Biomolecules

16 pages, 3381 KiB

Open AccessArticle

Structural and Thermodynamic Insights into Dimerization In-Terfaces of Drosophila Glutathione Transferases

by Mathieu Schwartz, Nicolas Petiot, Jeanne Chaloyard, Véronique Senty-Segault, Frédéric Lirussi, Patrick Senet, Adrien Nicolai, Jean-Marie Heydel, Francis Canon, Sanjiv Sonkaria, Varsha Khare, Claude Didierjean and Fabrice Neiers

Biomolecules 2024, 14(7), 758; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070758 (registering DOI) - 26 Jun 2024

Abstract

This study presents a comprehensive analysis of the dimerization interfaces of fly GSTs through sequence alignment. Our investigation revealed GSTE1 as a particularly intriguing target, providing valuable insights into the variations within Delta and Epsilon GST interfaces. The X-ray structure of GSTE1 was [...] Read more.

This study presents a comprehensive analysis of the dimerization interfaces of fly GSTs through sequence alignment. Our investigation revealed GSTE1 as a particularly intriguing target, providing valuable insights into the variations within Delta and Epsilon GST interfaces. The X-ray structure of GSTE1 was determined, unveiling remarkable thermal stability and a distinctive dimerization interface. Utilizing circular dichroism, we assessed the thermal stability of GSTE1 and other Drosophila GSTs with resolved X-ray structures. The subsequent examination of GST dimer stability correlated with the dimerization interface supported by findings from X-ray structural analysis and thermal stability measurements. Our discussion extends to the broader context of GST dimer interfaces, offering a generalized perspective on their stability. This research enhances our understanding of the structural and thermodynamic aspects of GST dimerization, contributing valuable insights to the field. Full article

(This article belongs to the Special Issue The Multiple Roles of Glutathione-Dependent Enzymes: A Themed Issue in Honor of Prof. Bengt Mannervik)

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15 pages, 1441 KiB

Open AccessArticle

Extracellular Vesicle-Mediated Modulation of Stem-like Phenotype in Breast Cancer Cells under Fluid Shear Stress

by Spenser R. Brown, Margaret E. Radcliffe, Joseph T. Danner, Wilmer J. Andújar Cruz, Kimberly H. Lackey, Han-A Park, Steven T. Weinman and Yonghyun Kim

Biomolecules 2024, 14(7), 757; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070757 (registering DOI) - 25 Jun 2024

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Abstract

Circulating tumor cells (CTCs) are some of the key culprits that cause cancer metastasis and metastasis-related deaths. These cells exist in a dynamic microenvironment where they experience fluid shear stress (FSS), and the CTCs that survive FSS are considered to be highly metastatic [...] Read more.

Circulating tumor cells (CTCs) are some of the key culprits that cause cancer metastasis and metastasis-related deaths. These cells exist in a dynamic microenvironment where they experience fluid shear stress (FSS), and the CTCs that survive FSS are considered to be highly metastatic and stem cell-like. Biophysical stresses such as FSS are also known to cause the production of extracellular vesicles (EVs) that can facilitate cell–cell communication by carrying biomolecular cargos such as microRNAs. Here, we hypothesized that physiological FSS will impact the yield of EV production, and that these EVs will have biomolecules that transform the recipient cells. The EVs were isolated using direct flow filtration with and without FSS from the MDA-MB-231 cancer cell line, and the expression of key stemness-related genes and microRNAs was characterized. There was a significantly increased yield of EVs under FSS. These EVs also contained significantly increased levels of miR-21, which was previously implicated to promote metastatic progression and chemotherapeutic resistance. When these EVs from FSS were introduced to MCF-7 cancer cells, the recipient cells had a significant increase in their stem-like gene expression and CD44⁺/CD24⁻ cancer stem cell-like subpopulation. There was also a correlated increased proliferation along with an increased ATP production. Together, these findings indicate that the presence of physiological FSS can directly influence the EVs’ production and their contents, and that the EV-mediated transfer of miR-21 can have an important role in FSS-existing contexts, such as in cancer metastasis. Full article

(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery: Unveiling the Next Frontier)

16 pages, 1339 KiB

Open AccessArticle

Evaluation of the Effect of β-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression

by Lennart Höfs, David Geißler-Lösch, Kristof M. Wunderlich, Eva M. Szegö, Chris Van den Haute, Veerle Baekelandt, Wolfgang Hoyer and Björn H. Falkenburger

Biomolecules 2024, 14(7), 756; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070756 (registering DOI) - 25 Jun 2024

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Abstract

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric [...] Read more.

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFFs). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence staining were used as outcomes. Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or the degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression. Full article

(This article belongs to the Special Issue Synuclein Proteins II)

12 pages, 20671 KiB

Open AccessArticle

In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease

by Yuri Alves de Oliveira Só, Katyanna Sales Bezzera, Ricardo Gargano, Fabio L. L. Mendonça, Janeusa Trindade Souto, Umberto L. Fulco, Marcelo Lopes Pereira Junior and Luiz Antônio Ribeiro Junior

Biomolecules 2024, 14(7), 755; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070755 (registering DOI) - 25 Jun 2024

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Abstract

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, which is a potent inhibitor that targets the SARS-CoV-2 M^pro, shows promise as an antiviral treatment. Additionally, Ivermectin, which is a broad-spectrum antiparasitic drug, has demonstrated effectiveness [...] Read more.

