TY - JOUR AU - Abdisa, Kenbon Beyene AU - Szerdahelyi, Emőke AU - Molnár, Máté András AU - Friedrich, László AU - Lakner, Zoltán AU - Koris, András AU - Tóth, Attila AU - Nath, Arijit TI - Metabolic Syndrome and Biotherapeutic Activity of Dairy (Cow and Buffalo) Milk Proteins and Peptides: Fast Food-Induced Obesity Perspective—A Narrative Review JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 4 SP - 478 SN - 2218-273X DO - 10.3390/biom14040478 UR - https://m2.mtmt.hu/api/publication/34820678 ID - 34820678 AB - Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article. LA - English DB - MTMT ER - TY - JOUR AU - Sofio, Sara P. C. AU - Caeiro, André AU - Ribeiro, Ana C. F. AU - Cabral, Ana M. T. D. P. V. AU - Valente, Artur J. M. AU - Canhoto, Jorge AU - Esteso, Miguel A. TI - On Interactions of Sulfamerazine with Cyclodextrins from Coupled Diffusometry and Toxicity Tests JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 4 SP - 462 SN - 2218-273X DO - 10.3390/biom14040462 UR - https://m2.mtmt.hu/api/publication/34786009 ID - 34786009 AB - This scientific study employs the Taylor dispersion technique for diffusion measurements to investigate the interaction between sulfamerazine (NaSMR) and macromolecular cyclodextrins (β-CD and HP-β-CD). The results reveal that the presence of β-CD influences the diffusion of the solution component, NaSMR, indicating a counterflow of this drug due to solute interaction. However, diffusion data indicate no inclusion of NaSMR within the sterically hindered HP-β-CD cavity. Additionally, toxicity tests were conducted, including pollen germination (Actinidia deliciosa) and growth curve assays in BY-2 cells. The pollen germination tests demonstrate a reduction in sulfamerazine toxicity, suggesting potential applications for this antimicrobial agent with diminished adverse effects. This comprehensive investigation contributes to a deeper understanding of sulfamerazine–cyclodextrin interactions and their implications for pharmaceutical and biological systems. LA - English DB - MTMT ER - TY - JOUR AU - Jacksi, Mevan Fahmi Sami AU - Schad, Eva AU - Tantos, Agnes TI - Morphological Changes Induced by TKS4 Deficiency Can Be Reversed by EZH2 Inhibition in Colorectal Carcinoma Cells JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 4 SP - 445 SN - 2218-273X DO - 10.3390/biom14040445 UR - https://m2.mtmt.hu/api/publication/34773735 ID - 34773735 AB - Background: The scaffold protein tyrosine kinase substrate 4 (TKS4) undergoes tyrosine phosphorylation by the epidermal growth factor receptor (EGFR) pathway via Src kinase. The TKS4 deficiency in humans is responsible for the manifestation of a genetic disorder known as Frank–Ter Haar syndrome (FTHS). Based on our earlier investigation, the absence of TKS4 triggers migration, invasion, and epithelial–mesenchymal transition (EMT)-like phenomena while concurrently suppressing cell proliferation in HCT116 colorectal carcinoma cells. This indicates that TKS4 may play a unique role in the progression of cancer. In this study, we demonstrated that the enhancer of zeste homolog 2 (EZH2) and the histone methyltransferase of polycomb repressive complex 2 (PRC2) are involved in the migration, invasion, and EMT-like changes in TKS4-deficient cells (KO). EZH2 is responsible for the maintenance of the trimethylated lysine 27 on histone H3 (H3K27me3). Methods: We performed transcriptome sequencing, chromatin immunoprecipitation, protein and RNA quantitative studies, cell mobility, invasion, and proliferation studies combined with/without the EZH2 activity inhibitor 3-deazanoplanocine (DZNep). Results: We detected an elevation of global H3K27me3 levels in the TKS4 KO cells, which could be reduced with treatment with DZNep, an EZH2 inhibitor. Inhibition of EZH2 activity reversed the phenotypic effects of the knockout of TKS4, reducing the migration speed and wound healing capacity of the cells as well as decreasing the invasion capacity, while the decrease in cell proliferation became stronger. In addition, inhibition of EZH2 activity also reversed most epithelial and mesenchymal markers. We investigated the wider impact of TKS4 deletion on the gene expression profile of colorectal cancer