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13 pages, 3095 KiB  
Article
Uterine Microbiota Composition in Dairy Cows with Different Vaginal Discharge Scores: Suggesting Caviibacter as a Potential Pathogen in Mild Purulent Metritis
by Xiaolei He, Jiajia Wang, Lin Jiang, Xinyu Wang, Yuxing Wang, Yang Liu, Yanping Cheng, Fei Xu and Xiubo Li
Microorganisms 2025, 13(8), 1728; https://doi.org/10.3390/microorganisms13081728 - 24 Jul 2025
Abstract
The uterine microbiota plays a crucial role in maintaining postpartum reproductive health in dairy cows, and its dysregulation is closely associated with uterine diseases. Vaginal discharge characteristics serve as important clinical indicators for assessing uterine status and guiding clinical decision-making. This study employed [...] Read more.
The uterine microbiota plays a crucial role in maintaining postpartum reproductive health in dairy cows, and its dysregulation is closely associated with uterine diseases. Vaginal discharge characteristics serve as important clinical indicators for assessing uterine status and guiding clinical decision-making. This study employed 16S rRNA gene sequencing to analyze uterine microbial diversity in cows with different discharge types. Results revealed significant microbial shifts associated with discharge severity. Notably, Caviibacter was highly enriched (up to 60.25%) in cows with mildly purulent discharge (<50%), suggesting its potential role in early-stage endometritis. In contrast, Fusobacterium and Helcococcus dominated when purulent discharge exceeded 50%, while Bacteroides, Porphyromonas, and Peptostreptococcus prevailed in cows with malodorous or discolored secretions, indicating severe inflammation. This study extends previous findings by uncovering stage-specific microbial transitions and proposing Caviibacter as a potential early biomarker of endometritis. These insights support early diagnosis and targeted interventions, contributing to improved reproductive management and sustainable dairy farming. Full article
(This article belongs to the Special Issue Veterinary Microbiology and Immunology)
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29 pages, 1616 KiB  
Systematic Review
Non-Coding RNAs in Neurodevelopmental Disorders—From Diagnostic Biomarkers to Therapeutic Targets: A Systematic Review
by Katerina Karaivazoglou, Christos Triantos and Ioanna Aggeletopoulou
Biomedicines 2025, 13(8), 1808; https://doi.org/10.3390/biomedicines13081808 - 24 Jul 2025
Abstract
Background: Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), are increasingly recognized as conditions arising from multifaceted interactions among genetic predisposition, environmental exposures, and epigenetic modifications. Among epigenetic mechanisms, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), [...] Read more.
Background: Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), are increasingly recognized as conditions arising from multifaceted interactions among genetic predisposition, environmental exposures, and epigenetic modifications. Among epigenetic mechanisms, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs), have gained attention as pivotal regulators of gene expression during neurodevelopment. These RNA species do not encode proteins but modulate gene expression at transcriptional and post-transcriptional levels, thereby influencing neuronal differentiation, synaptogenesis, and plasticity. Objectives: This systematic review critically examines and synthesizes the most recent findings, particularly in the post-COVID transcriptomic research era, regarding the role of ncRNAs in the pathogenesis, diagnosis, and potential treatment of neurodevelopmental disorders. Methods: A comprehensive literature search was conducted to identify studies reporting on the expression profiles, functional implications, and clinical relevance of ncRNAs in neurodevelopmental disorders, across both human and animal models. Results: Here, we highlight that multiple classes of ncRNAs are differentially expressed in individuals with ASD and ADHD. Notably, specific miRNAs and lncRNAs demonstrate potential as diagnostic biomarkers with high sensitivity and specificity. Functional studies further reveal that ncRNAs actively contribute to pathogenic mechanisms by modulating neuronal gene networks. Conclusions: Emerging experimental data indicate that the exogenous administration of certain ncRNAs may reverse molecular and behavioral phenotypes, supporting their therapeutic promise. These findings broaden our understanding of neurodevelopmental regulation and open new avenues for personalized diagnostics and targeted interventions in clinical neuropsychiatry. Full article
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18 pages, 1717 KiB  
Article
An Immune Assay to Quantify the Neutralization of Oxidation-Specific Epitopes by Human Blood Plasma
by Marija Jelic, Philipp Jokesch, Olga Oskolkova, Gernot Faustmann, Brigitte M. Winklhofer-Roob, Bernd Ullrich, Jürgen Krauss, Rudolf Übelhart, Bernd Gesslbauer and Valery Bochkov
Antioxidants 2025, 14(8), 903; https://doi.org/10.3390/antiox14080903 - 24 Jul 2025
Abstract
Oxidized phospholipids (OxPLs) are increasingly recognized as biologically active lipids involved in various pathologies. Both exposure to pathogenic factors and the efficacy of protective mechanisms are critical to disease development. In this study, we characterized an immunoassay that quantified the total capacity of [...] Read more.
