Curr Genomics. 2025;26(2):81-94. doi: 10.2174/0113892029325491240919151045. Epub 2024 Oct 1.

ABSTRACT

Analyzing prokaryotic codon usage trends has become a crucial topic of study with significant ramifications for comprehending microbial genetics, classification, evolution, and the control of gene expression. This review study explores the numerous facets of prokaryotic codon usage patterns, looking at different parameters like habitat and lifestyle across broad groups of prokaryotes by emphasizing the role of codon reprogramming in adaptive strategies and its integration into systems biology. We also explored the numerous variables driving codon usage bias, including natural selection, mutation, horizontal gene transfer, codon-anticodon interaction, and genomic composition in prokaryotes through a thorough study of current literature. Furthermore, a special session on codon usage on pathogenic prokaryotes and the role of codon usage in the phylogeny of prokaryotes has been discussed. We also looked at the various software and indices that have been recently applied to prokaryotic genomes. The promising directions that lay ahead to map the future of codon usage research on prokaryotes have been emphasized. Codon usage variations across prokaryotic communities could be better understood by combining environmental, metagenomic, and system biology approaches.

PMID:40433443 | PMC:PMC12105230 | DOI:10.2174/0113892029325491240919151045

Vaccines (Basel). 2025 May 18;13(5):537. doi: 10.3390/vaccines13050537.

ABSTRACT

Objectives: The COVID-19 pandemic has brought mRNA vaccines to the forefront due to their widespread use. In this study, we explored the potential advantages of the self-amplifying mRNA (saRNA) vaccine over conventional mRNA vaccines. Methods: Initially, we optimized lipid nanoparticle formulations and employed dT20 affinity chromatography purification to improve the intracellular expression of saRNA. Subsequently, we demonstrated that saRNA exhibited sustained expression for up to one month, both in vitro and in vivo, in contrast to mRNA. Finally, we developed a saRNA-based COVID-19 vaccine and achieved superior immune protection in mice compared to mRNA vaccine by co-delivering the B18R-encoding mRNA. Results: The co-delivery of B18R-mRNA with the saRNA vaccine significantly enhanced neutralizing antibody responses, outperforming those induced by the mRNA vaccine alone. This co-delivery strategy effectively regulated the early innate immune activation triggered by saRNA, facilitating a more robust adaptive immune response. Conclusions: The optimization strategies we used in this study highlight the potential of saRNA vaccines to offer stronger and more durable immune protection. The insights gained from this study not only promote the advancement of saRNA vaccine development but also provide practical guidance for their broader application in the fight against infectious diseases.

PMID:40432146 | DOI:10.3390/vaccines13050537

Vaccines (Basel). 2025 May 4;13(5):496. doi: 10.3390/vaccines13050496.

ABSTRACT

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Conventional therapies are frequently limited by tumor heterogeneity and the immunosuppressive tumor microenvironment (TME). Dendritic cells (DCs), central to orchestrating antitumor immunity, have become key targets for HCC immunotherapy. This review examines the biological functions of DC subsets (cDC1, cDC2, pDC, and moDC) and their roles in initiating and modulating immune responses against HCC. We detail the mechanisms underlying DC impairment within the TME, including suppression by regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs). Additionally, we discuss novel DC-based therapeutic strategies, such as DC-based vaccines designed to enhance antigen presentation and T cell activation. Combining DC vaccines with immune checkpoint inhibitors (ICIs), including PD-1/PD-L1 and CTLA-4 blockers, demonstrates synergistic effects that can overcome immune evasion and improve clinical outcomes. Despite progress, challenges related to DC subset heterogeneity, TME complexity, and patient variability require the further optimization and personalization of DC-based therapies. Future research should focus on refining these strategies, leveraging advanced technologies like genomic profiling and artificial intelligence, to maximize therapeutic efficacy and revolutionize HCC treatment. By restoring DC function and reprogramming the TME, DC-based immunotherapy holds immense potential to transform the management of HCC and improve patient survival.

PMID:40432108 | DOI:10.3390/vaccines13050496

Vet Sci. 2025 May 16;12(5):485. doi: 10.3390/vetsci12050485.