cells using transcriptome sequencing of wild-type and TKS4 knockout cells, particularly before and after treatment with DZNep. Additionally, we observed changes in the expression of several protein-coding genes and long non-coding RNAs that showed a recovery in expression levels following EZH2 inhibition. Conclusions: Our results indicate that the removal of TKS4 causes a notable disruption in the gene expression pattern, leading to the disruption of several signal transduction pathways. Inhibiting the activity of EZH2 can restore most of these transcriptomics and phenotypic effects in colorectal carcinoma cells. LA - English DB - MTMT ER - TY - JOUR AU - Liu, M. AU - Srivastava, G. AU - Ramanujam, J. AU - Brylinski, M. TI - SynerGNet: A Graph Neural Network Model to Predict Anticancer Drug Synergy JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 3 SN - 2218-273X DO - 10.3390/biom14030253 UR - https://m2.mtmt.hu/api/publication/34818644 ID - 34818644 N1 - Division of Electrical and Computer Engineering, Louisiana State University, Baton Rouge, LA 70803, United States Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, United States Center for Computation and Technology, Louisiana State University, Baton Rouge, LA 70803, United States Export Date: 24 April 2024 Correspondence Address: Brylinski, M.; Department of Biological Sciences, United States; email: michal@brylinski.org Chemicals/CAS: Antineoplastic Agents Funding text 1: This work has been supported in part by the Center for Computation and Technology at Louisiana State University. AB - Drug combination therapy shows promise in cancer treatment by addressing drug resistance, reducing toxicity, and enhancing therapeutic efficacy. However, the intricate and dynamic nature of biological systems makes identifying potential synergistic drugs a costly and time-consuming endeavor. To facilitate the development of combination therapy, techniques employing artificial intelligence have emerged as a transformative solution, providing a sophisticated avenue for advancing existing therapeutic approaches. In this study, we developed SynerGNet, a graph neural network model designed to accurately predict the synergistic effect of drug pairs against cancer cell lines. SynerGNet utilizes cancer-specific featured graphs created by integrating heterogeneous biological features into the human protein–protein interaction network, followed by a reduction process to enhance topological diversity. Leveraging synergy data provided by AZ-DREAM Challenges, the model yields a balanced accuracy of 0.68, significantly outperforming traditional machine learning. Encouragingly, augmenting the training data with carefully constructed synthetic instances improved the balanced accuracy of SynerGNet to 0.73. Finally, the results of an independent validation conducted against DrugCombDB demonstrated that it exhibits a strong performance when applied to unseen data. SynerGNet shows a great potential in detecting drug synergy, positioning itself as a valuable tool that could contribute to the advancement of combination therapy for cancer treatment. © 2024 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Devrnja, N. AU - Anđelković, B. AU - Ljujić, J. AU - Ćosić, T. AU - Stupar, S. AU - Milutinović, M. AU - Savić, J. TI - Encapsulation of Fennel and Basil Essential Oils in β-Cyclodextrin for Novel Biopesticide Formulation JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 3 SN - 2218-273X DO - 10.3390/biom14030353 UR - https://m2.mtmt.hu/api/publication/34816439 ID - 34816439 N1 - Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11108, Serbia Faculty of Chemistry, University of Belgrade, Studentski trg 16, Belgrade, 11000, Serbia Export Date: 24 April 2024 Correspondence Address: Devrnja, N.; Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, Bulevar despota Stefana 142, Serbia; email: nina.devrnja@ibiss.bg.ac.rs LA - English DB - MTMT ER - TY - JOUR AU - Liu, H. AU - Li, X. AU - Shi, Y. AU - Ye, Z. AU - Cheng, X. TI - Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 3 SN - 2218-273X DO - 10.3390/biom14030342 UR - https://m2.mtmt.hu/api/publication/34798567 ID - 34798567 N1 - Zhejiang Cancer Hospital, Hangzhou, 