Search Results (1,791)

This review examines strategies to enhance the antifungal properties of commercial soft lining materials (SLMs) through modification with plant-derived oils, extracts, and powders. These natural bioactive compounds act via multiple mechanisms, including disruption of fungal cell membranes, inhibition of biofilm formation, and interference with Candida albicans metabolism, the pathogen causing denture-associated candidiasis. Their incorporation into SLM provides localized antifungal activity at the denture–mucosa interface. The review highlights Aloe vera (aloe), Azadirachta indica (neem), Ocimum basilicum (basil), Melaleuca alternifolia (tea tree), Cocos nucifera (coconut), Allium sativum (garlic), Thymus vulgaris (thyme), and chitosan as notable sources of phytotherapeutics that consistently inhibit C. albicans growth. In addition to antimicrobial effects, studies assessed both intrinsic (hardness, tensile strength, tear strength) and interfacial (bond strength) mechanical properties, as well as surface roughness. Most formulations maintained acceptable mechanical performance and improved surface smoothness. Key limitations include rapid leaching of active compounds, variability in testing methods, and insufficient in vivo and cytotoxicity data. Future research should prioritize the high-quality purification of natural extracts, the isolation of well-defined bioactive compounds, and the design of systems enabling selective and sustained release of these agents, ensuring reproducibility, enhanced stability, and clinical reliability of next-generation bioactive SLMs. Full article

The intestinal microflora, which is vital for nutrient absorption and immune regulation, can experience dysbiosis under environmental stress, potentially enhancing host susceptibility to pathogenic invasion. The impact of ocean acidification on bivalves is substantial, but its effects on their intestinal microflora remain poorly understood. To explore the impact of ocean acidification on the intestinal microflora of Sinonovacula constricta, this study used high-throughput 16S rRNA sequencing technology to investigate the variations in the intestinal microflora communities of S. constricta during ocean acidification across different time points. After exposure to ocean acidification, changes in the composition of the intestinal microflora of S. constricta were observed, with no significant difference in α-diversity between the acidified and control groups. The abundance of Proteobacteria in the acidification group increased, whereas that of Cyanobacteria decreased. The abundance of Firmicutes initially decreased and then increased. At the genus level, the relative abundance of Pseudomonas was lower than that in the control group, whereas the relative abundance of Photobacterium, Acinetobacter, and Enterobacter gradually increased. LEfSe analysis identified Serpens as the discriminative biomarker at 7 days of acidification, Enterobacteriales, Rhodobacteraceae, and Martvita at 14 days of acidification, and Serpens, Acidibacteria, and Aeromonadaceae at 35 days of acidification. Functional prediction analysis indicated significant stimulation in various metabolic pathways at different time points following acidification stress. Specifically, pathways involved in biosynthesis were significantly stimulated at 14 days of acidification, while those related to sucrose degradation were disrupted at 35 days. The results further indicated that ocean acidification stress can influence the intestinal microflora of S. constricta, but no severe dysbiosis or digestive system impairment was observed at the microbial level. This study provides new insights into the effects of ocean acidification on the intestinal microflora of marine bivalves. Full article

Dengue virus (DENV) is a major global health concern, with pathogenesis driven by complex interactions between the virus, host genetics, and immune responses. Key determinants of disease severity include antibody-dependent enhancement (ADE), cross-reactive T cells, anti-NS1 antibodies, autoimmunity, and genetic predisposition, with the NS1 protein and its antibodies strongly implicated in severe dengue. This review highlights recent advances in our understanding of how DENV impacts host immune responses at cellular, molecular, and genetic levels. We particularly focus on how the virus interacts with the host, alters immune responses, and escapes immune detection. These factors are crucial for disease progression and immune dysfunction. The host mounts both innate and adaptive immune responses involving interferon signalling, cytokine production, antigen presentation, and T-cell activation. However, DENV evades immunity by suppressing interferon pathways, disrupting antigen presentation, and leveraging antibody-dependent enhancement (ADE), leading to immune dysregulation, prolonged viremia, and severe dengue. Gaining insight into these host-pathogen interactions is essential for understanding dengue pathogenesis for designing safer and more effective therapeutics. Furthermore, integrating omics approaches with immune response models shows promise for identifying early, reliable markers that can predict disease severity and guide treatment. A deeper understanding of these processes will support the development of personalised treatment strategies and enhance preparedness for future dengue outbreaks. Full article

