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10 pages, 1121 KiB  
Article
In Experimental Tuberculosis Infection, the Bacteriostatic Function of Macrophages Is Activated by Th1 CD4+ T-Effectors in a Nitrite-Independent Manner
by Vladimir V. Evstifeev, Konstantin B. Majorov, Vadim G. Avdienko, Vladimir V. Yeremeev and Galina S. Shepelkova
Int. J. Mol. Sci. 2025, 26(14), 6573; https://doi.org/10.3390/ijms26146573 - 8 Jul 2025
Viewed by 369
Abstract
The pivotal component in the protection against TB is the tissue macrophages (Mф). These cells have been demonstrated to play a crucial role in the elimination of pathogens and mycobacterial killing. Elucidation of the molecular and phenotypic events that determine the outcome of [...] Read more.
The pivotal component in the protection against TB is the tissue macrophages (Mф). These cells have been demonstrated to play a crucial role in the elimination of pathogens and mycobacterial killing. Elucidation of the molecular and phenotypic events that determine the outcome of infection in Mф is fundamental to understanding the key features of these cells that are so important in fighting infection. Mф activation is driven by cytokines and other inflammatory mediators secreted by T lymphocytes. The interaction between Mycobacterium tuberculosis (Mtb) and host Мф has been the subject of extensive in vitro research. This dynamic interplay represents a pivotal step in the progression of mycobacterial infection because pulmonary macrophages constitute the primary line of defense against the pathogen, thereby serving as the initial immune cells to which Mtb must adapt to establish a replicative foothold within the host. Our studies have demonstrated that highly differentiated Th1 effectors with the CD27low phenotype exhibit superior efficacy in activating both peritoneal (Mф: T cell ratio ranging from 125:1 to 625:1) and pulmonary macrophages (Mф: T cell ratio = 5:1) compared to cells with the CD27high phenotype. Furthermore, our findings indicate that this activation mechanism is not contingent upon the production of reactive nitrogen species. To effectively activate the bacteriostatic function of macrophages, CD27high T lymphocytes must differentiate into effectors with the CD27low phenotype. Full article
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33 pages, 4665 KiB  
Review
A Paradigm Shift in SSTI Management: The Multifunctional Role of Extracellular Vesicles
by Barathan Muttiah and Alfizah Hanafiah
Int. J. Mol. Sci. 2025, 26(13), 6481; https://doi.org/10.3390/ijms26136481 - 5 Jul 2025
Viewed by 683
Abstract
Skin and soft tissue infections (SSTIs) are becoming an urgent public health issue worldwide. The globe is facing a growing problem with drug-resistant germs, and current treatments are not quite cutting it. There is a real need for new therapies that can tackle [...] Read more.
Skin and soft tissue infections (SSTIs) are becoming an urgent public health issue worldwide. The globe is facing a growing problem with drug-resistant germs, and current treatments are not quite cutting it. There is a real need for new therapies that can tackle these challenges more effectively. This brings us to an interesting question: Can extracellular vesicles (EVs) from different sources, such as mesenchymal stem cells (MSCs), immune cells, or even plants and animals, help in treating SSTIs, especially given the rise in drug resistance? Studies have shown that MSC-derived EVs are particularly noteworthy because they carry components such as antimicrobial peptides (AMPs) that can work together to fight infections, boost the immune response, and aid in healing. These vesicles play a role in how our body interacts with infections, helping to clear bacteria, reduce inflammation, and promote tissue repair. We also see that EVs from plants and bacteria can directly fight off germs, while those from animals can support the healing process of skin. Although early studies have shown promise for EV therapies, there are still hurdles to overcome, such as ensuring consistent production and delivery. This review looks at the potential of EVs as powerful agents in managing infections and supporting healing, highlighting an exciting area of research in medicine. Full article
(This article belongs to the Special Issue Extracellular Vesicles: Advances in Multi-Omics)
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18 pages, 2398 KiB  
Review
The Therapeutic Potential of Antimicrobial Peptides Isolated from the Skin Secretions of Anurans of the Genus Boana in the Face of the Global Antimicrobial Resistance Crisis
by Priscila Mendes Ferreira, Fabiano Fagundes Moser da Silva, Joyce Silva dos Santos, Brunna de Oliveira Silva, Carlos José Correia de Santana, Osmindo Rodrigues Pires Júnior, Wagner Fontes and Mariana S. Castro
Toxins 2025, 17(7), 312; https://doi.org/10.3390/toxins17070312 - 20 Jun 2025
Viewed by 1067
Abstract
Microorganisms play a dual role in human health, serving as both essential allies and serious threats. Their association with infections led to the development of antimicrobials like penicillin, which revolutionized medicine. However, the emergence of antimicrobial resistance (AMR) has created a global health [...] Read more.