310022, China Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, China The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058, China Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China Export Date: 18 April 2024 Correspondence Address: Ye, Z.; Zhejiang Cancer HospitalChina; email: yezuqscx@zju.edu.cn Correspondence Address: Cheng, X.; Zhejiang Cancer HospitalChina; email: chengxd@zjcc.org.cn Chemicals/CAS: cyclin dependent kinase 2, 141349-86-2; matrilysin, 141256-52-2; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; paclitaxel, 33069-62-4; pentamidine, 100-33-4; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, 210488-47-4; protein kinase B, 148640-14-6; protein tyrosine phosphatase, 79747-53-8, 97162-86-2; receptor type tyrosine protein phosphatase C; Smad protein, 62395-38-4; STAT5a protein, 176744-10-8; stress activated protein kinase, 155215-87-5 Funding details: 2022E10021 Funding details: Natural Science Foundation of Zhejiang Province, ZJNSF, LTGY23H160018 Funding details: 2024KY789 Funding text 1: This work was supported by the Key Laboratory of Prevention, Diagnosis, and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province (2022E10021). This research was also supported by the Natural Science Foundation of Zhejiang Province of China (Grant No. LTGY23H160018) and the Zhejiang Medical and Health Science and Technology Program (Grant No. 2024KY789) to Zu Ye. AB - Protein phosphatases are primarily responsible for dephosphorylation modification within signal transduction pathways. Phosphatase of regenerating liver-3 (PRL-3) is a dual-specific phosphatase implicated in cancer pathogenesis. Understanding PRL-3’s intricate functions and developing targeted therapies is crucial for advancing cancer treatment. This review highlights its regulatory mechanisms, expression patterns, and multifaceted roles in cancer progression. PRL-3’s involvement in proliferation, migration, invasion, metastasis, angiogenesis, and drug resistance is discussed. Regulatory mechanisms encompass transcriptional control, alternative splicing, and post-translational modifications. PRL-3 exhibits selective expressions in specific cancer types, making it a potential target for therapy. Despite advances in small molecule inhibitors, further research is needed for clinical application. PRL-3-zumab, a humanized antibody, shows promise in preclinical studies and clinical trials. Our review summarizes the current understanding of the cancer-related cellular function of PRL-3, its prognostic value, and the research progress of therapeutic inhibitors. © 2024 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Hu, W. AU - Parkinson, C. AU - Zheng, H. TI - Mechanistic Insights Revealed by YbtPQ in the Occluded State JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 3 SN - 2218-273X DO - 10.3390/biom14030322 UR - https://m2.mtmt.hu/api/publication/34794582 ID - 34794582 N1 - Export Date: 17 April 2024 Correspondence Address: Zheng, H.; Department of Biochemistry and Molecular Genetics, Mail Stop 8101, University of Colorado Anschutz Medical Campus, United States; email: hongjin.zheng@cuanschutz.edu Chemicals/CAS: adenosine diphosphate, 20398-34-9, 58-64-0; adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; benzylsulfonyl fluoride, 329-98-6; orthovanadic acid, 14333-18-7; vanadic acid, 12260-63-8, 13981-20-9, 37353-31-4; Adenosine Triphosphate; ATP-Binding Cassette Transporters; Vanadates Tradenames: Ni NTA resin; superose 6 column, GE Healthcare; Titan Krios, Thermo Manufacturers: GE Healthcare; Thermo Funding details: Office of Science, SC Funding details: Oregon Health and Science University, OHSU Funding details: National Institutes of Health, NIH, R21 AI175646, U24GM129547 Funding details: National Institutes of Health, NIH Funding details: Biological and Environmental Research, BER, U24 GM129541 Funding details: Biological and Environmental Research, BER Funding text 1: A portion of this research was supported by NIH grant U24GM129547 and performed at the Pacific Northwest Center for Cryo-EM (PNCC) at Oregon Health & Sciences University (OHSU) and accessed through EMSL (grid.436923.9), a DOE Office of Science User Facility sponsored by the Office of