Background: Commercial oral care products commonly incorporate synthetic antimicrobials such as cetylpyridinium chloride (Cetyl Cl.), L-Arginine (L-arg.), and stannous fluoride (SnF₂). Although effective against oral pathogens, these agents are often associated with adverse effects including mucosal irritation, taste alteration, and disruption of the oral microbiome. These limitations have spurred growing interest in safer, plant-based alternatives. In this study, we present a two-pronged in vitro oral care testing model that integrates cell assays with machine-guided quantitative microscopy analyses to assess both antibacterial efficacy and host biocompatibility of botanical extracts. Methods: Using Miswak (Salvadora persica) and Neem (Azadirachta indica) as representative natural products, we conducted antibacterial and antibiofilm testing including the evaluation of the minimum inhibitory concentration (MIC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC), alongside biocompatibility assessments via MTT cell viability assays on probiotic bacteria and mammalian oral cells. To evaluate biofilm structure and disruption, we employed scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), augmented with machine-guided Weka segmentation and automated image analysis. Results: Our findings show that Miswak and Neem extracts exhibited 75–100% antibacterial and antibiofilm efficacy against all tested bacteria, as demonstrated by cell assays and microscopy analyses, comparable to synthetic oral care agents. They also maintained ~100% viability toward commensal microbes and mammalian oral cells, whereas Cetyl Cl. and SnF₂ showed dose-dependent cytotoxicity. Conclusions: This dual-assessment oral care testing model provides a comprehensive and biologically relevant framework for the discovery and screening of safe and effective natural herbal extracts in oral care applications. Full article

Cornelia de Lange Syndrome (CdLS) is a rare multisystem developmental disorder caused primarily by mutations in cohesin complex genes, including RAD21. Psoriasis is a chronic inflammatory skin disease linked to immune dysregulation, notably involving TNFAIP3 (A20), a negative regulator of NF-κB signaling. Although case reports have suggested a possible coexistence of CdLS and psoriasis, the underlying molecular basis has remained unexplored. Here we report the first case of molecular co-occurrence of CdLS and generalized pustular psoriasis in a patient with novel heterozygous nonsense variant in RAD21 (c.1306C>T, p.Gln436*), pathogenic for CdLS type 4, and a previously unreported truncating variant in TNFAIP3 (c.2199C>A, p.Cys733*), predicted to disrupt NF-κB regulation and classified as a variant of uncertain significance. Structural protein modeling showed significant conformational disruption in RAD21 and partial truncation of the ZnF domains of TNFAIP3, supporting their functional impact. This study is the first to suggest a possible molecular mechanism that may explain the rare co-occurrence of CdLS and psoriasis: RAD21 deficiency disrupts chromatin architecture and immune gene regulation, while TNFAIP3 loss-of-function removes critical NF-κB inhibition, resulting in synergistic developmental and inflammatory phenotypes. Secondary transcriptomic data analysis further suggests that RAD21 knockdown may downregulate TNFAIP3 expression, providing a possible mechanistic intersection. Our findings provide the first molecular evidence linking RAD21 and TNFAIP3, introducing a novel pathogenic hypothesis connecting cohesin dysfunction and immune dysregulation. This work expands the mutational spectrum of both genes and opens a new avenue for understanding developmental-inflammatory disease overlap. Full article

Streptococcus pneumoniae is a major opportunistic pathogen and a leading cause of severe infections in infants under two years of age. Human milk oligosaccharides (HMOs), key bioactive components of breast milk, possess immunomodulatory and antimicrobial properties. In this study, the antipneumococcal effects of HMOs are investigated across multiple S. pneumoniae serotypes, focusing on concentration-dependent activity and underlying mechanisms. Growth inhibition and bacterial viability were evaluated using growth curve analysis and colony-forming unit (CFU) assays. HMOs inhibited pneumococcal growth in a concentration-dependent manner, with suppression observed at 1.5–2.5 mg/mL and complete killing at 5 mg/mL for all serotypes. Nonencapsulated strains were more sensitive, with inhibition at 1 mg/mL. In the CFU assays, killing occurred at 1.25–5 mg/mL depending on the strain. At physiologically relevant colostrum concentrations (20–25 mg/mL), HMOs achieved complete bactericidal effects across all the tested strains. In contrast, lactose at equivalent doses showed no measurable antimicrobial activity, confirming the specificity of the observed effects. Overall, HMOs exhibit serotype-independent antipneumococcal activity, possibly through interference with bacterial adhesion or metabolic disruption. These findings suggest a potential role for HMOs as adjunctive agents in the prevention of pneumococcal infections in vulnerable populations, such as infants, and warrant further in vivo studies to validate these effects and explore clinical applications. Full article