Oxidized phospholipids (OxPLs) are increasingly recognized as biologically active lipids involved in various pathologies. Both exposure to pathogenic factors and the efficacy of protective mechanisms are critical to disease development. In this study, we characterized an immunoassay that quantified the total capacity of the plasma to degrade or mask OxPLs, thereby preventing their interaction with cells and soluble proteins. OxLDL-coated plates were first incubated with human blood plasma or a control vehicle, followed by an ELISA using a monoclonal antibody specific to oxidized phosphatidylethanolamine. Pretreatment with the diluted blood plasma markedly inhibited mAb binding. The masking assay was optimized by evaluating the buffer composition, the compatibility with various anticoagulants, potential interfering compounds, the kinetic parameters, pre-analytical stability, statistical robustness, and intra- and inter-individual variability. We propose that this masking assay provides a simple immunological approach to assessing protective mechanisms against lipid peroxidation products. Establishing this robust and reproducible method is essential for conducting clinical association studies that explore masking activity as a potential biomarker of the predisposition to a broad range of lipid-peroxidation-related diseases. Full article
(This article belongs to the Special Issue Exploring Biomarkers of Oxidative Stress in Health and Disease)
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14 pages, 722 KiB  
Article
When the Last Line Fails: Characterization of Colistin-Resistant Acinetobacter baumannii Reveals High Virulence and Limited Clonal Dissemination in Greek Hospitals
by Dimitrios Karakalpakidis, Theofilos Papadopoulos, Michalis Paraskeva, Michaela-Eftychia Tsitlakidou, Eleni Vagdatli, Helen Katsifa, Apostolos Beloukas, Charalampos Kotzamanidis and Christine Kottaridi
Pathogens 2025, 14(8), 730; https://doi.org/10.3390/pathogens14080730 - 24 Jul 2025
Abstract
Acinetobacter baumannii has emerged as a major pathogen responsible for healthcare-associated infections, particularly in intensive care units, contributing to significant morbidity and mortality due to its multidrug resistance and ability to persist in clinical environments. This study aimed to investigate the phenotypic and [...] Read more.