Biological and Environmental Research. Some work was also performed at the Stanford-SLAC Cryo-EM Center (S2C2) (supported by the NIH U24 GM129541). Specifically, we thank Theo Humphreys from PNCC for the final Cryo-EM data collection. Funding text 2: This work is partially supported by NIH (R21 AI175646). AB - Recently, several ATP-binding cassette (ABC) importers have been found to adopt the typical fold of type IV ABC exporters. Presumably, these importers would function under the transport scheme of “alternating access” like those exporters, cycling through inward-open, occluded, and outward-open conformations. Understanding how the exporter-like importers move substrates in the opposite direction requires structural studies on all the major conformations. To shed light on this, here we report the structure of yersiniabactin importer YbtPQ from uropathogenic Escherichia coli in the occluded conformation trapped by ADP-vanadate (ADP-Vi) at a 3.1 Å resolution determined by cryo-electron microscopy. The structure shows unusual local rearrangements in multiple helices and loops in its transmembrane domains (TMDs). In addition, the dimerization of the nucleotide-binding domains (NBDs) promoted by the vanadate trapping is highlighted by the “screwdriver” action at one of the two hinge points. These structural observations are rare and thus provide valuable information to understand the structural plasticity of the exporter-like ABC importers. © 2024 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Viljetic, Barbara AU - Blazetic, Senka AU - Labak, Irena AU - Ivic, Vedrana AU - Zjalic, Milorad AU - Heffer, Marija AU - Balog, Marta TI - Lipid Rafts: The Maestros of Normal Brain Development JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 3 PG - 25 SN - 2218-273X DO - 10.3390/biom14030362 UR - https://m2.mtmt.hu/api/publication/34789509 ID - 34789509 N1 - Funding Agency and Grant Number: Croatian Science Foundation Funding text: Figure 1 was created with https://www.biorender.com/ (accessed on 18 January 2024). AB - Lipid rafts, specialised microdomains within cell membranes, play a central role in orchestrating various aspects of neurodevelopment, ranging from neural differentiation to the formation of functional neuronal networks. This review focuses on the multifaceted involvement of lipid rafts in key neurodevelopmental processes, including neural differentiation, synaptogenesis and myelination. Through the spatial organisation of signalling components, lipid rafts facilitate precise signalling events that determine neural fate during embryonic development and in adulthood. The evolutionary conservation of lipid rafts underscores their fundamental importance for the structural and functional complexity of the nervous system in all species. Furthermore, there is increasing evidence that environmental factors can modulate the composition and function of lipid rafts and influence neurodevelopmental processes. Understanding the intricate interplay between lipid rafts and neurodevelopment not only sheds light on the fundamental mechanisms governing brain development but also has implications for therapeutic strategies aimed at cultivating neuronal networks and addressing neurodevelopmental disorders. LA - English DB - MTMT ER - TY - JOUR AU - Salaudeen, M.A. AU - Bello, N. AU - Danraka, R.N. AU - Ammani, M.L. TI - Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 3 SN - 2218-273X DO - 10.3390/biom14030305 UR - https://m2.mtmt.hu/api/publication/34786861 ID - 34786861 N1 - Division of Neuroscience, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, M13 9PL, United Kingdom Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, 810107, Nigeria Department of Pharmacology and Therapeutics, Faculty of Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, 840001, Nigeria Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Kaduna State University, Kaduna, 800283, Nigeria Export Date: 12 April 2024 Correspondence Address: Salaudeen, M.A.; Division of Neuroscience, United Kingdom; email: maryam.salaudeen@manchester.ac.uk Chemicals/CAS: Neuroprotective Agents Funding details: University of Manchester, UoM Funding text 1: M.A.S. is sponsored by the University of