ABSTRACT

Hemoglobin-based oxygen carriers (HBOCs) represent a promising alternative to traditional blood transfusions, offering the advantages of extended shelf life and avoiding blood compatibility limitations and infection risks. Positive effects of hemoglobin-based oxygen carriers (HBOCs) on hemorrhagic shock have been researched across various animal species, including swine, rats, rabbits, guinea pigs, and dogs. As previously described, HBOCs based on ovine hemoglobin display better efficiency in the context of hemorrhagic shock compared to those based on the more commonly used bovine hemoglobin. This was evidenced through higher survival rates and more favorable histopathological and immunological outcomes. The vascular effects of ovine hemoglobin polymerized with glutaraldehyde exposure included the absence of hypertension, minimal endothelial damage with slight alterations in inducible nitric oxide synthase (iNOS), and reduced vascular inflammation mediated by interleukin-10 (IL-10). Ovine hemoglobin has emerged as a particularly promising raw material for the development of HBOCs, surpassing bovine and human hemoglobin due to its advantages in availability and efficacy. Furthermore, reducing oxidative stress by polymerizing hemoglobin with glutaraldehyde is most effective with ovine hemoglobin compared to bovine hemoglobin. This study evaluates the effectiveness of ovine hemoglobin polymerized with glutaraldehyde in managing hemorrhagic shock in rabbits, with a focus on its ability to maintain blood pressure, support oxygen transport, and assess potential systemic and oxidative responses. Fifteen adult New Zealand white rabbits, divided into three equal groups, were included in this study: a negative control group transfused with colloid solutions, a positive control group treated with autotransfusion, and a group receiving HBOCs. All groups underwent a hemorrhagic shock protocol, with 40% of their total blood volume withdrawn under deep anesthesia, followed by transfusions 30 min later. Vital parameters, including invasive arterial blood pressure, heart rate, and end-tidal CO2, were measured throughout the experimental procedures. Arterial blood gas samples were collected before the procedures, after hemorrhagic shock induction, and at the conclusion of the transfusion. In summary, HBOCs offer a promising solution for oxygen delivery, but their effects on blood chemistry, particularly CO2 and lactate levels, must be considered. Although no direct oxygenation issues were observed in experimental models, elevated CO2 levels and the interference of HBOCs with lactate measurements emphasize the importance of vigilant clinical monitoring. Polymerized hemoglobin provides a non-nephrotoxic alternative, but challenges persist in preventing nitric oxide scavenging and ensuring effective oxygen delivery.

PMID:40431578 | DOI:10.3390/vetsci12050485

Microorganisms. 2025 May 15;13(5):1136. doi: 10.3390/microorganisms13051136.

ABSTRACT

Bacillus cereus poses a persistent challenge for human milk banks (HMBs) due to its ability to survive Holder pasteurization (HoP; 62.5 °C for 30 min). To ensure neonatal safety, any milk found to be contaminated post-HoP must be discarded, which impacts milk supply and adds to the operational demands of HMBs. In this study, we analyzed 688 B. cereus isolates from human milk (pre- and post-HoP), as well as from patient and environmental sources, to investigate human milk contamination by B. cereus at a Canadian HMB. Despite the limited temporal and geographic scope of the collection, the isolates exhibited remarkable genomic diversity, comparable to global B. cereus collections. Phylogenetic analysis at the core genome level revealed no clear clustering by isolate source, suggesting multifactorial pathways of B. cereus contamination. Isolates surviving HoP displayed gene variants linked to sporulation and cell wall integrity, suggesting a potential basis for HoP tolerance. Our findings emphasize that while genomic analyses offer major valuable insights, they alone are insufficient to address the complexities of B. cereus contamination in HMBs. Addressing this challenge will require combining genomic tools with robust monitoring systems, improved human milk-handling protocols, and pasteurization strategies better-suited to countering B. cereus resilience.

PMID:40431308 | DOI:10.3390/microorganisms13051136

Microorganisms. 2025 May 12;13(5):1110. doi: 10.3390/microorganisms13051110.