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, which is a potent inhibitor that targets the SARS-CoV-2 M^pro, shows promise as an antiviral treatment. Additionally, Ivermectin, which is a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods, such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interacted with SARS-CoV-2 M^pro(A). Calculations using density functional theory were instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids, like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding, with a root-mean-square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized M^pro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19. Full article

(This article belongs to the Section Chemical Biology)

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16 pages, 1118 KiB

Open AccessReview

FLASH Radiotherapy: Mechanisms of Biological Effects and the Therapeutic Potential in Cancer

by Ouying Yan, Shang Wang, Qiaoli Wang and Xin Wang

Biomolecules 2024, 14(7), 754; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070754 (registering DOI) - 25 Jun 2024

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Abstract

Radiotherapy is an important treatment for many unresectable advanced malignant tumors, and radiotherapy-associated inflammatory reactions to radiation and other toxic side effects are significant reasons which reduce the quality of life and survival of patients. FLASH-radiotherapy (FLASH-RT), a prominent topic in recent radiation [...] Read more.

Radiotherapy is an important treatment for many unresectable advanced malignant tumors, and radiotherapy-associated inflammatory reactions to radiation and other toxic side effects are significant reasons which reduce the quality of life and survival of patients. FLASH-radiotherapy (FLASH-RT), a prominent topic in recent radiation therapy research, is an ultra-high dose rate treatment known for significantly reducing therapy time while effectively targeting tumors. This approach minimizes radiation side effects on at-risk organs and maximally protects surrounding healthy tissues. Despite decades of preclinical exploration and some notable achievements, the mechanisms behind FLASH effects remain debated. Standardization is still required for the type of FLASH-RT rays and dose patterns. This review addresses the current state of FLASH-RT research, summarizing the biological mechanisms behind the FLASH effect. Additionally, it examines the impact of FLASH-RT on immune cells, cytokines, and the tumor immune microenvironment. Lastly, this review will discuss beam characteristics, potential clinical applications, and the relevance and applicability of FLASH-RT in treating advanced cancers. Full article

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17 pages, 4069 KiB

Open AccessReview

The Role of Hyperuricemia in Cardiac Diseases: Evidence, Controversies, and Therapeutic Strategies

by Yue Zheng, Zhirui Chen, Jinya Yang, Jing Zheng, Xiaorong Shui, Yiguang Yan, Shian Huang, Zheng Liang, Wei Lei and Yuan He

Biomolecules 2024, 14(7), 753; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070753 (registering DOI) - 25 Jun 2024

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Abstract

dial infarction, arrhythmias, and heart failure. We also combined recent findings from basic research to analyze potential mechanisms linking HUA with myocardial injury. In different pathological models (such as direct action of high uric acid on myocardial cells or combined with myocardial ischemia-reperfusion [...] Read more.

dial infarction, arrhythmias, and heart failure. We also combined recent findings from basic research to analyze potential mechanisms linking HUA with myocardial injury. In different pathological models (such as direct action of high uric acid on myocardial cells or combined with myocardial ischemia-reperfusion model), HUA may cause damage by activating the NOD-like receptor protein 3 inflammasome-induced inflammatory response, interfering with cardiac cell energy metabolism, affecting antioxidant defense systems, and stimulating reactive oxygen species production to enhance the oxidative stress response, ultimately resulting in decreased cardiac function. Additionally, we discuss the impact of lowering uric acid intervention therapy and potential safety issues that may arise. However, as the mechanism underlying HUA-induced myocardial injury is poorly defined, further research is warranted to aid in the development novel therapeutic strategies for HUA-related cardiovascular diseases. Full article

(This article belongs to the Special Issue New Insights into Cardiometabolic Diseases)

21 pages, 2236 KiB

Open AccessArticle

Enhanced ε-Poly-L-Lysine Production in Streptomyces albulus through Multi-Omics-Guided Metabolic Engineering

by Liang Wang, Hao Yang, Mengping Wu, Hongjian Zhang, Jianhua Zhang and Xusheng Chen

Biomolecules 2024, 14(7), 752; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070752 (registering DOI) - 25 Jun 2024

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Abstract

Safe and eco-friendly preservatives are crucial to preventing food spoilage and illnesses, as foodborne diseases caused by pathogens result in approximately 600 million cases of illness and 420,000 deaths annually. ε-Poly-L-lysine (ε-PL) is a novel food preservative widely used in many countries. However, [...] Read more.

Safe and eco-friendly preservatives are crucial to preventing food spoilage and illnesses, as foodborne diseases caused by pathogens result in approximately 600 million cases of illness and 420,000 deaths annually. ε-Poly-L-lysine (ε-PL) is a novel food preservative widely used in many countries. However, its commercial application has been hindered by high costs and low production. In this study, ε-PL’s biosynthetic capacity was enhanced in Streptomyces albulus WG608 through metabolic engineering guided by multi-omics techniques. Based on transcriptome and metabolome data, differentially expressed genes (fold change >2 or <0.5; p < 0.05) and differentially expressed metabolites (fold change >1.2 or <0.8) were separately subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The integrative analysis of transcriptome, metabolome, and overexpression revealed the essential roles of isocitrate lyase, succinate dehydrogenase, flavoprotein subunit, diaminopimelate dehydrogenase, polyphosphate kinase, and polyP:AMP phosphotransferase in ε-PL biosynthesis. Subsequently, a strain with enhanced ATP supply, L-lysine supply, and ε-PL synthetase expression was constructed to improve its production. Finally, the resulting strain, S. albulus WME10, achieved an ε-PL production rate of 77.16 g/L in a 5 L bioreactor, which is the highest reported ɛ-PL production to date. These results suggest that the integrative analysis of the transcriptome and metabolome can facilitate the identification of key pathways and genetic elements affecting ε-PL synthesis, guiding further metabolic engineering and thus significantly enhancing ε-PL production. The method presented in this study could be applicable to other valuable natural antibacterial agents. Full article