Manchester President Doctoral Scholarship Award. AB - The majority of approved therapies for many diseases are developed to target their underlying pathophysiology. Understanding disease pathophysiology has thus proven vital to the successful development of clinically useful medications. Stroke is generally accepted as the leading cause of adult disability globally and ischemic stroke accounts for the most common form of the two main stroke types. Despite its health and socioeconomic burden, there is still minimal availability of effective pharmacological therapies for its treatment. In this review, we take an in-depth look at the etiology and pathophysiology of ischemic stroke, including molecular and cellular changes. This is followed by a highlight of drugs, cellular therapies, and complementary medicines that are approved or undergoing clinical trials for the treatment and management of ischemic stroke. We also identify unexplored potential targets in stroke pathogenesis that can be exploited to increase the pool of effective anti-stroke and neuroprotective agents through de novo drug development and drug repurposing. © 2024 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Wang, K. AU - Hu, G. AU - Wu, Z. AU - Uversky, V.N. AU - Kurgan, L. TI - Assessment of Disordered Linker Predictions in the CAID2 Experiment JF - BIOMOLECULES J2 - BIOMOLECULES VL - 14 PY - 2024 IS - 3 SN - 2218-273X DO - 10.3390/biom14030287 UR - https://m2.mtmt.hu/api/publication/34785005 ID - 34785005 N1 - School of Statistics and Data Science, LPMC and KLMDASR, Nankai University, Tianjin, 300071, China School of Mathematical Sciences and LPMC, Nankai University, Tianjin, 300071, China Department of Molecular Medicine, USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, United States Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, United States Export Date: 11 April 2024 Correspondence Address: Kurgan, L.; Department of Computer Science, United States; email: lkurgan@vcu.edu Chemicals/CAS: protein, 67254-75-5; Intrinsically Disordered Proteins; Proteins Funding details: National Science Foundation, NSF, DBI2146027, IIS2125218 Funding details: National Science Foundation, NSF Funding details: National Natural Science Foundation of China, NSFC, 92370128, 12326611 Funding details: National Natural Science Foundation of China, NSFC Funding text 1: This research was supported in part by the National Science Foundation [grant numbers DBI2146027 and IIS2125218 to L.K.], the National Natural Science Foundation of China [grant number 92370128 to G.H. and Z.W. and 12326611 to K.W and G.H.], and the Robert J. Mattauch Endowment funds to L.K. AB - Disordered linkers (DLs) are intrinsically disordered regions that facilitate movement between adjacent functional regions/domains, contributing to many key cellular functions. The recently completed second Critical Assessments of protein Intrinsic Disorder prediction (CAID2) experiment evaluated DL predictions by considering a rather narrow scenario when predicting 40 proteins that are already known to have DLs. We expand this evaluation by using a much larger set of nearly 350 test proteins from CAID2 and by investigating three distinct scenarios: (1) prediction residues in DLs vs. in non-DL regions (typical use of DL predictors); (2) prediction of residues in DLs vs. other disordered residues (to evaluate whether predictors can differentiate residues in DLs from other types of intrinsically disordered residues); and (3) prediction of proteins harboring DLs. We find that several methods provide relatively accurate predictions of DLs in the first scenario. However, only one method, APOD, accurately identifies DLs among other types of disordered residues (scenario 2) and predicts proteins harboring DLs (scenario 3). We also find that APOD’s predictive performance is modest, motivating further research into the development of new and more accurate DL predictors. We note that these efforts will benefit from a growing amount of training data and the availability of sophisticated deep network models and emphasize that future methods should provide accurate results across the three scenarios. © 2024 by the authors. LA - English DB - MTMT ER -