ABSTRACT

Microorganisms play an essential role in the biogeochemical processes of macroalgal cultivation ecosystems by participating in a complex network of interactions, significantly influencing the growth and development of macroalgae. This study used bibliometric analysis and VOSviewer based on Web of Science data to provide an overview by tracing the developmental footprint of the technology. Countries, institutions, authors, keywords, and key phrases were tracked and mapped accordingly. From 1 January 2003 to 31 December 2023, 619 documents by 2516 authors from 716 institutions in 51 countries were analyzed. Keyword co-occurrence network analysis revealed five main areas of research on microbes in macroalgal cultivation ecosystems: (1) identification of microbial species and functional genes, (2) biogeochemical cycling of carbon in microbial communities, (3) microbial influences on macroalgae growth and development, (4) bioactivities, and (5) studies based on database. Thematic evolution and map research emphasized the centrality of microbial diversity research in this direction. Over time, the research hotspots and the core scientific questions of the microorganisms in the macroalgal cultivation ecosystems have evolved from single-organism interactions to the complex dynamics of microbial communities. The application of high-throughput techniques had become a hotspot, and the adoption of systems biology approaches had further facilitated the integrated analysis of microbial community composition and function. Our results provide valuable guidance and information for future researches on algal-bacterial interactions and microbe-driven carbon cycling in coastal ecosystems.

PMID:40431284 | DOI:10.3390/microorganisms13051110

Plants (Basel). 2025 May 20;14(10):1532. doi: 10.3390/plants14101532.

ABSTRACT

Cannabis sativa L. is cultivated for therapeutic and recreational use. Delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) are primarily responsible for its psychoactive and medicinal effects. As the global cannabis industry continues to expand, constant review and optimization of horticultural practices are needed to ensure a reliable harvest and improved crop quality. There is currently uncertainty about the optimal harvest time of C. sativa, i.e., when cannabinoid concentrations are at their highest during inflorescence maturation. At present, growers observe the color transition of stigmas from white to amber as an indicator of harvest time. This research investigates the relationship between stigma color and cannabinoid concentration using liquid chromatography-mass spectrometry (LCMS) and digital image analysis. Additionally, early screening prediction models have also been developed for six cannabinoids using near-infrared (NIR) spectroscopy and LCMS to assist in early cannabinoid determination. Among the genotypes grown, 22 of 25 showed cannabinoid concentration peaks between the third (mostly amber) and fourth (fully amber) stages; however, some genotypes peaked within the first (no amber) and second (some amber) stages. We have determined that the current 'rule of thumb' of harvesting when a cannabis plant is mostly amber is still a useful approximation in most cases; however, studies on individual genotypes should be performed to determine their individual optimal harvest time based on the desired cannabinoid profile or total cannabinoid concentration.

PMID:40431097 | DOI:10.3390/plants14101532

Plants (Basel). 2025 May 12;14(10):1440. doi: 10.3390/plants14101440.

ABSTRACT

Passion fruit (Passiflora edulis), a tropical crop of significant economic value, exhibits temperature-sensitive floral development. Here, we identified 23 TALE transcription factors (PeTALEs) and characterized their roles in floral organogenesis and thermal adaptation. Phylogenetic analysis classified PeTALEs into KNOX and BELL subfamilies, with conserved domain architectures and cis-regulatory elements linked to stress and hormone signaling. Spatiotemporal expression profiling revealed PeTALE21 as a key regulator of corona initiation, while PeTALE17 dominated in later floral stages. Temperature stress assays demonstrated cold-induced upregulation of PeTALE15/16/19/22 and heat-mediated suppression of PeTALE10/18/21. Yeast two-hybrid assays uncovered functional interactions between PeTALE3/16/18/22/23, highlighting a network governing floral thermoresilience. This study provides the first genome-wide analysis of PeTALEs, offering insights for breeding climate-resilient passion fruit varieties.

PMID:40431006 | DOI:10.3390/plants14101440

Pathogens. 2025 Apr 24;14(5):413. doi: 10.3390/pathogens14050413.