3 pages, 1532 KiB

Open AccessCorrection

Correction: Firoozi et al. A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction. Biomolecules 2020, 10, 205

by Saman Firoozi, Sara Pahlavan, Mohammad-Hossein Ghanian, Shahram Rabbani, Shima Tavakol, Maryam Barekat, Saeed Yakhkeshi, Elena Mahmoudi, Mansoureh Soleymani and Hossein Baharvand

Biomolecules 2024, 14(7), 751; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070751 (registering DOI) - 25 Jun 2024

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Abstract

The authors wish to make the following corrections to this paper [...] Full article

(This article belongs to the Special Issue Self-Assembling Peptides)

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24 pages, 4494 KiB

Open AccessArticle

Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases

by Mariano Nigro, Israél Sánchez-Moreno, Raúl Benito-Arenas, Ana L. Valino, Adolfo M. Iribarren, Nicolás Veiga, Eduardo García-Junceda and Elizabeth S. Lewkowicz

Biomolecules 2024, 14(7), 750; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070750 (registering DOI) - 25 Jun 2024

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Abstract

Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, [...] Read more.

Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, the chirality of the aliphatic chain, which mimics the open pentose residue, is crucial for activity. In this work, three DHAP-dependent aldolases: fructose-1,6-biphosphate aldolase from rabbit muscle, rhanmulose-1-phosphate aldolase from Thermotoga maritima, and fuculose-1-phosphate aldolase from Escherichia coli, were used as biocatalysts. Aldehyde derivatives of thymine and cytosine were used as acceptor substrates, generating new acyclic nucleoside analogues containing two new stereocenters with conversion yields between 70% and 90%. Moreover, structural analyses by molecular docking were carried out to gain insights into the diasteromeric excess observed. Full article

(This article belongs to the Special Issue Biotechnological and Biomedical Applications of Enzymes Involved in the Synthesis of Nucleosides and Nucleotides—2nd Edition)

15 pages, 2999 KiB

Open AccessArticle

TFTF: An R-Based Integrative Tool for Decoding Human Transcription Factor–Target Interactions

by Jin Wang

Biomolecules 2024, 14(7), 749; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070749 - 24 Jun 2024

Viewed by 288

Abstract

Transcription factors (TFs) are crucial in modulating gene expression and sculpting cellular and organismal phenotypes. The identification of TF–target gene interactions is pivotal for comprehending molecular pathways and disease etiologies but has been hindered by the demanding nature of traditional experimental approaches. This [...] Read more.

Transcription factors (TFs) are crucial in modulating gene expression and sculpting cellular and organismal phenotypes. The identification of TF–target gene interactions is pivotal for comprehending molecular pathways and disease etiologies but has been hindered by the demanding nature of traditional experimental approaches. This paper introduces a novel web application and package utilizing the R program, which predicts TF–target gene relationships and vice versa. Our application integrates the predictive power of various bioinformatic tools, leveraging their combined strengths to provide robust predictions. It merges databases for enhanced precision, incorporates gene expression correlation for accuracy, and employs pan-tissue correlation analysis for context-specific insights. The application also enables the integration of user data with established resources to analyze TF–target gene networks. Despite its current limitation to human data, it provides a platform to explore gene regulatory mechanisms comprehensively. This integrated, systematic approach offers researchers an invaluable tool for dissecting the complexities of gene regulation, with the potential for future expansions to include a broader range of species. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

13 pages, 3477 KiB

Open AccessReview

Molecular Mechanisms and Potential Antiviral Strategies of Liquid–Liquid Phase Separation during Coronavirus Infection

by Ying Wang, Liying Zhou, Xiaohan Wu, Shixing Yang, Xiaochun Wang, Quan Shen, Yuwei Liu, Wen Zhang and Likai Ji

Biomolecules 2024, 14(7), 748; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070748 - 24 Jun 2024

Viewed by 303

Abstract

Highly pathogenic coronaviruses have caused significant outbreaks in humans and animals, posing a serious threat to public health. The rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in millions of infections and deaths. However, the mechanisms through which coronaviruses [...] Read more.

Highly pathogenic coronaviruses have caused significant outbreaks in humans and animals, posing a serious threat to public health. The rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in millions of infections and deaths. However, the mechanisms through which coronaviruses evade a host’s antiviral immune system are not well understood. Liquid–liquid phase separation (LLPS) is a recently discovered mechanism that can selectively isolate cellular components to regulate biological processes, including host antiviral innate immune signal transduction pathways. This review focuses on the mechanism of coronavirus-induced LLPS and strategies for utilizing LLPS to evade the host antiviral innate immune response, along with potential antiviral therapeutic drugs and methods. It aims to provide a more comprehensive understanding and novel insights for researchers studying LLPS induced by pandemic viruses. Full article

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22 pages, 24995 KiB

Open AccessArticle

Expression Proteomics and Histone Analysis Reveal Extensive Chromatin Network Changes and a Role for Histone Tail Trimming during Cellular Differentiation

by Giorgio Oliviero, Kieran Wynne, Darrell Andrews, John Crean, Walter Kolch and Gerard Cagney

Biomolecules 2024, 14(7), 747; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070747 - 24 Jun 2024

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Abstract

In order to understand the coordinated proteome changes associated with differentiation of a cultured cell pluripotency model, protein expression changes induced by treatment of NT2 embryonal carcinoma cells with retinoic acid were monitored by mass spectrometry. The relative levels of over 5000 proteins [...] Read more.