Microorganisms play a dual role in human health, serving as both essential allies and serious threats. Their association with infections led to the development of antimicrobials like penicillin, which revolutionized medicine. However, the emergence of antimicrobial resistance (AMR) has created a global health crisis, rendering many treatments ineffective due to pathogen mutations and acquired resistance mechanisms, particularly among ESKAPE pathogens. This resistance increases morbidity, mortality, and healthcare costs, exacerbated by antibiotic overuse and globalization. Biofilms and sepsis further complicate treatment. Addressing AMR requires new therapies, rational antibiotic use, and innovative approaches for drug discovery. Coordinated global action is essential to ensure future access to effective treatments. Antimicrobial peptides (AMPs) derived from Boana species (Anura, Hylidae) represent a promising alternative in the fight against AMR. These peptides exhibit activity against multidrug-resistant pathogens. Unlike conventional antibiotics, Boana peptides act through a broad mechanism that limits resistance development. Their ability to disrupt bacterial membranes and modulate immune responses makes them ideal candidates for the development of new treatments. These peptides may offer valuable alternatives for treating resistant infections and addressing the global AMR crisis. Full article
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28 pages, 1265 KiB  
Review
Polyphenols in Foods and Their Use in the Food Industry: Enhancing the Quality and Nutritional Value of Functional Foods
by Nurten Coşkun, Sümeyye Sarıtaş, Mikhael Bechelany and Sercan Karav
Int. J. Mol. Sci. 2025, 26(12), 5803; https://doi.org/10.3390/ijms26125803 - 17 Jun 2025
Viewed by 894
Abstract
Polyphenols are known as secondary metabolites, which are crucial bioactive compounds that play a significant role in enhancing human health. Chromatographic methods are typically used to identify polyphenols after food extraction. The extraction methods are fundamental, however, they are implemented with some differences, [...] Read more.
Polyphenols are known as secondary metabolites, which are crucial bioactive compounds that play a significant role in enhancing human health. Chromatographic methods are typically used to identify polyphenols after food extraction. The extraction methods are fundamental, however, they are implemented with some differences, including extractant type, according to the food. Polyphenols are mostly found in some foods, including grapes, olives, cherries, and apples. Foods have diverse polyphenols, which differ according to the food type. Moreover, they have flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins as various subgroups of polyphenols, which can change in terms of quantity and quality along with several factors, including the type, growing region, germination time, and harvest season of the food. The consumption of polyphenols is crucial for human health due to their anti-cancer, anti-tumor, anti-inflammatory, cardiometabolic risk management, antimicrobial, immunomodulatory, and antioxidant effects. In the valorization of polyphenols, the consumption dose is also important to effectively benefit from the polyphenols of plant-based foods. Several in vitro and in vivo studies have tested the polyphenols’ digestion ability and preservation ability in gut microbiota and their effect on the microbiota to determine the benefits and effects of polyphenols in several areas. According to these studies, polyphenols can be used to fight against disease. In addition, diverse applications, including encapsulation and polyphenol coating, are used to stabilize, preserve, and improve the bioaccessibility of polyphenols. Even though polyphenol-rich foods are consumed for nutrition in daily life, they are also used as nutritional ingredients in the food industry to produce functional foods, and functional foods are enriched with food by-products to enhance their nutritional value, especially in terms of polyphenols. Particularly, food by-products are used to