the colon and hypothalamus. Gut microbiota-derived metabolites and markers of neuroinflammation and blood–brain barrier (BBB) integrity were also assessed. Results: At FW, rats exhibited significant colonic inflammation, including a 4.3-fold increase in Mφ1 levels (p < 0.001), a 2.31-fold decrease in butyrate concentration (p < 0.01), and elevated hypothalamic GFAP and Iba-1 protein expression (+360%, p < 0.01 and +100%, p < 0.01, respectively). ALLO treatment rescued these parameters in both the colon and hypothalamus but only partially restored mucosal and BBB structural integrity, as well as the NF-κB/PPARγ pathway. Conclusions: This preclinical study shows that FW causes inflammation in both the gut and hypothalamus in rats. ALLO treatment helped reduce several of these effects. These results suggest ALLO could have a protective role and have potential as a treatment for PFS patients. Full article
(This article belongs to the Section Molecular Medicine)
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28 pages, 1119 KiB  
Review
β-Catenin: A Key Molecule in Osteoblast Differentiation
by Edyta Wróbel, Piotr Wojdasiewicz, Agnieszka Mikulska and Dariusz Szukiewicz
Biomolecules 2025, 15(7), 1043; https://doi.org/10.3390/biom15071043 - 18 Jul 2025
Abstract
β-catenin is a key regulator of osteoblast differentiation, proliferation, and bone homeostasis. Through its interaction with transcription factors such as TCF/LEF, Runx2, and Osx, it coordinates gene expression essential for osteogenesis. The aim of this review is to demonstrate how β-catenin signaling is [...] Read more.
β-catenin is a key regulator of osteoblast differentiation, proliferation, and bone homeostasis. Through its interaction with transcription factors such as TCF/LEF, Runx2, and Osx, it coordinates gene expression essential for osteogenesis. The aim of this review is to demonstrate how β-catenin signaling is modulated by various physiological and pathological factors, including mechanical loading, oxidative stress, HIV-1 gp120, fluoride, implant topography, and microRNAs. These factors influence Wnt/β-catenin signaling through different mechanisms, often exerting opposing effects on osteoblast function. By integrating these modulators, we provide a comprehensive view of the dynamic regulation of β-catenin in bone biology. Understanding this complexity may provide insight into novel therapeutic strategies targeting β-catenin in bone regeneration, metabolic bone diseases, and pathologies such as HIV-associated bone loss or osteosarcoma. Full article
(This article belongs to the Section Molecular Biology)
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13 pages, 726 KiB  
Article
Bilirubin Metabolism and Thyroid Cancer: Insights from ALBI and PALBI Indices
by Jong Won Shin, Jae Woong Sull, Nguyen Thien Minh and Sun Ha Jee
Biomolecules 2025, 15(7), 1042; https://doi.org/10.3390/biom15071042 - 18 Jul 2025
Abstract
Background: This study evaluated the association between bilirubin subtypes (total, indirect, and direct bilirubin) and thyroid cancer risk, with a particular focus on stratified analyses using the ALBI (Albumin-Bilirubin) and PALBI (Platelet-Albumin-Bilirubin) indices by sex, smoking and drinking status, and age under 50 [...] Read more.
Background: This study evaluated the association between bilirubin subtypes (total, indirect, and direct bilirubin) and thyroid cancer risk, with a particular focus on stratified analyses using the ALBI (Albumin-Bilirubin) and PALBI (Platelet-Albumin-Bilirubin) indices by sex, smoking and drinking status, and age under 50 years. Methods: Data were obtained from 133,596 participants in the Korean Cancer Prevention Study-II (KCPS-II) cohort. During a mean follow-up period of 13.55 years, 2314 cases of thyroid cancer (ICD-10: C73) were identified. Serum bilirubin levels and ALBI and PALBI indices were analyzed using Cox proportional hazards regression models stratified by age, sex, smoking, and alcohol consumption status to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In women, indirect bilirubin showed the strongest inverse association with thyroid cancer risk. ALBI and PALBI indices based on indirect bilirubin also demonstrated significant associations. A 1 standard deviation (SD) increase in indirect bilirubin was associated with a decreased risk of thyroid cancer (HR: 0.92, 95% CI: 0.84–0.99), and the ALBI index similarly showed an inverse association (HR: 0.92, 95% CI: 0.87–0.99). In contrast, the PALBI index was positively associated with thyroid cancer risk (HR: 1.11, 95% CI: 1.03–1.20). Among women who had never smoked, significant associations were observed for indirect bilirubin (HR: 0.91, 95% CI: 0.83–1.00), ALBI (HR: 0.93, 95% CI: 0.86–1.00), and PALBI (HR: 1.14, 95% CI: 1.05–1.23). In analyses stratified by alcohol consumption, the PALBI index was associated with increased thyroid cancer risk in non-drinkers, former drinkers, and ever drinkers, with respective risk increases of 15%, 18%, and 9%. Conclusions: In women, indirect bilirubin was significantly and inversely associated with thyroid cancer risk, and the ALBI and PALBI indices incorporating indirect bilirubin showed consistent results. These findings suggest that indirect bilirubin may play a critical role in the metabolic pathways underlying thyroid cancer in women. Full article
(This article belongs to the Special Issue Molecular Basis and Oxidative Stress of Thyroid Diseases)
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16 pages, 810 KiB  
Review
Synergizing Liquid Biopsy and Hybrid PET Imaging for Prognostic Assessment in Prostate Cancer: A Focus Review
by Federica Stracuzzi, Sara Dall’ Armellina, Gayane Aghakhanyan, Salvatore C. Fanni, Giacomo Aringhieri, Lorenzo Faggioni, Emanuele Neri, Duccio Volterrani and Dania Cioni
Biomolecules 2025, 15(7), 1041; https://doi.org/10.3390/biom15071041 - 18 Jul 2025
Abstract
Positron emission tomography (PET) and liquid biopsy have independently transformed prostate cancer management. This systematic review explores the complementary roles of PET imaging and liquid biopsy in prostate cancer, focusing on their combined diagnostic, monitoring, and prognostic potential. A systematic search of PubMed, [...] Read more.