In order to understand the coordinated proteome changes associated with differentiation of a cultured cell pluripotency model, protein expression changes induced by treatment of NT2 embryonal carcinoma cells with retinoic acid were monitored by mass spectrometry. The relative levels of over 5000 proteins were mapped across distinct cell fractions. Analysis of the chromatin fraction revealed major abundance changes among chromatin proteins and epigenetic pathways between the pluripotent and differentiated states. Protein complexes associated with epigenetic regulation of gene expression, chromatin remodelling (e.g., SWI/SNF, NuRD) and histone-modifying enzymes (e.g., Polycomb, MLL) were found to be extensively regulated. We therefore investigated histone modifications before and after differentiation, observing changes in the global levels of lysine acetylation and methylation across the four canonical histone protein families, as well as among variant histones. We identified the set of proteins with affinity to peptides housing the histone marks H3K4me3 and H3K27me3, and found increased levels of chromatin-associated histone H3 tail trimming following differentiation that correlated with increased expression levels of cathepsin proteases. We further found that inhibition of cathepsins B and D reduces histone H3 clipping. Overall, the work reveals a global reorganization of the cell proteome congruent with differentiation, highlighting the key role of multiple epigenetic pathways, and demonstrating a direct link between cathepsin B and D activity and histone modification. Full article

(This article belongs to the Section Molecular Biology)

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33 pages, 1802 KiB

Open AccessReview

Bridging the Gap in Cancer Research: Sulfur Metabolism of Leukemic Cells with a Focus on L-Cysteine Metabolism and Hydrogen Sulfide-Producing Enzymes

by Konrad Kaleta, Klaudia Janik, Leszek Rydz, Maria Wróbel and Halina Jurkowska

Biomolecules 2024, 14(7), 746; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070746 - 24 Jun 2024

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Abstract

Leukemias are cancers of the blood-forming system, representing a significant challenge in medical science. The development of leukemia cells involves substantial disturbances within the cellular machinery, offering hope in the search for effective selective treatments that could improve the 5-year survival rate. Consequently, [...] Read more.

Leukemias are cancers of the blood-forming system, representing a significant challenge in medical science. The development of leukemia cells involves substantial disturbances within the cellular machinery, offering hope in the search for effective selective treatments that could improve the 5-year survival rate. Consequently, the pathophysiological processes within leukemia cells are the focus of critical research. Enzymes such as cystathionine beta-synthase and sulfurtransferases like thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine gamma-lyase play a vital role in cellular sulfur metabolism. These enzymes are essential to maintaining cellular homeostasis, providing robust antioxidant defenses, and supporting cell division. Numerous studies have demonstrated that cancerous processes can alter the expression and activity of these enzymes, uncovering potential vulnerabilities or molecular targets for cancer therapy. Recent laboratory research has indicated that certain leukemia cell lines may exhibit significant changes in the expression patterns of these enzymes. Analysis of the scientific literature and online datasets has confirmed variations in sulfur enzyme function in specific leukemic cell lines compared to normal leukocytes. This comprehensive review collects and analyzes available information on sulfur enzymes in normal and leukemic cell lines, providing valuable insights and identifying new research pathways in this field. Full article

(This article belongs to the Section Molecular Medicine)

15 pages, 2312 KiB

Open AccessArticle

Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase

by Ilya V. Fateev, Sobirdjan A. Sasmakov, Jaloliddin M. Abdurakhmanov, Abdukhakim A. Ziyaev, Shukhrat Sh. Khasanov, Farkhod B. Eshboev, Oybek N. Ashirov, Valeriya D. Frolova, Barbara Z. Eletskaya, Olga S. Smirnova, Maria Ya. Berzina, Alexandra O. Arnautova, Yulia A. Abramchik, Maria A. Kostromina, Alexey L. Kayushin, Konstantin V. Antonov, Alexander S. Paramonov, Valeria L. Andronova, Georgiy A. Galegov, Roman S. Esipov, Shakhnoz S. Azimova, Anatoly I. Miroshnikov and Irina D. Konstantinova Show full author list Hide full author list

Biomolecules 2024, 14(7), 745; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070745 - 24 Jun 2024

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Abstract

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this [...] Read more.

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this study was to synthesize ribosides and deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex viruses. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. Of six prepared nucleosides, the riboside and deoxyriboside of 3-phenacylthio-1,2,4-triazole were obtained at good yields. The yields of the disubstituted 1,2,4-triazol-3-thiones were low due to the effect of bulky substituents at the C3 and C5 positions on the selectivity of enzymatic glycosylation for one particular nitrogen atom in the triazole ring. The results of cytotoxic and antiviral studies on acyclovir-sensitive wild-type strain HSV-1/L2(TK+) and acyclovir-resistant strain (HSV-1/L2/R^ACV) in Vero E6 cell culture showed that the incorporation of a thiobutyl substituent into the C5 position of 3-phenyl-1,2,4-triazole results in a significant increase in the cytotoxicity of the base and antiviral activity. The highest antiviral activity was observed in the 3-phenacylthio-1-(β-D-ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-β-D-ribofuranosyl)-3-phenyl-1,2,4-triazole nucleosides, with their selectivity indexes being significantly higher than that of ribavirin. It was also found that with the increasing lipophilicity of the nucleosides, the activity and toxicity of the tested compounds increased. Full article