enrich functional foods, which are preferred in healthy life diets due to the diversity and amount of bioactive ingredients, including the polyphenol types of the food by-products. Furthermore, polyphenols also provide the preservation ability of storage and improve the bioaccessibility of bioactive ingredients during the digestion of functional foods. This review article examines the polyphenol ingredients of several types of food used in the food industry. It explains the effective factors that affect the amount and type of food and determines the impact of polyphenols on polyphenol-enriched products and functional foods. The article also provides a brief exemplification of the value of polyphenol-rich food by-products in the context of functional food production. Several studies presented in this review article demonstrate the value of polyphenols, particularly in the food industry and functional food production. Full article
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40 pages, 2183 KiB  
Review
The Telomere Length Signature in Leukemias—From Molecular Mechanisms Underlying Telomere Shortening to Immunotherapeutic Options Against Telomerase
by Stella Baliou, Iordanis Pelagiadis, Miruna-Maria Apetroaei, Elena Vakonaki, Andreea Letiția Arsene, Eleftheria Hatzidaki, Manolis N. Tzatzarakis, Petros Ioannou, Aristides Tsatsakis and Eftichia Stiakaki
Cancers 2025, 17(12), 1936; https://doi.org/10.3390/cancers17121936 - 10 Jun 2025
Viewed by 950
Abstract
The nucleoprotein structures known as telomeres provide genomic integrity by protecting the ends of chromosomes. Tumorigenesis is associated with alterations in telomere function and stability. This narrative review provides evidence of the potential prognostic value of telomere length and telomerase in leukemias. On [...] Read more.
The nucleoprotein structures known as telomeres provide genomic integrity by protecting the ends of chromosomes. Tumorigenesis is associated with alterations in telomere function and stability. This narrative review provides evidence of the potential prognostic value of telomere length and telomerase in leukemias. On the one hand, oxidative stress and mitochondrial dysfunction can accelerate telomere shortening, leading to higher susceptibility and the progression of leukemia. On the other hand, cytogenetic alterations (such as gene fusions and chromosomal abnormalities) and genomic complexity can result from checkpoint dysregulation, the induction of the DNA damage response (DDR), and defective repair signaling at telomeres. This review thoroughly outlines the ways by which telomere dysfunction can play a key role in the development and progression of four primary leukemias, including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and acute leukemias of myeloid or lymphoid origin, highlighting the potential prognostic value of telomere length in this field. However, telomerase, which is highly active in leukemias, can prevent the rate of telomere attrition. In line with this, leukemia cells can proliferate, suggesting telomerase as a promising therapeutic target in leukemias. For this reason, telomerase-based immunotherapy is analyzed in the fight against leukemias, leveraging the immune system to eliminate leukemia cells with uncontrolled proliferation. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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18 pages, 7292 KiB  
Review
Molecular Tactics of Biocontrol Fungi to Hack Plant Immunity for Successful Host Colonization—A Focus on Trichoderma Fungi
by Yingfen Yang, Meiwei Zhao, Guotao Li, Ying Wang, Qingqing Shen, Jun Yang, Tahani A. Y. Asseri, Yanjun Wang, Min Guo and Waqar Ahmed
Microorganisms 2025, 13(6), 1251; https://doi.org/10.3390/microorganisms13061251 - 28 May 2025
Viewed by 604
Abstract
To play a role effectively, biocontrol fungi must fight against plant immune response and establish a symbiotic interaction with their host. After successfully colonizing the host plant, the biocontrol fungi may deliver beneficial effects related to plant health and resistance against phytopathogens. These [...] Read more.