ABSTRACT

Citrus black spot (CBS), caused by the fungus Phyllosticta citricarpa, significantly affects citrus fruit marketability and can lead to premature fruit drop. Accurate and reliable detection of this quarantine pathogen is crucial, particularly for asymptomatic plant material. This study evaluated two qPCR assays, the EPPO recommended assay PC and assay Pc-TEF1, based on TEF region, for detecting P. citricarpa through a collaborative test performance study (TPS). DNA from the isolates of Phyllosticta spp. and other fungi was spiked into citrus fruit peel extracts (lemon, orange, and pomelo) and distributed among 13 laboratories. Sample and qPCR assay stability under typical transport conditions was confirmed, although prolonged storage affected Pc-TEF1 assay performance. The assays were assessed based on sensitivity, specificity, reproducibility, and repeatability. Both assays demonstrated high performance, with repeatability and reproducibility exceeding 95%. The PC assay, as expected, detected different related Phyllosticta species, while Pc-TEF1 showed higher specificity for P. citricarpa included in the TPS alone. Additionally, inhibitory effects were observed specifically in the pomelo peel samples, suggesting matrix-dependent variability. This TPS confirms that both PC and Pc-TEF1 qPCR assays are robust. Further evaluation of the qPCR assays would support the selection of the most reliable assays for the detection of P. citricarpa, contributing to the effective management of CBS disease in citrus production and trade.

PMID:40430734 | DOI:10.3390/pathogens14050413

Pharmaceuticals (Basel). 2025 May 12;18(5):712. doi: 10.3390/ph18050712.

ABSTRACT

'Blood stasis' (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (). Similar concepts exist in Traditional Korean Medicine ('Eohyul') and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down ('stasis') of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke.

PMID:40430532 | DOI:10.3390/ph18050712

Pharmaceuticals (Basel). 2025 Apr 23;18(5):613. doi: 10.3390/ph18050613.

ABSTRACT

Background: Oropouche virus (OROV), part of the Peribunyaviridae family, is an emerging pathogen causing Oropouche fever, a febrile illness endemic in South and Central America. Transmitted primarily through midge bites (Culicoides paraensis), OROV has no specific antiviral treatment or vaccine. This study aims to identify host-targeted therapeutics against OROV using computational approaches, offering a potential strategy for sustainable antiviral drug discovery. Methods: Virus-associated host targets were identified using the OMIM and GeneCards databases. The Enrichr and DSigDB platforms were used for drug prediction, filtering compounds based on Lipinski's rule for drug likeness. A protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape 3.10.3 software. Four key host targets-IL10, FASLG, PTPRC, and FCGR3A-were prioritized based on their roles in immune modulation and OROV pathogenesis. Molecular docking simulations were performed using the PyRx software to evaluate the binding affinities of selected small-molecule inhibitors-Acetohexamide, Deptropine, Methotrexate, Retinoic Acid, and 3-Azido-3-deoxythymidine-against the identified targets. Results: The PPI network analysis highlighted immune-mediated pathways such as Fc-gamma receptor signaling, cytokine control, and T-cell receptor signaling as critical intervention points. Molecular docking revealed strong binding affinities between the selected compounds and the prioritized targets, suggesting their potential efficacy as host-targeting antiviral candidates. Acetohexamide and Deptropine showed strong binding to multiple targets, indicating broad-spectrum antiviral potential. Further in vitro and in vivo validations are needed to confirm these findings and translate them into clinically relevant treatments. Conclusions: This study highlights the potential of using computational approaches to identify host-targeted therapeutics for Oropouche virus (OROV). By targeting key host proteins involved in immune modulation-IL10, FASLG, PTPRC, and FCGR3A-the selected compounds, Acetohexamide and Deptropine, demonstrate strong binding affinities, suggesting their potential as broad-spectrum antiviral candidates. Further experimental validation is needed to confirm their efficacy and potential for clinical application, offering a promising strategy for sustainable antiviral drug discovery.

PMID:40430433 | DOI:10.3390/ph18050613

Molecules. 2025 May 21;30(10):2251. doi: 10.3390/molecules30102251.

ABSTRACT

Although the global incidence of tuberculosis has declined in recent years, tuberculosis remains a major global public health challenge. The Mycobacterium tuberculosis complex (MTBC) including M. tuberculosis, M. bovis, M. microti, etc., is the deadliest Mycobacterium spp. that needs more attention. Research on M. microti is significant as it is a zoonotic pathogen that can spread between animals and humans. By exploring the function of a transglutaminase in M. microti (MmTG), which is widely distributed in Mycobacterium and other species, a potential cytotoxic effector has been characterized. MmTG inhibits cell proliferation by inducing the phosphorylation of RIPK1 (receptor-interacting serine/threonine-protein kinase 1) and the Cys159 of MmTG is the highly conserved residue related to its cytotoxicity. Understanding MmTG and its homologs can provide more insights into the pathogenic mechanisms of mycobacteria and contribute to the development of more effective therapeutic strategies against mycobacterial infections.