(This article belongs to the Special Issue Biotechnological and Biomedical Applications of Enzymes Involved in the Synthesis of Nucleosides and Nucleotides—2nd Edition)

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13 pages, 1549 KiB

Open AccessArticle

Correlation between Melatonin and Colostral Regulatory T Cells in Giardia lamblia Infection

by Adriele Ataides de Queiroz, Eduardo Luzía França, Gabriella Regina Borges Gadenz, Letícia Damas Leão Dalcin, Mahmi Fujimori, Danielle Cristina Honorio França, Maria Aparecida Gomes and Adenilda Cristina Honorio-França

Biomolecules 2024, 14(7), 744; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070744 - 24 Jun 2024

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Abstract

Giardiasis is a parasitic disease caused by Giardia lamblia (G. lamblia) that affects people worldwide. Still, few studies report on the immunoregulatory effects of the biomolecules of colostrum during interactions with G. lamblia. This study aimed to assess the concentrations [...] Read more.

Giardiasis is a parasitic disease caused by Giardia lamblia (G. lamblia) that affects people worldwide. Still, few studies report on the immunoregulatory effects of the biomolecules of colostrum during interactions with G. lamblia. This study aimed to assess the concentrations of melatonin and cortisol hormones, the percentage of Treg cells, and the levels of cytokines IL-10 and TGF-β in colostrum from mothers who tested positive for the parasite. This cross-sectional study analyzed colostrum samples from 25 puerperal. The samples were tested using an ELISA to determine if they were seropositive for G. lamblia and the type of antibody present (IgM and IgG). Based on the results, the samples were divided into three groups: a control group (N = 10) with no reaction to either IgM or IgG, a group seropositive for IgG (IgG⁺/IgM⁻; N = 8), and a group seropositive for IgM (IgM⁺/IgG⁻; N = 7). The concentrations of melatonin and cortisol were measured using the ELISA method. Additionally, cytokines IL-10 and TGF-β and immunophenotyping were analyzed using flow cytometry. In the group that tested positive for IgM anti-G. lamblia, the concentration of melatonin was lower. However, in the colostrum from mothers who tested positive for IgG anti-G. lamblia, the level of this hormone had increased. The cortisol levels were similar between the groups, regardless of seropositivity. There was a higher percentage of Treg cells in the colostrum from mothers who tested positive for IgM anti-G. lamblia. TGF-β levels also increased in the colostrum of mothers who tested positive for IgM anti-G. lamblia. In the seronegative group for G. lamblia, there was a positive correlation between melatonin concentration and the percentage of Treg cells. These data suggest that the increase in regulatory cells and cytokines and the reduction in melatonin in colostrum from mothers with recent giardia infection may contribute to the evolution and manifestation of the disease. Full article

(This article belongs to the Special Issue Melatonin in Normal Physiology and Disease)

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21 pages, 1537 KiB

Open AccessReview

AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment

by Shen Qu, Weili Jia, Ye Nie, Wen Shi, Chao Chen, Zihao Zhao and Wenjie Song

Biomolecules 2024, 14(7), 743; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070743 - 23 Jun 2024

Viewed by 373

Abstract

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and [...] Read more.

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and pancreatic cancers through invasion and metastasis. Notably, AGR2 not only serves as a pro-oncogenic agent but also as a downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into the established functions and expression patterns of AGR2, emphasizing its pivotal role in cancer progression, particularly in hepatobiliary and pancreatic malignancies. Furthermore, AGR2 emerges as a potential cancer prognostic marker and a promising target for immunotherapy, offering novel avenues for the treatment of hepatobiliary and pancreatic cancers and enhancing patient outcomes. Full article

(This article belongs to the Section Molecular Medicine)

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13 pages, 10308 KiB

Open AccessArticle

Bifidobacterium bifidum SAM-VI Riboswitch Conformation Change Requires Peripheral Helix Formation

by Wenwen Xiao, Guangfeng Liu, Ting Chen, Yunlong Zhang and Changrui Lu

Biomolecules 2024, 14(7), 742; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070742 - 23 Jun 2024

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Abstract

The Bifidobacterium bifidum SAM-VI riboswitch undergoes dynamic conformational changes that modulate downstream gene expression. Traditional structural methods such as crystallography capture the bound conformation at high resolution, and additional efforts would reveal details from the dynamic transition. Here, we revealed a transcription-dependent conformation [...] Read more.

The Bifidobacterium bifidum SAM-VI riboswitch undergoes dynamic conformational changes that modulate downstream gene expression. Traditional structural methods such as crystallography capture the bound conformation at high resolution, and additional efforts would reveal details from the dynamic transition. Here, we revealed a transcription-dependent conformation model for Bifidobacterium bifidum SAM-VI riboswitch. In this study, we combine small-angle X-ray scattering, chemical probing, and isothermal titration calorimetry to unveil the ligand-binding properties and conformational changes of the Bifidobacterium bifidum SAM-VI riboswitch and its variants. Our results suggest that the SAM-VI riboswitch contains a pre-organized ligand-binding pocket and stabilizes into the bound conformation upon binding to SAM. Whether the P1 stem formed and variations in length critically influence the conformational dynamics of the SAM-VI riboswitch. Our study provides the basis for artificially engineering the riboswitch by manipulating its peripheral sequences without modifying the SAM-binding core. Full article

(This article belongs to the Collection Feature Papers in Biomacromolecules: Nucleic Acids)