To play a role effectively, biocontrol fungi must fight against plant immune response and establish a symbiotic interaction with their host. After successfully colonizing the host plant, the biocontrol fungi may deliver beneficial effects related to plant health and resistance against phytopathogens. These fungi use a variety of tactics to bypass the host immune response, including the production of effector proteins, miRNA interference, manipulation of host defense mechanisms, and others. In this review article, we discussed these strategies of biocontrol fungi based on recent findings. These methods enable the fungi to escape the plant’s intrinsic immunity and finely adjust the plant’s defense signaling cascades. Additionally, we discussed the importance of the physical barrier in the form of host cell walls and elucidated how biocontrol fungi use a combination of mechanical and enzymatic tactics to overcome this obstacle. Given the evolving comprehensions from molecular biology, genomics, and ecology, this review article highlights the prospective for a holistic, interdisciplinary approach to improve our understanding of the biocontrol mechanism. Full article
(This article belongs to the Special Issue Plant–Fungal Interactions in Biocontrol of Plant Diseases)
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55 pages, 2227 KiB  
Review
Is Green Hydrogen an Environmentally and Socially Sound Solution for Decarbonizing Energy Systems Within a Circular Economy Transition?
by Patrizia Ghisellini, Renato Passaro and Sergio Ulgiati
Energies 2025, 18(11), 2769; https://doi.org/10.3390/en18112769 - 26 May 2025
Cited by 3 | Viewed by 802
Abstract
Green hydrogen (GH2) is expected to play an important role in future energy systems in their fight against climate change. This study, after briefly recalling how GH2 is produced and the main steps throughout its life cycle, analyses its current [...] Read more.
Green hydrogen (GH2) is expected to play an important role in future energy systems in their fight against climate change. This study, after briefly recalling how GH2 is produced and the main steps throughout its life cycle, analyses its current development, environmental and social impacts, and a series of case studies from selected literature showing its main applications as fuel in transportation and electricity sectors, as a heat producer in high energy intensive industries and residential and commercial buildings, and as an industrial feedstock for the production of other chemical products. The results show that the use of GH2 in the three main areas of application has the potential of contributing to the decarbonization goals, although its generation of non-negligible impacts in other environmental categories requires attention. However, the integration of circular economy (CE) principles is important for the mitigation of these impacts. In social terms, the complexity of the value chain of GH2 generates social impacts well beyond countries where GH2 is produced and used. This aspect makes the GH2 value chain complex and difficult to trace, somewhat undermining its renewability claims as well as its expected localness that the CE model is centred around. Full article
(This article belongs to the Collection Energy-Efficient Chemistry)
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24 pages, 4070 KiB  
Article
The Evaluation of a Large-Scale Flood-Fighting Exercise: Capacity Development of Flood Fighting in Mie Prefecture, Japan
by Toshikazu Tokioka and Jun Kawaguchi
Water 2025, 17(11), 1564; https://doi.org/10.3390/w17111564 - 22 May 2025
Viewed by 549
Abstract
The importance of flood fighting is becoming increasingly apparent worldwide in the context of climate change. In light of the often-limited conditions and resources available for the deployment of military and professional rescue teams in emergencies, flood-fighting corps that help protect communities from [...] Read more.