Positron emission tomography (PET) and liquid biopsy have independently transformed prostate cancer management. This systematic review explores the complementary roles of PET imaging and liquid biopsy in prostate cancer, focusing on their combined diagnostic, monitoring, and prognostic potential. A systematic search of PubMed, Scopus, and Cochrane Library databases was conducted to identify human studies published in English up to January 2025. Seventeen studies met the inclusion criteria and were analyzed according to PRISMA guidelines. Across the included studies, PET-derived imaging metrics, such as metabolic activity and radiotracer uptake, correlated consistently with liquid biopsy biomarkers, including circulating tumor cells and cell-free DNA. Their joint application demonstrated added value in early detection, treatment monitoring, and outcome prediction, particularly in castration-resistant prostate cancer. Independent and synergistic prognostic value was noted for both modalities, including survival outcomes such as overall survival and progression-free survival. Combining PET imaging and liquid biopsy emerges as a promising, non-invasive strategy for improving prostate cancer diagnosis, monitoring, and therapeutic stratification. While preliminary findings are encouraging, large-scale prospective studies are essential to validate their integrated clinical utility. Full article
(This article belongs to the Special Issue Spotlight on Hot Cancer Biological Biomarkers)
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14 pages, 4042 KiB  
Article
Conditional Deletion of Translin/Trax in Dopaminergic Neurons Reveals No Impact on Psychostimulant Behaviors or Adiposity
by Yunlong Liu, Renkun Wu, Gaiyuan Geng, Helian Yang, Chunmiao Wang, Mengtian Ren and Xiuping Fu
Biomolecules 2025, 15(7), 1040; https://doi.org/10.3390/biom15071040 - 17 Jul 2025
Viewed by 46
Abstract
Despite the abundant expression of the microRNA-degrading Translin (TN)/Trax (TX) complex in midbrain dopaminergic (DA) neurons and its implication in neuropsychiatric disorders, its cell-autonomous roles in metabolic and behavioral responses remain unclear. To address this, we generated DA neuron-specific conditional knockout (cKO) mice [...] Read more.
Despite the abundant expression of the microRNA-degrading Translin (TN)/Trax (TX) complex in midbrain dopaminergic (DA) neurons and its implication in neuropsychiatric disorders, its cell-autonomous roles in metabolic and behavioral responses remain unclear. To address this, we generated DA neuron-specific conditional knockout (cKO) mice for Tsn (TN) or Tsnax (TX) using DAT-Cre. Immunostaining confirmed efficient TX loss in Tsnax cKO DA neurons without affecting TN, while Tsn deletion abolished TX expression, revealing asymmetric protein dependency. Body composition analysis showed no alterations in adiposity in either cKO model. Locomotor responses to acute or repeated administration of cocaine (20 mg/kg) or amphetamine (2.5 mg/kg) were unchanged in Tsn or Tsnax cKO mice. Furthermore, amphetamine-induced conditioned place preference (1 mg/kg) was unaffected. These results demonstrate that the TN/TX complex within DA neurons is dispensable for regulating adiposity, psychostimulant-induced locomotion (both acute and sensitized), or amphetamine reward-related behavior, suggesting its critical functions may lie outside these specific domains. Full article
(This article belongs to the Section Molecular Genetics)
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14 pages, 3379 KiB  
Article
Effects of Isaria cateniannulata and Beauveria bassiana on Buckwheat Growth and Associated Insect Pest
by Xiaona Zhang, Lingdi Gu, Can Liu, Guimin Yang, Xue Yang, Kaifeng Huang and Qingfu Chen
Biomolecules 2025, 15(7), 1039; https://doi.org/10.3390/biom15071039 - 17 Jul 2025
Viewed by 45
Abstract
The Tetranychus urticae Koch (Acari: Tetranychidae) is one of the primary pests affecting buckwheat, and its management has become increasingly critical. Entomopathogenic fungi offer a promising way to solve this problem by providing both pest control and disease resistance, as well as promoting [...] Read more.
The Tetranychus urticae Koch (Acari: Tetranychidae) is one of the primary pests affecting buckwheat, and its management has become increasingly critical. Entomopathogenic fungi offer a promising way to solve this problem by providing both pest control and disease resistance, as well as promoting plant growth through endophytic colonization. This study investigated the effects of applying Isaria cateniannulata (Liang) Samson & Hywel-Jones and Beauveria bassiana (Bals.-Criv.) Vuill. on different buckwheat varieties, and analyzed the physiological indices of buckwheat, the population of T. urticae and Euseius nicholsi (Ehara & Lee). Results showed that the optimum concentration for fungal colonization on buckwheat was 1 × 107 spores/mL. The combined application of I. cateniannulata and B. bassiana significantly enhanced buckwheat growth, with root length, plant height, main stem diameter, fresh weight, and dry weight reaching 63.3 mm, 24.1 cm, 2.1 mm, 2.0 g, and 0.1 g, respectively. The highest escape rate of T. urticae was 76.33%. Furthermore, the combined application of mixed fungal suspension and E. nicholsi had the best control effect on T. urticae, with pest suppression exceeding 97.83% and an oviposition as low as 0.25 eggs per female. This study is the first to demonstrate that the joint application of I. cateniannulata and B. bassiana can promote buckwheat growth and, when combined with predatory mites, effectively control T. urticae. These findings provide a theoretical basis for the development of integrated biocontrol strategies combining entomopathogenic fungi and predatory mites. Full article
(This article belongs to the Special Issue Microbial Biocontrol and Plant-Microbe Interactions)
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30 pages, 1348 KiB  
Review
Emerging Molecular Mechanisms in Malaria Pathogenesis and Novel Therapeutic Approaches: A Focus on P. falciparum Malaria
by Adekunle Sanyaolu, Aleksandra Marinkovic, Stephanie Prakash, Vyshnavy Balendra, Omar Shazley, Tatiana Gardellini, Abdul Jan, Kokab Younis, Chuku Okorie and Ricardo Izurieta
Biomolecules 2025, 15(7), 1038; https://doi.org/10.3390/biom15071038 - 17 Jul 2025
Viewed by 76
Abstract
Malaria is still one of the biggest global health problems, especially in parts of the world, such as sub-Saharan Africa, which remains most heavily affected. Despite significant advancements in testing, treatment, and prevention, malaria continues to seriously impact millions, primarily young children and [...] Read more.