Acinetobacter baumannii has emerged as a major pathogen responsible for healthcare-associated infections, particularly in intensive care units, contributing to significant morbidity and mortality due to its multidrug resistance and ability to persist in clinical environments. This study aimed to investigate the phenotypic and genomic characteristics of all multidrug-resistant A. baumannii isolates collected between January and June 2022 from two tertiary care hospitals in Thessaloniki, Greece. A total of 40 isolates were included. All isolates exhibited resistance to colistin; however, none harbored the mcr-1 to mcr-9 genes, as confirmed by polymerase chain reaction (PCR). PCR-based screening for virulence-associated genes revealed high prevalence rates of basD (100%), pld (95%), csuE (87.5%), and bap (77.5%). In contrast, ompA and pglC were not detected. Twitching motility ranged from 2 to 50 mm, with 25% of the isolates classified as non-motile and 20% as highly motile. Swarming motility was observed in all strains. Additionally, all isolates demonstrated positive α-hemolysis, suggesting a potential virulence mechanism involving tissue damage and iron acquisition. Pulsed-field gel electrophoresis (PFGE) revealed significant genomic diversity among the isolates, indicating a low likelihood of patient-to-patient or clonal transmission within the hospital setting. These findings highlight the complex relationship between antimicrobial resistance and virulence in clinical A. baumannii isolates and emphasize the urgent need for robust infection control strategies and continued microbiological surveillance. Full article
(This article belongs to the Special Issue Acinetobacter baumannii: An Emerging Pathogen)
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19 pages, 11764 KiB  
Article
Emerging Highly Pathogenic Avian Influenza H5N1 Clade 2.3.4.4b Causes Neurological Disease and Mortality in Scavenging Ducks in Bangladesh
by Rokshana Parvin, Sumyea Binta Helal, Md Mohi Uddin, Shadia Tasnim, Md. Riabbel Hossain, Rupaida Akter Shila, Jahan Ara Begum, Mohammed Nooruzzaman, Ann Kathrin Ahrens, Timm Harder and Emdadul Haque Chowdhury
Vet. Sci. 2025, 12(8), 689; https://doi.org/10.3390/vetsci12080689 - 23 Jul 2025
Abstract
Scavenging domestic ducks significantly contribute to the transmission and maintenance of highly pathogenic H5N1 clade 2.3.4.4b avian influenza viruses in Bangladesh, a strain of growing global concern due to its broad host range, high pathogenicity, and spillover potential. This study investigates the molecular [...] Read more.
Scavenging domestic ducks significantly contribute to the transmission and maintenance of highly pathogenic H5N1 clade 2.3.4.4b avian influenza viruses in Bangladesh, a strain of growing global concern due to its broad host range, high pathogenicity, and spillover potential. This study investigates the molecular epidemiology and pathology of HPAI H5N1 viruses in unvaccinated scavenging ducks in Bangladesh, with the goal of assessing viral evolution and associated disease outcomes. Between June 2022 and March 2024, 40 scavenging duck flocks were investigated for HPAI outbreaks. Active HPAIV H5N1 infection was detected in 35% (14/40) of the flocks using RT-qPCR. Affected ducks exhibited clinical signs of incoordination, torticollis, and paralysis. Pathological examination revealed prominent meningoencephalitis, encephalopathy and encephalomalacia, along with widespread lesions in the trachea, lungs, liver, and spleen, indicative of systemic HPAIV infection. A phylogenetic analysis of full-genome sequences confirmed the continued circulation of clade 2.3.2.1a genotype G2 in these ducks. Notably, two samples of 2022 and 2023 harbored HPAIV H5N1 of clade 2.3.4.4b, showing genetic similarity to H5N1 strains circulating in Korea and Vietnam. A mutation analysis of the HA protein in clade 2.3.4.4b viruses revealed key substitutions, including T156A (loss of an N-linked glycosylation site), S141P (antigenic site A), and E193R/K (receptor-binding pocket), indicating potential antigenic drift and receptor-binding adaptation compared to clade 2.3.2.1a. The emergence of clade 2.3.4.4b with the first report of neurological and systemic lesions suggests ongoing viral evolution with increased pathogenic potential for ducks. These findings highlight the urgent need for enhanced surveillance and biosecurity to control HPAI spread in Bangladesh. Full article
17 pages, 3346 KiB  
Article
Phytoconstituent Detection, Antioxidant, and Antimicrobial Potentials of Moringa oleifera Lam. Hexane Extract Against Selected WHO ESKAPE Pathogens
by Kokoette Bassey and Malebelo Mabowe
Horticulturae 2025, 11(8), 869; https://doi.org/10.3390/horticulturae11080869 - 23 Jul 2025
Abstract
The holistic use of Moringa oleifera Lam. seeds is not as popular amongst rural South Africans. This study screened for the phytochemicals, antimicrobial, and antioxidant potentials as well identifying the compounds in the oils of South African Moringa seed oils using cost-effective thin [...] Read more.