PMID:40430423 | DOI:10.3390/molecules30102251

Life (Basel). 2025 May 17;15(5):799. doi: 10.3390/life15050799.

ABSTRACT

Genomic instability has been increasingly recognized over the past decade as a fundamental driver of cancer initiation and progression, largely owing to its association with specific genes and cellular mechanisms that offer therapeutic potential. However, a comprehensive molecular framework that captures the interconnected processes underlying this phenomenon remains elusive. In this study, we focused on polo-like kinase 1 (PLK1), a key cell cycle regulator frequently overexpressed in diverse human tumors, to reconstruct a regulatory network that consolidates pre-existing biological knowledge exclusively related to pathways involved in genome stability maintenance and cancer. The resulting model integrates nine biological processes, 1030 reactions, and 716 molecular species to form a literature-supported network in which PLK1 serves as a central regulatory node. However, rather than depicting an isolated PLK1-centric system, this network reflects a broader and more complex architecture of interrelated genomic instability mechanisms. As expected, the simulations reproduced known behaviors associated with PLK1 dysregulation, reinforcing the well-established role of the kinase in genome destabilization. Importantly, this model also enables the exploration of additional, less-characterized dynamics, including the potential involvement of genes such as kif2c, incenp, and other regulators of chromosomal segregation and DNA repair, which appear to contribute to instability events downstream of PLK1. While these findings are grounded in mechanistic simulations and require further experimental validation, gene expression and survival analyses across tumor types support their clinical relevance by linking them to poor prognosis in specific cancers. Overall, the model provides a systemic and adaptable foundation for studying PLK1-related genomic instability, enabling both the reinforcement of known mechanisms and discovery of candidate genes and circuits that may drive tumorigenesis through compromised genome integrity across distinct cancer contexts.

PMID:40430225 | DOI:10.3390/life15050799

Life (Basel). 2025 Apr 29;15(5):723. doi: 10.3390/life15050723.

ABSTRACT

The topic of this work is gene expression and its score according to various factors analyzed globally using machine learning techniques. The expression score (ES) of genes characterizes their activity and, thus, their importance for cellular processes. This may depend on many different factors (attributes). To find the most important classifier, a machine learning classifier (random forest) was selected, trained, and optimized on the Waikato Environment for Knowledge Analysis WEKA platform, resulting in the most accurate attribute-dependent prediction of the ES of Saccharomyces cerevisiae genes. In this way, data from the Saccharomyces Genome Database (SGD), presenting ES values corresponding to a wide spectrum of attributes, were used, revised, classified, and balanced, and the significance of the considered attributes was evaluated. In this way, the novel random forest model indicates the most important attributes determining classes of low, moderate, and high ES. They cover both the experimental conditions and the genetic, physical, statistical, and logistic features. During validation, the obtained model could classify the instances of a primary unknown test set with a correctness of 84.1%.

PMID:40430151 | DOI:10.3390/life15050723

Int J Mol Sci. 2025 May 9;26(10):4525. doi: 10.3390/ijms26104525.

ABSTRACT

Graphene-based materials (GBMs) have shown significant promise in cancer therapy due to their unique physicochemical properties, biocompatibility, and ease of functionalization. Their ability to target solid tumors, penetrate the tumor microenvironment (TME), and act as efficient drug delivery platforms highlights their potential in nanomedicine. However, the complex and dynamic nature of the TME, characterized by metabolic heterogeneity, immune suppression, and drug resistance, poses significant challenges to effective cancer treatment. GBMs offer innovative solutions by enhancing tumor targeting, facilitating deep tissue penetration, and modulating metabolic pathways that contribute to tumor progression and immune evasion. Their functionalization with targeting ligands and biocompatible polymers improves their biosafety and specificity, while their ability to modulate immune cell interactions within the TME presents new opportunities for immunotherapy. Given the role of metabolic reprogramming in tumor survival and resistance, GBMs could be further exploited in metabolism-targeted therapies by disrupting glycolysis, mitochondrial respiration, and lipid metabolism to counteract the immunosuppressive effects of the TME. This review focuses on discussing research studies that design GBM nanocomposites with enhanced biodegradability, minimized toxicity, and improved efficacy in delivering therapeutic agents with the intention to reprogram the TME for effective anticancer therapy. Additionally, exploring the potential of GBM nanocomposites in combination with immunotherapies and metabolism-targeted treatments could lead to more effective and personalized cancer therapies. By addressing these challenges, GBMs could play a pivotal role in overcoming current limitations in cancer treatment and advancing precision oncology.