Malaria is still one of the biggest global health problems, especially in parts of the world, such as sub-Saharan Africa, which remains most heavily affected. Despite significant advancements in testing, treatment, and prevention, malaria continues to seriously impact millions, primarily young children and populations in rural and impoverished areas. This paper looks at how the malaria parasite works inside the body, how it avoids the immune system, and how it becomes resistant to current drugs. Thanks to new advances in genetic and biochemical research, scientists are discovering new weak points in the parasite that could lead to better treatments. New vaccines, like RTS, S and R21, along with antibody-based therapies, offer renewed hope; however, extending the duration of the immunity they induce and ensuring effectiveness across diverse parasite strains remain significant challenges. Solving the malaria crisis will require more than science—it also necessitates equitable and timely access to treatments, robust health systems, and international collaboration. Continued research and global cooperation bring the world closer to ending malaria for good. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms and Therapeutics for Malaria)
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27 pages, 7011 KiB  
Review
Conceptus Elongation, Implantation, and Early Placental Development in Species with Central Implantation: Pigs, Sheep, and Cows
by Gregory A. Johnson, Thainá Minela, Heewon Seo, Fuller W. Bazer, Robert C. Burghardt, Guoyao Wu, Ky G. Pohler, Claire Stenhouse, Joe W. Cain, Zachary K. Seekford and Dallas R. Soffa
Biomolecules 2025, 15(7), 1037; https://doi.org/10.3390/biom15071037 - 17 Jul 2025
Viewed by 42
Abstract
Species have different strategies for implantation and placentation. Much can be learned about general molecular and cellular biology through the examination and comparison of these differences. To varying degrees, implantation in all species includes alterations in epithelial polarity, the transformation of the endometrial [...] Read more.
Species have different strategies for implantation and placentation. Much can be learned about general molecular and cellular biology through the examination and comparison of these differences. To varying degrees, implantation in all species includes alterations in epithelial polarity, the transformation of the endometrial stroma, the differentiation of the trophoblast, cell-to-cell and tissue-to-tissue signaling through hormones, cytokines, and extracellular vesicles, and the alteration of the maternal immune system. This review focuses on implantation in pigs, sheep, and cows. These species share with mice/rats and humans/primates the key events of early embryonic development, pregnancy recognition, and the establishment of functional placentation. However, there are differences between the pregnancies of livestock and other species that make livestock unique biomedical models for the study of pregnancy and cell biology in general. Pig, sheep, and cow conceptuses (embryo/fetus and associated placental membranes) elongate prior to implantation, displaying central implantation, extended periods of conceptus attachment to the uterus, and epitheliochorial (pigs) and synepitheliochorial (sheep and cows) placentation. This review will discuss what is understood about how the trophoblast and extraembryonic endoderm of pig, sheep, and cow conceptuses elongate, and how a major goal of current in vitro models is to achieve conceptus elongation. It will then examine the adhesion cascade for conceptus implantation that initiates early placental development in pigs, sheep, and cows. Finally, it will conclude with a brief overview of early placental development in pigs, sheep, and cows, with a listing of some important “omics” studies that have been published. Full article
(This article belongs to the Special Issue Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling)
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19 pages, 2563 KiB  
Review
The Intricate Process of Calcification in Granuloma Formation and the Complications Following M. tuberculosis Infection
by Nickolas Yedgarian, Jacqueline Agopian, Brandon Flaig, Fouad Hajjar, Arshavir Karapetyan, Kannan Murthy, Ani Patrikyan, Kirakos Tomas, Kevin Tumanyan, Mohammad J. Nasiri, Selvakumar Subbian and Vishwanath Venketaraman
Biomolecules 2025, 15(7), 1036; https://doi.org/10.3390/biom15071036 - 17 Jul 2025
Viewed by 55
Abstract
Mycobacterium tuberculosis—an acid-fast staining bacterium—is a serious global health challenge that can have both short-term and long-term complications. Although the immune response helps trap the infection, it can also cause necrosis and calcification, leading to lung tissue damage. Calcification is a known [...] Read more.
Mycobacterium tuberculosis—an acid-fast staining bacterium—is a serious global health challenge that can have both short-term and long-term complications. Although the immune response helps trap the infection, it can also cause necrosis and calcification, leading to lung tissue damage. Calcification is a known outcome of chronic granuloma evolution in TB. Multiple pathways contribute to fibrosis and calcification; some examples are IL-1β, TGF-β, and TNF-α. Current antifibrotic drugs, such as nintedanib and pirfenidone, are effective but may increase the risk of latent tuberculosis reactivation in certain patients. Experimental therapies such as artemisinin derivatives have shown promise in preclinical TB fibrosis models, while cell-based therapies like bone marrow-derived mononuclear cells are also under early investigation for dual antifibrotic and immunomodulatory effects. This literature review will explore recent studies on the pathogenesis of M. tuberculosis, the mechanisms underlying calcification in granuloma formation, and subsequent complications of the disease process. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Infectious Pathogen Adaptation, Emergence, and Re-emergence)
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18 pages, 7149 KiB  
Article
Co-Inhibition of PARP and STAT3 as a Promising Approach for Triple-Negative Breast Cancer
by Changyou Shi, Li Pan, Satomi Amano, Mei-Yi Wu, Chenglong Li and Jiayuh Lin
Biomolecules 2025, 15(7), 1035; https://doi.org/10.3390/biom15071035 - 17 Jul 2025
Viewed by 62
Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive subtype known for its rapid metastatic potential. Despite its severity, treatment options for TNBC remain limited. Olaparib, an FDA-approved PARP inhibitor, has been used to treat germline BRCA-mutated TNBC in both metastatic and high-risk [...] Read more.