The holistic use of Moringa oleifera Lam. seeds is not as popular amongst rural South Africans. This study screened for the phytochemicals, antimicrobial, and antioxidant potentials as well identifying the compounds in the oils of South African Moringa seed oils using cost-effective thin layer chromatography bioautography and dot blot assays, because fewer studies have been conducted using seed samples from this country. The results obtained indicated that the best oil extract yield (24.04%) was obtained for hexane from 60.10 g of powdered seeds. The yield of the other extracts ranged from 6.2 to 9.5%. Positive test results were obtained for terpenoids, steroids, alkaloids, flavonoids, phenols, and tannins, with potentially good antioxidant properties for scavenging free radicals from 2,2-diphenyl-1-picrylhydrazyl (DPPH) and good antimicrobial activity against Acinetobacter baumannii (BAA 747), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 27853), and Pseudomonas aeruginosa (ATCC 27853), with the best zone of inhibition of 314.2 mm2 obtained for oil extracted with hexane, followed by dichloromethane, methanol, and acetone oil extracts, respectively. The best minimum inhibitory concentration (MIC) of 0.032 mg/mL against P. aeruginosa was recorded for the hexane oil, compared with ciprofloxacin, which had an MIC of 0.0039 mg/mL against the same pathogen. The identification of the in-oil compounds proposed to mitigate inhibitory activity against the test microbes was carried out through GC-MS analysis matching our results with the GC-MS library. These compounds included ursane-3,16-diol, azetidin-2-one, 1-benzyl-4à-methyl, dibutyl phthalate, 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene, 1H-pyrrole-2,5-dione, 3-ethyl-4-methyl, octopamine rhodoxanthin, 29,30-dinorgammacerane-3,22-diol, 21,21-dimethy, cholan-24-oic acid, 3,7-dioxo, and benzyl alcohol. These are in addition to the stability-indicating marker compounds like oleic acid (54.9%), 9-Octadecenoic acid (z)-, methyl ester (23.3%), n-hexadecanoic acid (9.68%), among others observed over a five year period. Full article
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15 pages, 2688 KiB  
Article
Recombinant Tetrameric Neuraminidase Subunit Vaccine Provides Protection Against Swine Influenza A Virus Infection in Pigs
by Ao Zhang, Bin Tan, Jiahui Wang and Shuqin Zhang
Vaccines 2025, 13(8), 783; https://doi.org/10.3390/vaccines13080783 - 23 Jul 2025
Abstract
Background/Objectives: Swine influenza A virus (swIAV), a prevalent respiratory pathogen in porcine populations, poses substantial economic losses to global livestock industries and represents a potential threat to public health security. Neuraminidase (NA) has been proposed as an important component for universal influenza [...] Read more.
Background/Objectives: Swine influenza A virus (swIAV), a prevalent respiratory pathogen in porcine populations, poses substantial economic losses to global livestock industries and represents a potential threat to public health security. Neuraminidase (NA) has been proposed as an important component for universal influenza vaccine development. NA has potential advantages as a vaccine antigen in providing cross-protection, with specific antibodies that have a broad binding capacity for heterologous viruses. In this study, we evaluated the immunogenicity and protective efficacy of a tetrameric recombinant NA subunit vaccine in a swine model. Methods: We constructed and expressed structurally stable soluble tetrameric recombinant NA (rNA) and prepared subunit vaccines by mixing with ISA 201 VG adjuvant. The protective efficacy of rNA-ISA 201 VG was compared to that of a commercial whole inactivated virus vaccine. Pigs received a prime-boost immunization (14-day interval) followed by homologous viral challenge 14 days post-boost. Results: Both rNA-ISA 201 VG and commercial vaccine stimulated robust humoral responses. Notably, the commercial vaccine group exhibited high viral-binding antibody titers but very weak NA-specific antibodies, whereas rNA-ISA 201 VG immunization elicited high NA-specific antibody titers alongside substantial viral-binding antibodies. Post-challenge, both immunization with rNA-ISA 201 VG and the commercial vaccine were effective in inhibiting viral replication, reducing viral load in porcine respiratory tissues, and effectively mitigating virus-induced histopathological damage, as compared to the PBS negative control. Conclusions: These findings found that the anti-NA immune response generated by rNA-ISA 201 VG vaccination provided protection comparable to that of a commercial inactivated vaccine that primarily induces an anti-HA response. Given that the data are derived from one pig per group, there is a requisite to increase the sample size for more in-depth validation. This work establishes a novel strategy for developing next-generation SIV subunit vaccines leveraging NA as a key immunogen. Full article
(This article belongs to the Special Issue Vaccine Development for Swine Viral Pathogens)
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26 pages, 8725 KiB  
Article
Novel 3D-Printed Replica Plate Device Ensures High-Throughput Antibacterial Screening of Halophilic Bacteria
by Kaloyan Berberov, Nikolina Atanasova, Nikolay Krumov, Boryana Yakimova, Irina Lazarkevich, Stephan Engibarov, Tsvetozara Damyanova, Ivanka Boyadzhieva and Lyudmila Kabaivanova
Mar. Drugs 2025, 23(8), 295; https://doi.org/10.3390/md23080295 - 23 Jul 2025
Abstract
Antibiotic resistance is one of the most significant public health issues today. As a consequence, there is an urgent need for novel classes of antibiotics. This necessitates the development of highly efficient screening methods for the rapid identification of antibiotic-producing bacteria. Here, we [...] Read more.