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27 pages, 17279 KiB

Open AccessArticle

Lumbrokinase Extracted from Earthworms Synergizes with Bevacizumab and Chemotherapeutics in Treating Non-Small Cell Lung Cancer by Targeted Inactivation of BPTF/VEGF and NF-κB/COX-2 Signaling

by Chunyu Hua, Ziyue Guo, Meng Dai, Jie Zhou, Hanxiao Ge, Guoqing Xue, Fahui Xu, Liyuan Ru, Kuan Lv, Guohui Zhang, Lina Zheng, Meiyi Wang, Yun Teng, Wendan Yu and Wei Guo

Biomolecules 2024, 14(7), 741; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070741 - 23 Jun 2024

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Abstract

As a kind of proteolytic enzyme extracted from earthworms, lumbrokinase has been used as an antithrombotic drug clinically. Nevertheless, its potential in anti-cancer, especially in anti-non-small cell lung cancer (NSCLC), as a single form of treatment or in combination with other therapies, [...] Read more.

As a kind of proteolytic enzyme extracted from earthworms, lumbrokinase has been used as an antithrombotic drug clinically. Nevertheless, its potential in anti-cancer, especially in anti-non-small cell lung cancer (NSCLC), as a single form of treatment or in combination with other therapies, is still poorly understood. In this study, we explored the anti-tumor role and the responsive molecular mechanisms of lumbrokinase in suppressing tumor angiogenesis and chemoresistance development in NSCLC and its clinical potential in combination with bevacizumab and chemotherapeutics. Lumbrokinase was found to inhibit cell proliferation in a concentration-dependent manner and caused metastasis suppression and apoptosis induction to varying degrees in NSCLC cells. Lumbrokinase enhanced the anti-angiogenesis efficiency of bevacizumab by down-regulating BPTF expression, decreasing its anchoring at the VEGF promoter region and subsequent VEGF expression and secretion. Furthermore, lumbrokinase treatment reduced IC50 values of chemotherapeutics and improved their cytotoxicity in parental and chemo-resistant NSCLC cells via inactivating the NF-κB pathway, inhibiting the expression of COX-2 and subsequent secretion of PGE2. LPS-induced NF-κB activation reversed its inhibition on NSCLC cell proliferation and its synergy with chemotherapeutic cytotoxicity, while COX-2 inhibitor celecoxib treatment boosted such effects. Lumbrokinase combined with bevacizumab, paclitaxel, or vincristine inhibited the xenograft growth of NSCLC cells in mice more significantly than a single treatment. In conclusion, lumbrokinase inhibited NSCLC survival and sensitized NSCLC cells to bevacizumab or chemotherapeutics treatment by targeted down-regulation of BPTF/VEGF signaling and inactivation of NF-κB/COX-2 signaling, respectively. The combinational applications of lumbrokinase with bevacizumab or chemotherapeutics are expected to be developed as promising candidate therapeutic strategies to improve the efficacy of the original monotherapy in anti-NSCLC. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

32 pages, 2053 KiB

Open AccessReview

Therapeutic Potential of Hydrogen Sulfide in Ischemia and Reperfusion Injury

by Xutao Sun, Siyu Wu, Caiyun Mao, Ying Qu, Zihang Xu, Ying Xie, Deyou Jiang and Yunjia Song

Biomolecules 2024, 14(7), 740; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070740 - 22 Jun 2024

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Abstract

Abstract: Ischemia–reperfusion (I/R) injury, a prevalent pathological condition in medical practice, presents significant treatment challenges. Hydrogen sulfide (H₂S), acknowledged as the third gas signaling molecule, profoundly impacts various physiological and pathophysiological processes. Extensive research has demonstrated that H₂S [...] Read more.

Abstract: Ischemia–reperfusion (I/R) injury, a prevalent pathological condition in medical practice, presents significant treatment challenges. Hydrogen sulfide (H₂S), acknowledged as the third gas signaling molecule, profoundly impacts various physiological and pathophysiological processes. Extensive research has demonstrated that H₂S can mitigate I/R damage across multiple organs and tissues. This review investigates the protective effects of H₂S in preventing I/R damage in the heart, brain, liver, kidney, intestines, lungs, stomach, spinal cord, testes, eyes, and other tissues. H₂S provides protection against I/R damage by alleviating inflammation and endoplasmic reticulum stress; inhibiting apoptosis, oxidative stress, and mitochondrial autophagy and dysfunction; and regulating microRNAs. Significant advancements in understanding the mechanisms by which H₂S reduces I/R damage have led to the development and synthesis of H₂S-releasing agents such as diallyl trisulfide-loaded mesoporous silica nanoparticles (DATS-MSN), AP39, zofenopril, and ATB-344, offering a new therapeutic avenue for I/R injury. Full article

19 pages, 950 KiB

Open AccessReview

Exploring the Link between Varicella-Zoster Virus, Autoimmune Diseases, and the Role of Recombinant Zoster Vaccine

by Ryuhei Ishihara, Ryu Watanabe, Mayu Shiomi, Masao Katsushima, Kazuo Fukumoto, Shinsuke Yamada, Tadashi Okano and Motomu Hashimoto

Biomolecules 2024, 14(7), 739; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070739 - 22 Jun 2024

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Abstract

The varicella-zoster virus (VZV) is a human neurotropic herpes virus responsible for varicella and herpes zoster (HZ). Following primary infection in childhood, VZV manifests as varicella (chickenpox) and enters a period of latency within the dorsal root ganglion. A compromised cellular immune response [...] Read more.