Triple-negative breast cancer (TNBC) is a highly aggressive subtype known for its rapid metastatic potential. Despite its severity, treatment options for TNBC remain limited. Olaparib, an FDA-approved PARP inhibitor, has been used to treat germline BRCA-mutated TNBC in both metastatic and high-risk early-stage settings. However, acquired resistance to PARP inhibitors and their limited applicability in non-BRCA TNBCs are now two major growing clinical problems. Activation of the IL-6/STAT3 signaling cascade has been implicated in therapeutic resistance. In this study, we evaluated the combined effects of the PARP inhibitor olaparib and the STAT3 inhibitor LLL12B in human TNBC cell lines with both BRCA mutations and wild-type BRCA status. Our results demonstrate that the PARP inhibitor olaparib can induce increased interleukin-6 (IL-6) in TNBC cells, with ELISA showing a 2- to 39-fold increase across five cell lines. MTT assays revealed that knocking down or inhibiting STAT3, a key downstream effector of the IL-6/GP130 pathway, sensitizes TNBC cells to olaparib. Treatment with either olaparib or LLL12B alone reduced TNBC cell viability, migration, and invasion. Notably, their combined administration produced a markedly enhanced inhibitory effect compared to individual treatments, regardless of BRCA mutation status. These findings highlight the potential of dual PARP and STAT3 inhibition as a novel targeted therapeutic strategy for both BRCA-mutant and BRCA-proficient TNBC. Full article
(This article belongs to the Special Issue PARPs in Cell Death and PARP Inhibitors in Cancers: 2nd Edition)
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16 pages, 805 KiB  
Review
Heparin, Heparin-like Molecules, and Heparin Mimetics in Breast Cancer: A Concise Review
by Diego R. Gatica Portillo, Yishu Li, Navneet Goyal, Brian G. Rowan, Rami A. Al-Horani and Muralidharan Anbalagan
Biomolecules 2025, 15(7), 1034; https://doi.org/10.3390/biom15071034 - 17 Jul 2025
Viewed by 88
Abstract
Heparin and heparan sulfate are essential in various biological processes relevant to cancer biology and pathology. Given the clinical importance of breast cancer, it is of high interest to seek more effective and safer treatment. The application of heparins (UFH, LMWH, ULMWH, fondaparinux) [...] Read more.
Heparin and heparan sulfate are essential in various biological processes relevant to cancer biology and pathology. Given the clinical importance of breast cancer, it is of high interest to seek more effective and safer treatment. The application of heparins (UFH, LMWH, ULMWH, fondaparinux) and heparin mimetics as potential treatments is particularly interesting. Their use led to promising results in various breast cancer models by exhibiting anti-angiogenic and anti-metastatic properties. This article concisely reviews studies involving heparins and mimetics in both in vitro and in vivo breast cancer settings. We highlight molecules, conjugates, delivery systems, and combinations involving heparin or its mimetics. We also survey several potential biological targets such as VEGF, FGF-2, TGFβ-1, PDGF-B, NPP-1, CXCL12-CXCR4 axis, and CCR7-CCL21 axis. Overall, heparins and their mimetics, conjugates, and combinations represent a powerful strategy to effectively and safely treat breast cancer, which is the most common cancer diagnosed in women worldwide and the fifth leading cause of cancer-related deaths worldwide. Full article
(This article belongs to the Special Issue Advances in Glycosaminoglycans (GAGs) and Mimetics)
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13 pages, 2208 KiB  
Article
Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone
by Tamara Timic Stamenic, Ian Coulter, Douglas F. Covey and Slobodan M. Todorovic
Biomolecules 2025, 15(7), 1033; https://doi.org/10.3390/biom15071033 - 17 Jul 2025
Viewed by 115
Abstract
Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone [...] Read more.
Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone (EpiP) in wild-type mice using behavioral assessment of hypnosis (loss of righting reflex, LORR) and in vivo electrophysiological recordings. Specifically, local field potentials (LFPs) were recorded from the central medial thalamus (CMT) and electroencephalogram (EEG) signals were recorded from the barrel cortex. We found that EpiP-induced LORR exhibited clear sex differences, with females showing increased sensitivity. Spectral power analysis and thalamocortical (TC) and corticocortical (CC) phase synchronization further supported enhanced hypnotic susceptibility in female mice. Our findings reveal characteristic sex-dependent effects of EpiP on the synchronized electrical activity in both thalamus and cortex. These results support renewed exploration of endogenous NAS as clinically relevant anesthetic agents. Full article
(This article belongs to the Special Issue Role of Neuroactive Steroids in Health and Disease: 2nd Edition)
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21 pages, 4209 KiB  
Article
The Upregulation of L1CAM by SVHRSP Mitigates Neuron Damage, Spontaneous Seizures, and Cognitive Dysfunction in a Kainic Acid-Induced Rat Model of Epilepsy
by Zhen Li, Biying Ge, Haoqi Li, Chunyao Huang, Yunhan Ji, Melitta Schachner, Shengming Yin, Sheng Li and Jie Zhao
Biomolecules 2025, 15(7), 1032; https://doi.org/10.3390/biom15071032 - 17 Jul 2025
Viewed by 177
Abstract
Temporal lobe epilepsy (TLE) is a common drug-resistant form of epilepsy, often accompanied by cognitive and emotional disturbances, highlighting the urgent need for novel therapies. Scorpion Venom Heat-Resistant Synthetic Peptide (SVHRSP), isolated and synthetically derived from scorpion venom, has shown anti-epileptic and neuroprotective [...] Read more.