Antibiotic resistance is one of the most significant public health issues today. As a consequence, there is an urgent need for novel classes of antibiotics. This necessitates the development of highly efficient screening methods for the rapid identification of antibiotic-producing bacteria. Here, we describe a new method for high-throughput screening of antimicrobial compounds (AMC) producing halophilic bacteria. Our methodology used a newly designed 3D-printed Petri plate replicator used for drop deposition and colony replication. We employed this device in combination with a modified agar overlay assay to screen more than 7400 bacterial colonies. A total of 54 potential AMC producers were discovered at a success rate of 0.7%. Although 40% of them lost their antibacterial activity during the secondary screening, 22 strains retained inhibitory activity and were able to suppress the growth of one or more safe relatives of the ESKAPE group pathogens. The ethyl acetate extract from the most potent strain, Virgibacillus salarius POTR191, demonstrated moderate antibacterial activity against Enterococcus faecalis, Acinetobacter baumanii, and Staphylococcus epidermidis with minimal inhibitory concentrations of 128 μg/mL, 128 μg/mL, and 512 μg/mL, respectively. We propose that our replica plate assay could be used for target-based antimicrobial screening of various extremophilic bacteria. Full article
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13 pages, 2088 KiB  
Article
Assessment of Effects of Storage Time on Fermentation Profile, Chemical Composition, Bacterial Community Structure, Co-Occurrence Network, and Pathogenic Risk in Corn Stover Silage
by Zhumei Du, Ying Meng, Yifan Chen, Shaojuan Cui, Siran Wang and Xuebing Yan
Fermentation 2025, 11(8), 425; https://doi.org/10.3390/fermentation11080425 - 23 Jul 2025
Abstract
In order to achieve the efficient utilization of agricultural by-products and overcome the bottleneck of animal feed shortages in dry seasons, this study utilized corn stover (CS; Zea mays L.) as a material to systematically investigate the dynamic changes in the fermentation quality, [...] Read more.
In order to achieve the efficient utilization of agricultural by-products and overcome the bottleneck of animal feed shortages in dry seasons, this study utilized corn stover (CS; Zea mays L.) as a material to systematically investigate the dynamic changes in the fermentation quality, bacterial community structure, and pathogenic risk of silage under different fermentation times (0, 3, 7, 15, and 30 days). CS has high nutritive value, including crude protein and sugar, and can serve as a carbon source and a nitrogen source for silage fermentation. After ensiling, CS silage (CSTS) exhibited excellent fermentation quality, characterized by relatively high lactic acid content, low pH, and ammonia nitrogen content within an acceptable range. In addition, neither propionic acid nor butyric acid was detected in any of the silages. CS exhibited high α-diversity, with Serratia marcescens being the dominant bacterial species. After ensiling, the α-diversity significantly (p < 0.05) decreased, and Lactiplantibacillus plantarum was the dominant species during the fermentation process. With the extension of fermentation days, the relative abundance of Lactiplantibacillus plantarum significantly (p < 0.05) increased, reaching a peak and stabilizing between 15 and 30 days. Ultimately, lactic acid bacteria dominated and constructed a microbial symbiotic network system. In the bacterial community of CSTS, the abundance of “potential pathogens” was significantly (p < 0.01) lower than that of CS. These results provide data support for establishing a microbial regulation theory for silage fermentation, thereby improving the basic research system for the biological conversion of agricultural by-products and alleviating feed shortages in dry seasons. Full article
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26 pages, 1443 KiB  
Review
Bacteriophages as Agents for Plant Disease Control: Where Are We After a Century?