The varicella-zoster virus (VZV) is a human neurotropic herpes virus responsible for varicella and herpes zoster (HZ). Following primary infection in childhood, VZV manifests as varicella (chickenpox) and enters a period of latency within the dorsal root ganglion. A compromised cellular immune response due to aging or immunosuppression triggers viral reactivation and the development of HZ (shingles). Patients with autoimmune diseases have a higher risk of developing HZ owing to the immunodeficiency associated with the disease itself and/or the use of immunosuppressive agents. The introduction of new immunosuppressive agents with unique mechanisms has expanded the treatment options for autoimmune diseases but has also increased the risk of HZ. Specifically, Janus kinase (JAK) inhibitors and anifrolumab have raised concerns regarding HZ. Despite treatment advances, a substantial number of patients suffer from complications such as postherpetic neuralgia for prolonged periods. The adjuvanted recombinant zoster vaccine (RZV) is considered safe and effective even in immunocompromised patients. The widespread adoption of RZV may reduce the health and socioeconomic burdens of HZ patients. This review covers the link between VZV and autoimmune diseases, assesses the risk of HZ associated with immunosuppressant use, and discusses the benefits and risks of using RZV in patients with autoimmune diseases. Full article

20 pages, 507 KiB

Open AccessReview

The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway

by Haoming Tang, Xin Pang, Shun Li and Liling Tang

Biomolecules 2024, 14(7), 738; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070738 - 21 Jun 2024

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Abstract

(1) Background: The neddylation pathway assumes a pivotal role in the initiation and progression of cancer. MLN4924, a potent small-molecule inhibitor of the NEDD8-activating enzyme (NAE), effectively intervenes in the early stages of the neddylation pathway. By instigating diverse cellular responses, such as [...] Read more.

(1) Background: The neddylation pathway assumes a pivotal role in the initiation and progression of cancer. MLN4924, a potent small-molecule inhibitor of the NEDD8-activating enzyme (NAE), effectively intervenes in the early stages of the neddylation pathway. By instigating diverse cellular responses, such as senescence and apoptosis in cancer cells, MLN4924 also exerts regulatory effects on non-malignant cells within the tumor microenvironment (TME) and tumor virus-infected cells, thereby impeding the onset of tumors. Consequently, MLN4924 has been widely acknowledged as a potent anti-cancer drug. (2) Recent findings: Nevertheless, recent findings have illuminated additional facets of the neddylation pathway, revealing its active involvement in various biological processes detrimental to the survival of cancer cells. This newfound understanding underscores the dual role of MLN4924 in tumor therapy, characterized by both anti-cancer and pro-cancer effects. This dichotomy is herein referred to as the “double-edged effects” of MLN4924. This paper delves into the intricate relationship between the neddylation pathway and cancer, offering a mechanistic exploration and analysis of the causes underlying the double-edged effects of MLN4924—specifically, the accumulation of pro-cancer neddylation substrates. (3) Perspectives: Here, the objective is to furnish theoretical support and novel insights that can guide the development of next-generation anti-cancer drugs targeting the neddylation pathway. Full article

12 pages, 1151 KiB

Open AccessArticle

Macrophage Phenotype Induced by Circulating Small Extracellular Vesicles from Women with Endometriosis

by María Angeles Martínez-Zamora, Olga Armengol-Badia, Lara Quintas-Marquès, Francisco Carmona and Daniel Closa

Biomolecules 2024, 14(7), 737; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070737 - 21 Jun 2024

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Abstract

Evidence suggests that immune system dysfunction and macrophages are involved in the disease establishment and progression of endometriosis. Among the factors involved in this alteration in macrophage activity, Small Extracellular Vesicles (sEVs) have been described to play a role favoring the switch to [...] Read more.

Evidence suggests that immune system dysfunction and macrophages are involved in the disease establishment and progression of endometriosis. Among the factors involved in this alteration in macrophage activity, Small Extracellular Vesicles (sEVs) have been described to play a role favoring the switch to a specific phenotype with controversial results. This study aims to investigate the potential effect of circulating sEVs in the plasma of well-characterized patients with endometriosis on the polarization of macrophages. sEVs were isolated from the plasma of patients diagnosed with endometriosis confirmed by histopathological analysis. Two groups of patients were recruited: the endometriosis group consisted of patients diagnosed with endometriosis by imaging testing (gynecological ultrasonography and/or magnetic resonance imaging), confirmed by histopathologic study (n = 12), and the control group included patients who underwent laparoscopy for tubal sterilization without presurgical suspicion of endometriosis and without endometriosis or signs of any inflammatory pelvic condition during surgery (n = 12). Human THP1 monocytic cells were differentiated into macrophages, and the effect of sEVs on cell uptake and macrophage polarization was evaluated by fluorescent labeling and measurement of the IL1B, TNF, ARG1, and MRC1 expression, respectively. Although no changes in cell uptake were detected, sEVs from endometriosis induced a polarization of macrophages toward an M2 phenotype, characterized by lower IL1B and TNF expression and a tendency to increase MRC1 and ARG1 levels. When macrophages were stimulated with lipopolysaccharides, less activation was also detected after treatment with endometriosis sEVs. Finally, endometriosis sEVs also induced the expression of the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARG); however, treatment with rosiglitazone, a PPARG agonist, had no effect on the change in macrophage phenotype. We conclude that circulating sEVs in women with endometriosis have a certain capacity to shift the activation state of macrophages toward an M2 phenotype, but this does not modify the uptake level or the response to PPARG ligands. Full article

(This article belongs to the Topic The Role of Extracellular Vesicles as Modulators of the Tumor Microenvironment)

18 pages, 2586 KiB

Open AccessArticle

An Early Gestation Plasma Inflammasome in Rural Bangladeshi Women

by Hyunju Kim, Jacquelyn R. Bedsaul-Fryer, Kerry J. Schulze, Gwen Sincerbeaux, Sarah Baker, Casey M. Rebholz, Lee SF Wu, Joseph Gogain, Lena Cuddeback, James D. Yager, Luigi M. De Luca, Towfida J. Siddiqua and Keith P. West, Jr.