Temporal lobe epilepsy (TLE) is a common drug-resistant form of epilepsy, often accompanied by cognitive and emotional disturbances, highlighting the urgent need for novel therapies. Scorpion Venom Heat-Resistant Synthetic Peptide (SVHRSP), isolated and synthetically derived from scorpion venom, has shown anti-epileptic and neuroprotective potential. This study evaluated the anti-epileptic effects of SVHRSP in a kainic acid (KA)-induced TLE rat model. Our results demonstrated that SVHRSP (0.81 mg/kg/day) reduced the frequency and severity of spontaneous seizures. Behavioral tests showed improved cognitive performance in the novel object recognition, object location, and T-maze tasks, as well as reduced anxiety-like behavior in the open-field test. Moreover, SVHRSP mitigated hippocampal neuronal loss and glial activation. Transcriptomic analysis indicated that SVHRSP upregulates genes involved in adhesion molecule-triggered and axon guidance pathways. Western blotting and immunofluorescence further confirmed that SVHRSP restored dendritic (MAP2), axonal (NFL), and synaptic (PSD95) marker expression, elevated the functionally important L1CAM fragment (L1-70), and increased myelin basic protein-induced serine protease activity responsible for L1-70 generation. Blockade of L1CAM expression diminished the neuroprotective effects of SVHRSP, suggesting a critical role for L1CAM-mediated synapse functions. This study is the first to reveal the therapeutic potential of SVHRSP in TLE via L1CAM-associated mechanisms. Full article
(This article belongs to the Section Molecular Medicine)
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23 pages, 1935 KiB  
Review
Heterologous Caseins: The Role of Phosphorylation in Their Functionality and How to Achieve It
by Soledad Mora Vásquez, Santiago García-Jacobo, Guy A. Cardineau and Silverio García-Lara
Biomolecules 2025, 15(7), 1031; https://doi.org/10.3390/biom15071031 - 17 Jul 2025
Viewed by 151
Abstract
Heterologous expression of caseins in non-mammalian systems offers a sustainable and scalable alternative for producing milk proteins, with potential applications in the food and biopharmaceutical industries. However, a significant challenge in these systems is achieving proper phosphorylation, a critical post-translational modification required for [...] Read more.
Heterologous expression of caseins in non-mammalian systems offers a sustainable and scalable alternative for producing milk proteins, with potential applications in the food and biopharmaceutical industries. However, a significant challenge in these systems is achieving proper phosphorylation, a critical post-translational modification required for casein functionality and stability. This review explores the current state of research on heterologous casein production, with a particular focus on the biological and technical hurdles associated with phosphorylation. Specifically, we examine the absence of the mammalian-specific kinase Fam20C in plant and yeast systems and the broader lack of secretory kinase machinery in bacteria, which collectively contribute to impaired phosphorylation fidelity. While some endogenous kinases may partially compensate, they are typically insufficient to replicate the phosphorylation pattern required for functionality. We evaluate potential strategies to address these limitations, analyze the role of phosphorylation in casein functionality, provide insights into existing patents and experimental approaches, and highlight ongoing research efforts. By synthesizing current knowledge and proposing new avenues for innovation, this review aims to provide a roadmap for the successful production of functional heterologous caseins. Full article
(This article belongs to the Section Molecular Biology)
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10 pages, 1970 KiB  
Correction
Correction: Lambert et al. Cytochalasans and Their Impact on Actin Filament Remodeling. Biomolecules 2023, 13, 1247
by Christopher Lambert, Katharina Schmidt, Marius Karger, Marc Stadler, Theresia E. B. Stradal and Klemens Rottner
Biomolecules 2025, 15(7), 1030; https://doi.org/10.3390/biom15071030 - 16 Jul 2025
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Abstract
In the original publication [...] Full article
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16 pages, 1415 KiB  
Article
Targeted Overexpression of Mitochondrial ALDH2 in Coronary Endothelial Cells Mitigates HFpEF in a Diabetic Mouse Model
by Guodong Pan, Bipradas Roy, Emmanuel Oppong Yeboah, Thomas Lanigan, Roland Hilgarth, Rajarajan A. Thandavarayan, Michael C. Petriello, Shailendra Giri and Suresh Selvaraj Palaniyandi
Biomolecules 2025, 15(7), 1029; https://doi.org/10.3390/biom15071029 - 16 Jul 2025
Viewed by 185
Abstract
Heart failure (HF) has become an epidemic, with a prevalence of ~7 million cases in the USA. Despite accounting for nearly 50% of all HF cases, heart failure with a preserved ejection fraction (HFpEF) remains challenging to treat. Common pathophysiological mechanisms in HFpEF [...] Read more.
Heart failure (HF) has become an epidemic, with a prevalence of ~7 million cases in the USA. Despite accounting for nearly 50% of all HF cases, heart failure with a preserved ejection fraction (HFpEF) remains challenging to treat. Common pathophysiological mechanisms in HFpEF include oxidative stress, microvascular dysfunction, and chronic unresolved inflammation. Our lab focuses on oxidative stress-mediated cellular dysfunction, particularly the toxic effects of lipid peroxidation products like 4-hydroxy-2-nonenal (4HNE). Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, plays a vital role in detoxifying 4HNE and thereby protecting the heart against pathological stress. ALDH2 activity is reduced in various metabolic stress-mediated cardiac pathologies. The dysfunction of coronary vascular endothelial cells (CVECs) is critical in initiating HFpEF development. Thus, we hypothesized that ectopic overexpression of ALDH2 in CVECs could mitigate metabolic stress-induced HFpEF pathogenesis. In this study, we tested the efficacy of intracardiac injections of the ALDH2 gene into CVECs in db/db mice—a model of obesity-induced type 2 diabetes mellitus (T2DM)—and their controls, db/m mice, by injection with ALDH2 constructs (AAV9-VE-cadherin-hALDH2-HA tag-P2A) or control constructs (AAV9-VE-cadherin-HA tag-P2A-eGFP). We found that intracardiac ALDH2 gene transfer increased ALDH2 levels specifically in CVECs compared to other myocardial cells. Additionally, we observed increased ALDH2 levels and activity, along with decreased 4HNE adducts, in the hearts of mice receiving ALDH2 gene transfer compared to control GFP transfer. Furthermore, ALDH2 gene transfer to CVECs improved diastolic function compared to GFP control alone. In conclusion, ectopic ALDH2 expression in CVECs can contribute, at least partially, to the amelioration of HFpEF. Full article
(This article belongs to the Special Issue Mitochondrial Proteins: From Import and Biogenesis to Complex Functional Network)
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21 pages, 3177 KiB  
Review
Galectin-3: Integrator of Signaling via Hexosamine Flux
by Mana Mohan Mukherjee, Devin Biesbrock and John Allan Hanover
Biomolecules 2025, 15(7), 1028; https://doi.org/10.3390/biom15071028 - 16 Jul 2025
Viewed by 75
Abstract
Galectin-3 (Gal-3) is a β-galactoside-binding lectin that mediates diverse signaling events in multiple cell types, including immune cells. It is also a prognostic indicator for multiple clinically important disorders, including cardiovascular disease. Gal-3 binds to cell surface glycans to form lattices that modulate [...] Read more.