by Manoj Choudhary, Ibukunoluwa A. Bankole, Sophia T. McDuffee, Apekshya Parajuli, Mousami Poudel, Botond Balogh, Mathews L. Paret and Jeffrey B. Jones
Viruses 2025, 17(8), 1033; https://doi.org/10.3390/v17081033 - 23 Jul 2025
Abstract
The rise in antibiotic-resistant bacteria has made the management of bacterial diseases increasingly challenging. As a result, bacteriophages have gained attention as a promising alternative to antibiotics for combating bacterial pathogens. However, the usage of phages as biocontrol agents faces many challenges, including [...] Read more.
The rise in antibiotic-resistant bacteria has made the management of bacterial diseases increasingly challenging. As a result, bacteriophages have gained attention as a promising alternative to antibiotics for combating bacterial pathogens. However, the usage of phages as biocontrol agents faces many challenges, including environmental stability, delivery efficiency, host specificity, and potential bacterial resistance. Advancements in genetic engineering and nanotechnology have been explored to enhance the stability, efficacy, and adaptability of phage-based treatments. In this review, we discuss the key barriers to the effective implementation of phage therapy and highlight innovative strategies to overcome these challenges. By addressing these limitations, this review aims to provide insights into optimizing phage-based approaches for widespread therapeutic and biocontrol applications. Full article
(This article belongs to the Special Issue Bacteriophage-Based Biocontrol in Agriculture, 2nd Edition)
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11 pages, 1677 KiB  
Article
Exposure to Treponema pallidum Alters Villous Histomorphology of Human Placentae
by Patience B. Tetteh-Quarcoo, Joana Twasam, John Ahenkorah, Bismarck Afedo Hottor, Nicholas T. K. D. Dayie, Stephen Opoku-Nyarko, Peter Ofori Appiah, Emmanuel Afutu, Fleischer C. N. Kotey, Eric S. Donkor, Emilia Asuquo Udofia, Nii Koney-Kwaku Koney, Benjamin Arko-Boham and Kevin Kofi Adutwum-Ofosu
Acta Microbiol. Hell. 2025, 70(3), 31; https://doi.org/10.3390/amh70030031 - 23 Jul 2025
Abstract
Syphilis, which is caused by Treponema pallidum, remains one of the most common congenital infection worldwide and has tremendous consequences for the mother and her developing foetus if left untreated. The complexity of the exposure to this pathogen extends beyond the well-established [...] Read more.