The importance of flood fighting is becoming increasingly apparent worldwide in the context of climate change. In light of the often-limited conditions and resources available for the deployment of military and professional rescue teams in emergencies, flood-fighting corps that help protect communities from floods have been organized by community members in numerous regions. This study aims to evaluate the extent to which the capabilities of flood-fighting corps and other participating organizations were developed through a field exercise conducted in Japan involving 55 relevant organizations and 1025 participants. The requisite data were obtained through structured in-person interviews with 18 participants playing key roles in the exercise, who were questioned about the effects of the exercise. The findings showed that the exercise achieved three principal outcomes: (1) the strengthening of inter-organizational collaboration, (2) the learning of authentic capabilities by simulating a real-world flood-fighting environment, and (3) an increase in public awareness of flood fighting through extensive public relations efforts. Furthermore, this study concluded that the national government should take a leading role in organizing such large-scale exercises involving multiple organizations with diverse cultural backgrounds and responsibilities in order to generate these outcomes. Full article
(This article belongs to the Special Issue Advances in Crisis and Risk Management of Extreme Floods)
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28 pages, 9306 KiB  
Review
Repurposing Sigma-1 Receptor-Targeting Drugs for Therapeutic Advances in Neurodegenerative Disorders
by Kiarash Eskandari, Sara-Maude Bélanger, Véronik Lachance and Saïd Kourrich
Pharmaceuticals 2025, 18(5), 700; https://doi.org/10.3390/ph18050700 - 9 May 2025
Cited by 1 | Viewed by 1467
Abstract
Neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, due to their multifaced and complicated nature, remain uncurable and impose substantial financial and human burdens on society. Therefore, developing new innovative therapeutic strategies is vital. In this context, drug repurposing has emerged as [...] Read more.
Neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, due to their multifaced and complicated nature, remain uncurable and impose substantial financial and human burdens on society. Therefore, developing new innovative therapeutic strategies is vital. In this context, drug repurposing has emerged as a promising avenue to expedite the development of treatments for these challenging conditions. One particularly compelling target in this regard is the chaperone protein sigma-1 receptor (S1R), which has garnered significant attention for its neuroprotective properties. Interestingly, several medications, including fluvoxamine (an antidepressant), dextromethorphan (a cough suppressant), and amantadine (an antiviral), which were initially developed for unrelated indications, have shown encouraging results in neurodegenerative therapy through S1R activation. These findings suggest that existing drugs in pharmacopeias can play an essential role in alleviating neurodegenerative symptoms by modulating S1R, thereby offering a faster route and cost-effective path to clinical applications compared to the de novo development of entirely new compounds. Furthermore, as a synergistic benefit, combining S1R-targeting drugs with other therapeutic agents may also improve treatment efficacy. In this review, we highlight key repurposed drugs targeting S1R and explore their mechanisms of action, shedding light on their emerging therapeutic potential in the fight against neurodegeneration. Full article
(This article belongs to the Special Issue Current Advances in Therapeutic Potential of Sigma Receptor Ligands)
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12 pages, 2896 KiB  
Article
An Untargeted Gas Chromatography–Ion Mobility Spectrometry Approach for the Geographical Origin Evaluation of Dehydrated Apples
by Giuseppe Sammarco, Chiara Dall’Asta and Michele Suman
Processes 2025, 13(5), 1373; https://doi.org/10.3390/pr13051373 - 30 Apr 2025
Viewed by 407
Abstract
Gas chromatography–ion mobility spectrometry (GC-IMS) is an interesting candidate to face geographical origin declaration fraud in dehydrated apple samples. It allows the collection of the peculiar fingerprints of the analysed samples with the bi-dimensional separation of volatile molecules, based on their polarity and [...] Read more.
Gas chromatography–ion mobility spectrometry (GC-IMS) is an interesting candidate to face geographical origin declaration fraud in dehydrated apple samples. It allows the collection of the peculiar fingerprints of the analysed samples with the bi-dimensional separation of volatile molecules, based on their polarity and their dimension and shape. It represents a rapid, cost-effective, and sensitive solution for food authenticity issues. A design of experiment (DoE) led to robust sampling, taking into account different factors, such as harvesting year, the presence of peel, variety. The sample preparation was limited as it required only the milling of the dehydrated apple dices before the analysis. The GC-IMS analytical method permitted us to obtain of a 3D graph in 11 min, and the multivariate statistical analysis returned a clear separation between Italian and non-Italian (French, Chinese, Hungarian, Polish) samples, considering both unsupervised and supervised approaches. The statistical model, created employing a training set, was applied on a further test set, with a good overall performance. Thus, GC-IMS could play a relevant role as a tool to prevent/fight false origin declaration frauds and also, potentially, other kinds of food authenticity and safety frauds. Full article
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19 pages, 3185 KiB  
Article
Non-Linear Modeling of Immune System Activation and Lymph Flow Dynamics
by Ştefan Cǎtǎlin Petrescu, Ruxandra Ioana Cipu, Andra Cristiana Maria-Fulaşu and Elena Corina Cipu
Appl. Sci. 2025, 15(9), 4972; https://doi.org/10.3390/app15094972 - 30 Apr 2025
Viewed by 352
Abstract
The immune system is a vital defense network within the body, where lymph and lymph nodes play pivotal roles. Lymph is a transparent fluid containing white blood cells, specifically lymphocytes, which circulate through the lymphatic system, rapidly multiplying to fight viruses and bacteria. [...] Read more.