PMID:40429669 | DOI:10.3390/ijms26104525

J Clin Med. 2025 May 13;14(10):3406. doi: 10.3390/jcm14103406.

ABSTRACT

Objective: This study evaluates whether one-year changes in physical activity (PA), pain intensity, and quality of life (QOL) after exercise therapy and education are larger than normal fluctuations over time in individuals with knee osteoarthritis. Method: Patients with knee osteoarthritis participating in the Good Life with Osteoarthritis in Denmark (GLA:D®) exercise therapy and education program (n = 7603) and participants from the Osteoarthritis Initiative (OAI) who received no specific treatment (n = 1156) were included. PA was measured using the UCLA PA scale (1-10) in the GLA:D® group and the PASE (0-531) in the OAI group. PASE scores were mapped to the UCLA distribution. Pain intensity was measured using a standardized visual analog scale (VAS, 0-100), and QOL was assessed via the KOOS QOL scale (0-100). Changes were categorized as increased, maintained, and decreased. To ensure comparability between GLA:D® and OAI participants, we used entropy balancing, considering the covariables age, gender, BMI, depression, employment status, and our outcome variables at baseline. Results: At one year, 41% of GLA:D® participants showed increased PA compared to 38% in the balanced OAI group (p = 0.015). Pain intensity decreased by ≥20 mm on the VAS in 39% of GLA:D® and 27% of OAI participants (p < 0.001). QOL improved by ≥ 10 mm on the KOOS scale in 48% of GLA:D® and 40% of OAI participants (p < 0.001). Additionally, for PA, pain, and QOL, 6%, 13%, and 7% more patients in the control group experienced worsening in these outcomes, respectively. Conclusions: Twelve percent more participants experienced clinically relevant pain reductions in the GLA:D® group compared to OAI participants, and 3% and 8% more reported improvements in PA and QOL, respectively. Additionally, more patients in the control group experienced worsening in these outcomes. These differences indicate that clinically relevant pain improvements following exercise therapy and education may exceed normal fluctuations in patients with knee osteoarthritis.

PMID:40429401 | DOI:10.3390/jcm14103406

Genes (Basel). 2025 Apr 28;16(5):515. doi: 10.3390/genes16050515.

ABSTRACT

BACKGROUND/OBJECTIVES: Rhamnolipids (RLs) are biosurfactants with significant industrial and environmental potential, which physicochemical properties depend greatly on their fatty acyl chain composition. This study investigated the impact of genetically modulating the fatty acid synthesis genes fabA and fabZ on RL composition and functionality in Pseudomonas aeruginosa PAO1.

METHODS AND RESULTS: Using temperature-sensitive mutants and suppressor strains for these essential genes, we successfully engineered RLs with altered fatty acyl chain lengths and saturation levels. LC-MS/MS analyses showed that deletion and overexpression of fabA and fabZ significantly shifted RL fatty acid profiles. Functional analyses indicated that these structural changes markedly influenced RL emulsification activity and critical micelle concentration (CMC).

CONCLUSIONS: These findings demonstrate the feasibility of optimizing RL properties through targeted genetic manipulation, offering valuable insights for designing customized biosurfactants for diverse industrial and environmental applications.

PMID:40428336 | DOI:10.3390/genes16050515

Bioengineering (Basel). 2025 Apr 29;12(5):469. doi: 10.3390/bioengineering12050469.