Syphilis, which is caused by Treponema pallidum, remains one of the most common congenital infection worldwide and has tremendous consequences for the mother and her developing foetus if left untreated. The complexity of the exposure to this pathogen extends beyond the well-established clinical manifestations, as it can profoundly affect placental histomorphology. This study aimed to compare T. pallidum-exposed placental villi structures with healthy placentae at term to evaluate the histomorphological differences using stereology. In this case-control study conducted at term (38 weeks ± 2 weeks), 78 placentae were collected from the hospital delivery suites, comprising 39 cases (T. pallidum-exposed) and 39 controls (non-exposed), who were gestational age-matched with other potential confounders excluded. Blood samples from the umbilical vein and placental basal plate were tested for syphilis, using rapid diagnostic test (RDT) kits for T. pallidum (TP) antibodies (IgG and IgM) to classify placentae as exposed to T. pallidum (cases) and non-exposed (controls). Tissue sections were prepared and stained with haematoxylin and eosin, and the mean volume densities of syncytial knots, foetal capillaries, syncytial denuded areas, and intervillous spaces were estimated using stereological methods. Statistical analysis was performed to compare the mean values between the case and control groups. Stereological assessment revealed significant differences between the T. pallidum-exposed and non-exposed groups with regard to syncytial knots (p < 0.0001), syncytial denudation (p < 0.0001), and foetal capillaries (p < 0.0001), but no significant difference in the intervillous space was found (p = 0.1592). Therefore, our study shows, for the first time, that the histomorphology of human placental villi appears to be altered by exposure to T. pallidum. It will, therefore, be interesting to determine whether these changes in the placental villi translate into long-term effects on the baby. Full article
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27 pages, 1201 KiB  
Review
Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients
by Aitor Gonzaga, Gema Martinez-Navarrete, Loreto Macia, Marga Anton-Bonete, Gladys Cahuana, Juan R. Tejedo, Vanessa Zorrilla-Muñoz, Eduardo Fernandez-Jover, Etelvina Andreu, Cristina Eguizabal, Antonio Pérez-Martínez, Carlos Solano, Luis Manuel Hernández-Blasco and Bernat Soria
Biomedicines 2025, 13(8), 1801; https://doi.org/10.3390/biomedicines13081801 - 23 Jul 2025
Abstract
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). [...] Read more.
Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article
(This article belongs to the Section Gene and Cell Therapy)
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19 pages, 9109 KiB  
Article
Metformin Enhances Doxycycline Efficacy Against Pasteurella multocida: Evidence from In Vitro, In Vivo, and Morphological Studies
by Nansong Jiang, Weiwei Wang, Qizhang Liang, Qiuling Fu, Rongchang Liu, Guanghua Fu, Chunhe Wan, Longfei Cheng, Yu Huang and Hongmei Chen
Microorganisms 2025, 13(8), 1724; https://doi.org/10.3390/microorganisms13081724 - 23 Jul 2025
Abstract
Pasteurella multocida (Pm) is a zoonotic pathogen that poses a significant threat to animal health and causes substantial economic losses, further aggravated by rising tetracycline resistance. To restore the efficacy of tetracyclines to Pm, we evaluated the synergistic antibacterial activity [...] Read more.
Pasteurella multocida (Pm) is a zoonotic pathogen that poses a significant threat to animal health and causes substantial economic losses, further aggravated by rising tetracycline resistance. To restore the efficacy of tetracyclines to Pm, we evaluated the synergistic antibacterial activity of doxycycline combined with metformin, an FDA-approved antidiabetic agent. Among several non-antibiotic adjuvant candidates, metformin exhibited the most potent in vitro synergy with doxycycline, especially against capsular serogroup A strain (PmA). The combination demonstrated minimal cytotoxicity and hemolysis in both mammalian and avian cells and effectively inhibited resistance development under doxycycline pressure. At 50 mg/kg each, the combination of metformin and doxycycline significantly reduced mortality in mice and ducks acutely infected with PmA (from 100% to 60%), decreased pulmonary bacterial burdens, and alleviated tissue inflammation and damage. Mechanistic validation confirmed that metformin enhances membrane permeability in Pm without compromising membrane integrity, dissipates membrane potential, increases intracellular doxycycline accumulation, and downregulates the transcription of the tetracycline efflux gene tet(B). Morphological analyses further revealed pronounced membrane deformation and possible leakage of intracellular contents. These findings highlight metformin as a potent, low-toxicity tetracycline adjuvant with cross-species efficacy, offering a promising therapeutic approach for managing tetracycline-resistant Pm infections. Full article
(This article belongs to the Section Veterinary Microbiology)
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28 pages, 1763 KiB  
Review
Interaction Between Konjac Glucomannan and Gut Microbiota and Its Impact on Health
by Yufen Yu, Shuo Jin, Yi Yang, Xiaodong Han, Rongfa Guan and Hao Zhong
Biology 2025, 14(8), 923; https://doi.org/10.3390/biology14080923 - 23 Jul 2025
Abstract
Konjac glucomannan (KGM) is a natural polysaccharide polymer. It is degraded by gut microbiota-derived β-mannanase into small-molecule nutrients, which exert diverse physiological regulatory effects. As a prebiotic, KGM modulates gut microbiota composition. It selectively fosters the proliferation of beneficial commensals and suppresses potential [...] Read more.