Biomolecules 2024, 14(7), 736; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070736 - 21 Jun 2024

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Abstract

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 [...] Read more.

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated the relative quantification of plasma proteins assessed via a multiplexed aptamer assay (SOMAScan^®) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate <0.05. We examined potential pathways using principal component analysis. A total of 147 and 879 of 6431 detected plasma proteins correlated with AGP and CRP, respectively, of which 61 overlapped with both biomarkers. Positive correlates included serum amyloid, complement, interferon-induced, and immunoregulatory proteins. Negative correlates were micronutrient and lipid transporters and pregnancy-related anabolic proteins. The principal components (PCs) of AGP were dominated by negatively correlated anabolic proteins associated with gestational homeostasis, angiogenesis, and neurogenesis. The PCs of CRP were more diverse in function, reflecting cell surface and adhesion, embryogenic, and intracellular and extra-hepatic tissue leakage proteins. The plasma proteome of AGP or CRP reveals wide proteomic variation associated with early gestational inflammation, suggesting mechanisms and pathways that merit future research. Full article

(This article belongs to the Special Issue Human Reproductive Biology: Uncertainties and Controversies)

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17 pages, 2727 KiB

Open AccessArticle

Concept of Normativity in Multi-Omics Analysis of Axon Regeneration

by Isabella Moceri, Sean Meehan, Emily Gonzalez, Kevin K. Park, Abigail Hackam, Richard K. Lee and Sanjoy Bhattacharya

Biomolecules 2024, 14(7), 735; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070735 - 21 Jun 2024

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Abstract

Transcriptomes and proteomes can be normalized with a handful of RNAs or proteins (or their peptides), such as GAPDH, β-actin, RPBMS, and/or GAP43. Even with hundreds of standards, normalization cannot be achieved across different molecular mass ranges for small molecules, such as lipids [...] Read more.

Transcriptomes and proteomes can be normalized with a handful of RNAs or proteins (or their peptides), such as GAPDH, β-actin, RPBMS, and/or GAP43. Even with hundreds of standards, normalization cannot be achieved across different molecular mass ranges for small molecules, such as lipids and metabolites, due to the non-linearity of mass by charge ratio for even the smallest part of the spectrum. We define the amount (or range of amounts) of metabolites and/or lipids per a defined amount of a protein, consistently identified in all samples of a multiple-model organism comparison, as the normative level of that metabolite or lipid. The defined protein amount (or range) is a normalized value for one cohort of complete samples for which intrasample relative protein quantification is available. For example, the amount of citrate (a metabolite) per µg of aconitate hydratase (normalized protein amount) identified in the proteome is the normative level of citrate with aconitase. We define normativity as the amount of metabolites (or amount range) detected when compared to normalized protein levels. We use axon regeneration as an example to illustrate the need for advanced approaches to the normalization of proteins. Comparison across different pharmacologically induced axon regeneration mouse models entails the comparison of axon regeneration, studied at different time points in several models designed using different agents. For the normalization of the proteins across different pharmacologically induced models, we perform peptide doping (fixed amounts of known peptides) in each sample to normalize the proteome across the samples. We develop Regen V peptides, divided into Regen III (SEB, LLO, CFP) and II (HH4B, A1315), for pre- and post-extraction comparisons, performed with the addition of defined, digested peptides (bovine serum albumin tryptic digest) for protein abundance normalization beyond commercial labeled relative quantification (for example, 18-plex tandem mass tags). We also illustrate the concept of normativity by using this normalization technique on regenerative metabolome/lipidome profiles. As normalized protein amounts are different in different biological states (control versus axon regeneration), normative metabolite or lipid amounts are expected to be different for specific biological states. These concepts and standardization approaches are important for the integration of different datasets across different models of axon regeneration. Full article

(This article belongs to the Special Issue Advances in Neuroproteomics)

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25 pages, 1930 KiB

Open AccessReview

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects

by Jesús I. Gil-Chinchilla, Agustín G. Zapata, Jose M. Moraleda and David García-Bernal

Biomolecules 2024, 14(7), 734; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14070734 - 21 Jun 2024

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Abstract

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit [...] Read more.

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects, diverse strategies have bioengineered MSCs to enhance their tumour targeting and therapeutic properties or to deliver anti-cancer drugs. In this review, we highlight the advanced uses of MSCs in cancer therapy, particularly as carriers of targeted treatments due to their natural tumour-homing capabilities. We also discuss the potential of MSC-derived extracellular vesicles to improve the efficiency of drug or molecule delivery to cancer cells. Ongoing clinical trials are evaluating the therapeutic potential of these cells and setting the stage for future advances in MSC-based cancer treatment. It is critical to identify the broad and potent applications of bioengineered MSCs in solid tumour targeting and anti-cancer agent delivery to position them as effective therapeutics in the evolving field of cancer therapy. Full article

(This article belongs to the Special Issue Applications of Mesenchymal Stem/Stromal Cells in Immuno-Oncology Therapy and The Priming Ways to Boost Their Functions)

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Biomolecules, Volume 14, Issue 7 (July 2024) – 25 articles

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