ABSTRACT

Bacteriophages, with their distinctive ability to selectively target host bacteria, stand out as a compelling tool in the realm of drug and gene delivery. Their assembly from proteins and nucleic acids, coupled with their modifiable and biologically unique properties, enables them to serve as efficient and safe delivery systems. Unlike conventional nanocarriers, which face limitations such as non-specific targeting, cytotoxicity, and reduced transfection efficiency in vivo, engineered phages exhibit promising potential to overcome these hurdles and improve delivery outcomes. This review highlights the potential of bacteriophage-based systems as innovative and efficient systems for delivering therapeutic agents. It explores strategies for engineering bacteriophage, categorizes the principal types of phages employed for drug and gene delivery, and evaluates their applications in disease therapy. It provides intriguing details of the use of natural and engineered phages in the therapy of diseases such as cancer, bacterial and viral infections, veterinary diseases, and neurological disorders, as well as the use of phage display technology in generating monoclonal antibodies against various human diseases. Additionally, the use of CRISPR-Cas9 technology in generating genetically engineered phages is elucidated. Furthermore, it provides a critical analysis of the challenges and limitations associated with phage-based delivery systems, offering insights for overcoming these obstacles. By showcasing the advancements in phage engineering and their integration into nanotechnology, this study underscores the potential of bacteriophage-based delivery systems to revolutionize therapeutic approaches and inspire future innovations in medicine.

PMID:40428088 | DOI:10.3390/bioengineering12050469

Biomolecules. 2025 May 2;15(5):656. doi: 10.3390/biom15050656.

ABSTRACT

KIF1A is a neuron-specific kinesin motor responsible for intracellular transport along axons. Pathogenic KIF1A mutations cause KIF1A-associated neurological disorders (KAND), a spectrum of severe neurodevelopmental and neurodegenerative conditions. While individual KIF1A mutations have been studied, how different substitutions at the same residue affect motor function and disease progression remains unclear. Here, we systematically examine the molecular and clinical consequences of mutations at three key motor domain residues-R216, R254, and R307-using single-molecule motility assays and genotype-phenotype associations. We find that different substitutions at the same residue produce distinct molecular phenotypes, and that homodimeric mutant motor properties correlate with developmental outcomes. In addition, we present the first analysis of heterodimeric KIF1A motors-mimicking the heterozygous context in patients-and demonstrate that while heterodimers retain substantial motility, their properties are less predictive of clinical severity than homodimers. These results highlight the finely tuned mechanochemical properties of KIF1A and suggest that dysfunctional homodimers may disproportionately drive the diverse clinical phenotypes observed in KAND. By establishing residue-specific genotype-phenotype relationships, this work provides fundamental insights into KAND pathogenesis and informs targeted therapeutic strategies.

PMID:40427549 | DOI:10.3390/biom15050656

Animals (Basel). 2025 May 19;15(10):1472. doi: 10.3390/ani15101472.

ABSTRACT

Rumen acidosis is a widespread digestive disorder in livestock, causing inflammation and lowering animal performance. Unraveling its molecular mechanisms is vital for improving cattle health and welfare. Circular RNAs (circRNAs) are noncoding RNAs functioning as miRNA or protein sponges. This study employed high-throughput RNA sequencing to identify differentially expressed (DE) circRNAs in subacute rumen acidosis (SARA) in Holstein cattle, revealing 65 DE-circRNAs. We constructed a competitive endogenous RNA (ceRNA) network comprising 57 circRNAs, 14 miRNAs, and 22 mRNAs. Key hub nodes included circRNAs (8:69996068-69996853, 16:2614111-2615445, 5:109525933-109531380, 20:63115665-63116774), miRNAs (bta-miR-146b, bta-miR-181a, bta-miR-223, bta-miR-130b), and mRNAs (SLC2A3, SOCS3, DLC1, ARRDC4). Examination of hub circRNA host genes identified 30 DE transcription factors (TFs). Functional and pathway enrichment analysis pinpointed inflammation and immune response pathways, such as NF-kappa B and TNF signaling. This pioneering study offers the first circRNA expression profile and ceRNA network in SARA cattle, indicating circRNAs' role in inflammation regulation, thus enhancing our understanding of SARA's systems biology and potential treatment strategies.

PMID:40427349 | DOI:10.3390/ani15101472