Konjac glucomannan (KGM) is a natural polysaccharide polymer. It is degraded by gut microbiota-derived β-mannanase into small-molecule nutrients, which exert diverse physiological regulatory effects. As a prebiotic, KGM modulates gut microbiota composition. It selectively fosters the proliferation of beneficial commensals and suppresses potential pathogens, thereby alleviating microbiota-related disorders. Moreover, microbiota fermentation of KGM produces metabolites. Short-chain fatty acids (SCFAs) are particularly notable among these metabolites. They exert multifaceted beneficial effects, including metabolic regulation, intestinal barrier strengthening, and neuroprotective functions. These effects are mediated through inhibition of inflammatory pathways (e.g., NF-κB, MAPK), modulation of lipid metabolism genes (e.g., CD36), and regulation of neurotransmitters (e.g., GABA, 5-HT). This highlights KGM’s therapeutic potential for metabolic, inflammatory, and neurodegenerative diseases. Current clinical use is limited by dose-dependent adverse effects and interindividual response variability, which stem from different microbial communities. This necessitates personalized dosage strategies. Despite these limitations, KGM as a prebiotic polysaccharide exhibits multifaceted bioactivity. Current evidence suggests its potential to synergistically modulate metabolic pathways, gut microbiota composition, immune cell signaling, and neuroendocrine interactions. This highlights its promise for developing novel therapeutic interventions. Full article
(This article belongs to the Special Issue Gut Microbiome in Health and Disease (2nd Edition))
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16 pages, 6389 KiB  
Article
Biocontrol Potential of Rhizosphere Bacteria Against Fusarium Root Rot in Cowpea: Suppression of Mycelial Growth and Conidial Germination
by Qinghua Zhu, Yixuan Ma, Tong Zhang, Weirong Liu, Songbai Zhang, Yue Chen, Di Peng and Xin Zhang
Biology 2025, 14(8), 921; https://doi.org/10.3390/biology14080921 - 23 Jul 2025
Abstract
The cultivation of cowpea (Vigna unguiculata), a vital vegetable crop, faces significant threats from Fusarium spp.-induced root rot. In this study, three fungal pathogens (Fusarium falciforme HKFf, Fusarium incarnatum HKFi, and Fusarium oxysporum HKFo) were isolated from symptomatic cowpea plants, [...] Read more.
The cultivation of cowpea (Vigna unguiculata), a vital vegetable crop, faces significant threats from Fusarium spp.-induced root rot. In this study, three fungal pathogens (Fusarium falciforme HKFf, Fusarium incarnatum HKFi, and Fusarium oxysporum HKFo) were isolated from symptomatic cowpea plants, and we screened 90 rhizobacteria from healthy rhizospheres using six culture media. Among these pathogens, Priestia megaterium TSA-10E showed a notable suppression of F. oxysporum HKFo (63.21%), F. incarnatum HKFi (55.16%), and F. falciforme HKFf (50.93%). In addition, Bacillus cereus KB-6 inhibited the mycelial growth of F. incarnatum HKFi and F. oxysporum HKFo by 42.39% and 47.93%, respectively. Critically, cell-free filtrates from P. megaterium TSA-10E and B. cereus KB-6 cultures reduced conidial germination in F. oxysporum HKFo and F. incarnatum HKFi, highlighting their role in disrupting the early infection stages. In greenhouse trials, TSA-10E and KB-6 reduced disease severity by 48.7% and 40.4%, respectively, with treated plants maintaining healthy growth while untreated controls succumbed to wilting. Broad-spectrum assays revealed that B. subtilis TSA-6E and P. megaterium TSA-10E were potent antagonists against both economic and grain crop pathogens. These findings underscore the potential of rhizobacteria as sustainable biocontrol agents for managing root rot disease caused by Fusarium spp. in cowpea cultivation. Full article
(This article belongs to the Special Issue Advances in Research on Diseases of Plants (2nd Edition))
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