The immune system is a vital defense network within the body, where lymph and lymph nodes play pivotal roles. Lymph is a transparent fluid containing white blood cells, specifically lymphocytes, which circulate through the lymphatic system, rapidly multiplying to fight viruses and bacteria. Lymph nodes function as filters, capturing and eliminating infections and abnormal cells found in the lymphatic fluid prior to its reentry into the circulatory system. A thorough meta-analysis of research publications in the topic is conducted utilizing Bibliometrix to comprehensively assess the current literature. The paper is centered on understanding the intricate relationship between interferons, dendritic cells, and macrophages in the lymphatic system during hepatitis virus infection. A nonlinear model for the development of the virus is used, together with the initial conditions, for a much better understanding of a hepatitis-C infection. The associated Cauchy problem is numerically solved and graphs are depicted. The interpretation of the figures explains the dynamics of interferons, dendritic cells, and macrophages as well as their interaction with other factors. By adopting an interdisciplinary approach, this study offers fresh perspectives and uncovers new research areas to better comprehend and battle hepatitis virus infections. Full article
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13 pages, 9470 KiB  
Article
The Binding of Brazilin from C. sappan to the Full-Length SARS-CoV-2 Spike Proteins
by Phonphiphat Bamrung, Borvornwat Toviwek, Firdaus Samsudin, Phoom Chairatana, Peter John Bond and Prapasiri Pongprayoon
Int. J. Mol. Sci. 2025, 26(9), 4100; https://doi.org/10.3390/ijms26094100 - 25 Apr 2025
Viewed by 564
Abstract
The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global issue since 2019. The prominent characteristic of SARS-CoV-2 is the presence of the spike (S) protein protruding from the virus particle envelope. The S protein [...] Read more.
The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global issue since 2019. The prominent characteristic of SARS-CoV-2 is the presence of the spike (S) protein protruding from the virus particle envelope. The S protein is a major drug and vaccine target because it initiates the key step in infection. Medicinal herbs are a potential treatment option to enhance immunity to fight viral infections. Caesalpinia sappan L. has been reported to display promising anti-viral activities. Specifically, brazilin (BRA), a major bioactive compound in C. sappan, was reported to play a role in inhibiting viral infection. Thus, the ability of BRA as a COVID-19 treatment was tested. The S protein was used as the BRA target of this work. Understanding the binding mechanism of BRA to the S protein is crucial for future utilisation of C. sappan as a COVID-19 treatment or other coronavirus-caused pandemics. Here, we performed molecular docking of BRA onto the S protein receptor binding domain (RBD) and multimerisation (MM) pockets. Molecular dynamics (MD) simulations were conducted to study the stability of binding to glycosylated and non-glycosylated S protein constructs. BRA can bind to the Receptor-binding motif (RBM) on an RBD surface stably; however, it is too large to fit into the MM pocket, resulting in dissociation. Nonetheless, BRA is bound by residues near the S1/S2 interface. We found that glycosylation has no effect on BRA binding, as the proposed binding site is far from any glycans. Our results thus indicate that C. sappan may act as a promising preventive and therapeutic alternative for COVID-19 treatment. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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25 pages, 1135 KiB  
Review
Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology
by Moon Nyeo Park, Myoungchan Kim, Soojin Lee, Sojin Kang, Chi-Hoon Ahn, Trina Ekawati Tallei, Woojin Kim and Bonglee Kim
Antioxidants 2025, 14(5), 501; https://doi.org/10.3390/antiox14050501 - 22 Apr 2025
Viewed by 1448
Abstract
Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that [...] Read more.
Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP. These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8+ T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS–miRNA–exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output. In addition, we analyze the therapeutic relevance of natural products and herbal compounds—such as curcumin, resveratrol, and ginsenosides—which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics. We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation. Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer. Full article
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14 pages, 2354 KiB  
Article
Effectiveness of Helicopters in Fighting Forest Fires in Türkiye: A Data Envelopment Analysis Approach
by Melih Yıldız, Ozan Öztürk and Tuğba Akbıyık
Fire 2025, 8(4), 156; https://doi.org/10.3390/fire8040156 - 18 Apr 2025
Viewed by 1293
Abstract
This study aims to evaluate the effectiveness of helicopters in fighting forest fires in Türkiye. The increasing frequency and severity of forest fires, especially with climate change, require more effective aerial response methods. Helicopters play a critical role due to their operational advantages, [...] Read more.
This study aims to evaluate the effectiveness of helicopters in fighting forest fires in Türkiye. The increasing frequency and severity of forest fires, especially with climate change, require more effective aerial response methods. Helicopters play a critical role due to their operational advantages, such as maneuverability, rapid access, and water-carrying capacity. In this study, the types of helicopters used in Türkiye are analyzed, and their operational efficiency is evaluated using Data Envelopment Analysis (DEA). The results reveal that certain models show high efficiency, but some helicopters have room for improvement in terms of fuel consumption and technical performance. A balanced use of both Bambi Bucket and internal water tank systems in fighting forest fires in Türkiye and investing in domestic production is recommended. Full article
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34 pages, 5499 KiB  
Review
Targeting Siderophore Biosynthesis to Thwart Microbial Growth
by Beatriz M. Rocha, Eugénia Pinto, Emília Sousa and Diana I. S. P. Resende
Int. J. Mol. Sci. 2025, 26(8), 3611; https://doi.org/10.3390/ijms26083611 - 11 Apr 2025
Viewed by 1229
Abstract
The growing threat of antibiotic resistance has made treating bacterial and fungal infections increasingly difficult. With the discovery of new antibiotics slowing down, alternative strategies are urgently needed. Siderophores, small iron-chelating molecules produced by microorganisms, play a crucial role in iron acquisition and [...] Read more.
The growing threat of antibiotic resistance has made treating bacterial and fungal infections increasingly difficult. With the discovery of new antibiotics slowing down, alternative strategies are urgently needed. Siderophores, small iron-chelating molecules produced by microorganisms, play a crucial role in iron acquisition and serve as virulence factors in many pathogens. Because iron is essential for microbial survival, targeting siderophore biosynthesis and transport presents a promising approach to combating drug-resistant infections. This review explores the key genetic and biochemical mechanisms involved in siderophore production, emphasizing potential drug targets within these pathways. Three major biosynthetic routes are examined: nonribosomal peptide synthetase (NRPS)-dependent, polyketide synthase (PKS)-based, and NRPS-independent (NIS) pathways. Additionally, microbial iron uptake mechanisms and membrane-associated transport systems are discussed, providing insights into their role in sustaining pathogenic growth. Recent advances in inhibitor development have shown that blocking critical enzymes in siderophore biosynthesis can effectively impair microbial growth. By disrupting these pathways, new antimicrobial strategies can be developed, offering alternatives to traditional antibiotics and potentially reducing the risk of resistance. A deeper understanding of siderophore biosynthesis and its regulation not only reveals fundamental microbial processes but also provides a foundation for designing targeted therapeutics. Leveraging these insights could lead to novel drugs that overcome antibiotic resistance, offering new hope in the fight against persistent infections. Full article
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