Galectin-3 (Gal-3) is a β-galactoside-binding lectin that mediates diverse signaling events in multiple cell types, including immune cells. It is also a prognostic indicator for multiple clinically important disorders, including cardiovascular disease. Gal-3 binds to cell surface glycans to form lattices that modulate surface receptor signaling and internalization. However, the tissue-specific regulation of Gal-3 surface expression remains poorly understood. Here, we review evidence for the involvement of Gal-3 in cell surface signaling, intranuclear events, and intracellular trafficking. Our focus will be on the O-GlcNAc modification as a regulator of Gal-3 biosynthesis, non-canonical secretion, and recycling. We argue that the nutrient-driven cytoplasmic hexosamine biosynthetic pathway (HBP) and endomembrane transport mechanisms generate unique pools of nucleotide sugars. The differing levels of nucleotide sugars in the cytosol, endoplasmic reticulum (ER), and Golgi apparatus generate differential thresholds for the responsiveness of O-GlcNAc cycling, N- and O-linked glycan synthesis/branching, and glycolipid synthesis. By regulating Gal-3 synthesis and non-canonical secretion, O-GlcNAc cycling may serve as a nexus constraining Gal-3 cell surface expression and lattice formation. This homeostatic feedback mechanism would be critical under conditions where extensive glycan synthesis and branching in the endomembrane system and on the cell surface are maintained by elevated hexosamine synthesis. Thus, O-GlcNAc cycling and Gal-3 synergize to regulate Gal-3 secretion and influence cellular signaling. In humans, Gal-3 serves as an early-stage prognostic indicator for heart disease, kidney disease, viral infection, autoimmune disease, and neurodegenerative disorders. Since O-GlcNAc cycling has also been linked to these pathologic states, exploring the interconnections between O-GlcNAc cycling and Gal-3 expression and synthesis is likely to emerge as an exciting area of research. Full article
(This article belongs to the Special Issue Cell Biology and Biomedical Application of Galectins)
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53 pages, 2310 KiB  
Review
Metabolic Reprogramming in Respiratory Viral Infections: A Focus on SARS-CoV-2, Influenza, and Respiratory Syncytial Virus
by Jordi Camps, Simona Iftimie, Andrea Jiménez-Franco, Antoni Castro and Jorge Joven
Biomolecules 2025, 15(7), 1027; https://doi.org/10.3390/biom15071027 - 16 Jul 2025
Viewed by 121
Abstract
Respiratory infections caused by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus pose significant global health challenges, leading to high morbidity and mortality, particularly in vulnerable populations. Despite their distinct virological characteristics, these viruses exploit host cellular metabolism to [...] Read more.
Respiratory infections caused by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus pose significant global health challenges, leading to high morbidity and mortality, particularly in vulnerable populations. Despite their distinct virological characteristics, these viruses exploit host cellular metabolism to support replication, modulate immune responses, and promote disease progression. Emerging evidence shows that they induce metabolic reprogramming, shifting cellular energy production toward glycolysis to meet the bioenergetic demands of viral replication. Additionally, alterations in lipid metabolism, including enhanced fatty acid synthesis and disrupted cholesterol homeostasis, facilitate viral entry, replication, and immune evasion. The dysregulation of mitochondrial function and oxidative stress pathways also contributes to disease severity and long-term complications, such as persistent inflammation and immune exhaustion. Understanding these metabolic shifts is crucial for identifying new therapeutic targets and novel biomarkers for early disease detection, prognosis, and patient stratification. This review provides an overview of the metabolic alterations induced by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus, highlighting shared and virus-specific mechanisms and potential therapeutic interventions. Full article
(This article belongs to the Special Issue Metabolic Pathways, COVID-19 and Other Viral Acute Respiratory Infections: Mechanisms and Clinical Implications: 2nd Edition)
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30 pages, 1106 KiB  
Review
Transcription-Coupled Nucleotide Excision Repair: A Faster Solution or the Only Option?
by Andriy Khobta and Leen Sarmini
Biomolecules 2025, 15(7), 1026; https://doi.org/10.3390/biom15071026 - 16 Jul 2025
Viewed by 252
Abstract
A branch of the nucleotide excision repair (NER) pathway, transcription-coupled repair (TCR or TC-NER) specifically operates on the template DNA strand of actively transcribed genes. Initiated by stalling of elongating RNA polymerase complexes at damaged sites, TC-NER has historically been viewed as “accelerated [...] Read more.
A branch of the nucleotide excision repair (NER) pathway, transcription-coupled repair (TCR or TC-NER) specifically operates on the template DNA strand of actively transcribed genes. Initiated by stalling of elongating RNA polymerase complexes at damaged sites, TC-NER has historically been viewed as “accelerated repair”, arguably necessary for the maintenance of vital transcription function. Conversely, the conventional “global genome” (GG-NER) mechanism, operating throughout the genome, is usually regarded as a much slower process, even though it has long been found that differences in repair kinetics between transcribed DNA and the rest of the genome are not manifested for all structural types of DNA damage. Considering that damage detection is the rate-limiting step of overall repair reactions in most cases and that the mechanisms of the initial recognition of modified DNA structure are fundamentally different between TC-NER and GG-NER, it is suggestive to attribute the observed kinetic differences to different damage spectra recognized by the two pathways. This review summarizes current knowledge on the differential requirements of TC-NER and GG-NER towards specific damage types, based on their structural rather than spatial characteristics, and highlights some common features of DNA modifications repaired preferentially or exclusively by TC-NER, while evading other repair mechanisms. Full article
(This article belongs to the Special Issue Molecular Mechanisms in DNA and RNA Damage and Repair)
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18 pages, 9984 KiB  
Article
Integrated Multi-Omics of the Longissimus Dorsal Muscle Transcriptomics and Metabolomics Reveals Intramuscular Fat Accumulation Mechanism with Diet Energy Differences in Yaks
by Jingying Deng, Pengjia Bao, Ning Li, Siyuan Kong, Tong Wang, Minghao Zhang, Qinran Yu, Xinyu Cao, Jianlei Jia and Ping Yan
Biomolecules 2025, 15(7), 1025; https://doi.org/10.3390/biom15071025 - 16 Jul 2025
Viewed by 89
Abstract
IMF (intramuscular fat, IMF), as a key index for evaluating meat quality traits (shear force and cooking loss, etc.), and its deposition process are jointly regulated by nutritional and genetic factors. In this study, we analyzed the molecular regulation mechanism of IMF deposition [...] Read more.
IMF (intramuscular fat, IMF), as a key index for evaluating meat quality traits (shear force and cooking loss, etc.), and its deposition process are jointly regulated by nutritional and genetic factors. In this study, we analyzed the molecular regulation mechanism of IMF deposition in the LD (longissimus dorsal muscle, LD) by dietary energy level in Pamir yaks. Meat quality assessment showed that the meat quality of the High-energy diet group (1.53 MJ/Kg, G) and the Medium-energy diet group (1.38 MJ/Kg, Z) were significantly improved compared with that of the Low-energy diet group (0.75 MJ/Kg, C), in which IMF content in the LD of yaks in G group was significantly higher (p < 0.05) compared with Z and C groups. Further analysis by combined transcriptomics and lipid metabolomics revealed that the differences in IMF deposition mainly originated from the metabolism of lipids, such as TG (triglycerides, TG), PS (phosphatidylserine, PS), and LPC (lysophosphatidylcholine, LPC), and were influenced by SFRP4, FABP4, GADD45A, PDGFRA, RBP4, and DGAT2 genes, further confirming the importance of lipid–gene interactions in IMF deposition. This study reveals the energy-dependent epigenetic regulatory mechanism of IMF deposition in plateau ruminants, which provides molecular targets for optimizing yak nutritional strategies and quality meat production, while having important theoretical and practical value for the sustainable development of livestock husbandry on the Tibetan Plateau. Full article
(This article belongs to the Section Molecular Genetics)
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16 pages, 32599 KiB  
Article
The Connection Between Lipid Metabolism in the Heart and Liver of Wuzhishan Pigs
by Yuwei Ren, Feng Wang, Ruiping Sun, Xinli Zheng, Yanning Lin and Zhe Chao
Biomolecules 2025, 15(7), 1024; https://doi.org/10.3390/biom15071024 - 16 Jul 2025
Viewed by 116
Abstract
Lipid metabolism is critical for the physiological activities of signal transduction, metabolic regulation, and energy provision, and Wuzhishan (WZS) pigs are a promising animal model for studying human diseases. However, lipid metabolites in the heart and liver of WZS pigs are indistinct. In [...] Read more.
Lipid metabolism is critical for the physiological activities of signal transduction, metabolic regulation, and energy provision, and Wuzhishan (WZS) pigs are a promising animal model for studying human diseases. However, lipid metabolites in the heart and liver of WZS pigs are indistinct. In this study, we detected gene expression, blood biochemical parameters, and metabolic profiles of hearts and livers of WZS and Large White (LW) pigs, and analyzed correlations between metabolites. The results showed that the fatty acid metabolic process was present in both the heart and liver, and was more dominant in the liver. Although the expression of lipid absorption-related genes of CYP7A1 increased in the liver, CEBPB levels increased in both the liver and heart; the fatty acid beta-oxidation genes RXRA and ACSS2 also showed increased expression. The quantity of metabolites related to lipid synthesis decreased in the liver, heart, and blood for WZS pigs compared to that of LW pigs, indicating a balance of lipid synthesis and breakdown for WZS pigs. Moreover, the lipid metabolites in the liver and heart exhibited strong correlations with each other and showed similar correlations to blood biochemical parameters, respectively. This study declared the balance of lipid metabolism in both the heart and liver, and identified their connections for WZS pigs. Full article
(This article belongs to the Section Molecular Medicine)
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13 pages, 655 KiB  
Review
Three-Dimensional Models of Implantation Using Human Stem Cells: Scientific Insights and Broader Considerations
by Megan Munsie and Jock K. Findlay
Biomolecules 2025, 15(7), 1023; https://doi.org/10.3390/biom15071023 - 16 Jul 2025
Viewed by 156
Abstract
The ability to model the earliest stages of human embryonic development in vitro using pluripotent stem cells offers researchers new ways to understand and interrogate the intricacies of implantation. It also raises important ethical and regulatory considerations, both those common to research involving [...] Read more.
The ability to model the earliest stages of human embryonic development in vitro using pluripotent stem cells offers researchers new ways to understand and interrogate the intricacies of implantation. It also raises important ethical and regulatory considerations, both those common to research involving human embryos, as well as those unique to stem cell-based embryo and endometrial models. This review examines the underpinning scientific discoveries that have led to the development of this rapidly expanding area of research, and how three-dimensional embryo models could be employed in advancing assisted reproductive technologies and understanding implantation failure. Importantly, we also discuss the ethical and legal implications and explore various governance models that have been proposed to foster responsibility and innovation in this area of research. Given the heightened interest in the scientific community on this topic, we finish on the question of how and when to involve the public in the development of this technology and its regulation. Full article
(This article belongs to the Special Issue Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling)
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37 pages, 7439 KiB  
Review
A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways
by Sameena Mateen, Jordan Oman, Soha Haniyyah, Kavita Sharma, Ali Aghazadeh-Habashi and Srinath Pashikanti
Biomolecules 2025, 15(7), 1022; https://doi.org/10.3390/biom15071022 - 16 Jul 2025
Viewed by 257
Abstract
Sphingolipids (SLs) are a class of bioactive lipids characterized by sphingoid bases (SBs) as their backbone structure. These molecules exhibit distinct cellular functions, including cell growth, apoptosis, senescence, migration, and inflammatory responses, by interacting with esterases, amidases, kinases, phosphatases, and membrane receptors. These [...] Read more.
Sphingolipids (SLs) are a class of bioactive lipids characterized by sphingoid bases (SBs) as their backbone structure. These molecules exhibit distinct cellular functions, including cell growth, apoptosis, senescence, migration, and inflammatory responses, by interacting with esterases, amidases, kinases, phosphatases, and membrane receptors. These interactions result in a highly interconnected network of enzymes and pathways, known as the sphingolipidome. Dysregulation within this network is implicated in the onset and progression of cardiovascular diseases, metabolic disorders, neurodegenerative disorders, autoimmune diseases, and various cancers. This review highlights the pharmacologically significant sphingoid-based medicinal agents in preclinical and clinical studies. These include myriocin, fingolimod, fenretinide, safingol, spisulosine (ES-285), jaspine B, D-e-MAPP, B13, and α-galactosylceramide. It covers enantioselective syntheses, drug development efforts, and advances in molecular modeling to facilitate an understanding of the binding interactions of these compounds with their biological targets. This review provides a comprehensive evaluation of chiral pool synthetic strategies, translational studies, and the pharmacological relevance of sphingolipid-based drug candidates, offering a pathway for future research in sphingolipid-based therapeutic development. Full article
(This article belongs to the Topic Design, Synthesis and Biological Evaluation of Novel Small Molecules as Multi-target Enzyme Inhibitors)
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25 pages, 24158 KiB  
Communication
Generation of Novel Monoclonal Antibodies Recognizing Rabbit CD34 Antigen
by Jaromír Vašíček, Miroslav Bauer, Eva Kontseková, Andrej Baláži, Andrea Svoradová, Linda Dujíčková, Eva Tvrdá, Jakub Vozaf, Peter Supuka and Peter Chrenek
Biomolecules 2025, 15(7), 1021; https://doi.org/10.3390/biom15071021 - 15 Jul 2025
Viewed by 222
Abstract
The rabbit is a widely used experimental model for human translational research and stem cell therapy. Many studies have focused on rabbit mesenchymal stem cells from different biological sources for their possible application in regenerative medicine. However, a minimal number of studies have [...] Read more.
The rabbit is a widely used experimental model for human translational research and stem cell therapy. Many studies have focused on rabbit mesenchymal stem cells from different biological sources for their possible application in regenerative medicine. However, a minimal number of studies have been published aimed at rabbit hematopoietic stem/progenitor cells, mainly due to the lack of specific anti-rabbit CD34 antibodies. In general, CD34 antigen is commonly used to identify and isolate hematopoietic stem/progenitor cells in humans and other animal species. The aim of this study was to develop novel monoclonal antibodies highly specific to rabbit CD34 antigen. We used hybridoma technology, two synthetic peptides derived from predicted rabbit CD34 protein, and a recombinant rabbit CD34 protein as immunogens to produce monoclonal antibodies (mAbs) specific to rabbit CD34. The produced antibodies were screened for their binding activity and specificity using ELISA, flow cytometry, and Western blot analysis. Finally, four mAbs (58/47/26, 58/47/34, 182/7/80, and 575/36/8) were selected for the final purification process. The purified mAbs recognized up to 2–3% of total rabbit bone marrow cells, while about 2% of those cells exhibited CD45 expression, which are likely rabbit primitive hematopoietic stem cells and their hematopoietic progenitors, respectively. The newly generated and purified mAbs specifically recognize CD34 antigen in rabbit bone marrow or peripheral blood and can be therefore used for further immunological applications, to study rabbit hematopoiesis or to establish a new animal model for hematopoietic stem cell transplantation studies. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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23 pages, 1140 KiB  
Review
A Scoping Review of Sarcoglycan Expression in Non-Muscle Organs: Beyond Muscles
by Fabiana Nicita, Josè Freni, Antonio Centofanti, Angelo Favaloro, Davide Labellarte, Giuseppina Cutroneo, Michele Runci Anastasi and Giovanna Vermiglio
Biomolecules 2025, 15(7), 1020; https://doi.org/10.3390/biom15071020 - 15 Jul 2025
Viewed by 158
Abstract
This scoping review explores the expression patterns and molecular features of sarcoglycans (SGs) in non-muscle organs, challenging the long-standing assumption that their function is confined to skeletal and cardiac muscle. By analyzing evidence from both animal models and human studies, the review highlights [...] Read more.
This scoping review explores the expression patterns and molecular features of sarcoglycans (SGs) in non-muscle organs, challenging the long-standing assumption that their function is confined to skeletal and cardiac muscle. By analyzing evidence from both animal models and human studies, the review highlights the widespread presence of SG subunits in organs, including the nervous system, glands, adipose tissue, oral mucosa, retina, and other structures, with distinct regional and cell-type-specific patterns. Studies on the central nervous system demonstrate a widespread “spot-like” distribution of SG subunits in neurons and glial cells, implicating their involvement in synaptic organization and neurotransmission. Similarly, SGs maintain cellular integrity and homeostasis in glands and adipose tissue. At the same time, the altered expression of SGs is associated with pathological conditions in the gingival epithelium of the oral mucosa. These findings underscore the multifaceted roles of SGs beyond muscle, suggesting that they may contribute to cellular signaling, membrane stability, and neurovascular coupling. However, significant gaps remain regarding SG post-translational modifications and functional implications in non-muscle organs. Future research integrating molecular, cellular, and functional approaches in animal models and human tissues is essential to fully elucidate these roles and explore their potential as therapeutic targets in various diseases. Full article
(This article belongs to the Special Issue Biomolecules and Materials Based Approaches in Biomedical Field: 2nd Edition)
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