Plant fungal diseases pose a serious threat to crop production and safety, and natural products are one of the important directions for the development of new green fungicides. This study found that the extract of Murraya euchristifolia had significant antifungal activity, and a main antifungal coumarin (1) was isolated by bioassay-guided fractionation. The structure of 1 was identified by NMR and MS spectroscopic data as a fused bis-furan coumarin (microminutinin) which was first isolated from the Murraya genus and exhibited strong broad-spectrum antifungal activity against eight plant pathogenic fungi from different families and genera. The EC₅₀ value of 1 (11.33 μg/mL) against Pestalotiopsis theae (the most sensitive to 1) was slightly higher than that (7.03 μg/mL) of the positive drug (80% carbendazim WP), indicating that 1 has the potential to serve as a lead compound for botanical fungicides. The bioassay results against P. theae in vivo indicated that 1 also has the potential for field application. Scanning electron microscopy and optical microscopy revealed that 1 disrupted the morphological structure of mycelium, causing hyphae to twist, shrink, and even crack and severely reducing hyphal branching. Furthermore, propidium iodide staining proved that microminutinin destroyed the integrity of the cell membrane, causing leakage of cellular components. In addition, calcofluor white staining and chitin content changes illustrated that microminutinin disrupted the cell wall structure. This research provides compound sources and a theoretical basis for the development of botanical fungicides. Full article

Background/Objectives: The rise in multidrug-resistant pathogens such as Pseudomonas aeruginosa (PA), coupled with declining antibiotic development, underscores the need for innovative therapeutic strategies. Repurposing approved drugs provides advantages of safety and rapid development. Since quorum sensing (QS) controls key virulence traits in PA, targeting this pathway represents a promising antivirulence approach. This study aimed to identify and repurpose existing drugs as QS inhibitors. Methods: An in silico docking screen of 3000 FDA-approved or clinically tested compounds was performed against the C4-HSL receptor RhlR. Seventeen candidates were tested in the laboratory strain PAO1 for lactone-dependent signaling inhibition. The most active compound, MK-8245, was further evaluated for effects on growth, cytotoxicity, lactone release, biofilm formation, pyocyanin, elastase, rhamnolipids, and swarming motility. Its activity was also assessed in 20 clinical PA isolates. Results: MK-8245 (40 µM) reduced QS-regulated gene expression by ~60% without affecting viability. In PAO1, it inhibited rhamnolipids (60%), pyocyanin (40%), elastase (25%), biofilm formation, and swarming motility (25%). MK-8245 also enhanced the efficacy of imipenem against biofilms. In clinical isolates, it consistently decreased lactone release (~60%), pyocyanin (~50%), rhamnolipids (~40%), biofilm formation (~30%), and swarming motility (~25%). Conclusions: MK-8245 emerges as a promising antivirulence candidate against P. aeruginosa. By disrupting QS signaling and impairing multiple virulence factors, it attenuates pathogenicity without bactericidal pressure. Its synergy with standard antibiotics and consistent activity in clinical isolates highlight its translational potential and warrant further preclinical evaluation. Full article

Plant pathogenic fungi pose a persistent global threat to food security, causing severe yield losses in staple crops and increasing dependence on chemical fungicides. However, the ecological and toxicological drawbacks of synthetic fungicides have intensified the search for safer, plant-derived alternatives. This review synthesizes current advances on the antifungal mechanisms of plant essential oils (EOs) and their prospects for biofungicide development. The literature reveals that the antifungal activity of EOs arises from their diverse phytochemical composition, principally terpenes, phenolics, and aldehydes that target multiple fungal cellular sites. These compounds disrupt membrane integrity through ergosterol depletion, inhibit chitin and β-glucan synthesis, interfere with mitochondrial energy metabolism, and induce oxidative stress, leading to lipid peroxidation and cell death. Morphological and transcriptomic evidence confirms that EOs alter hyphal growth, spore germination, and key gene expression pathways associated with fungal virulence. Furthermore, emerging nanotechnological and encapsulation strategies enhance EO stability, bioavailability, and field persistence, addressing major barriers to their large-scale agricultural application. The integration of EO-based biofungicides within sustainable and precision agriculture frameworks offers a promising route to reduce chemical inputs, mitigate resistance development, and promote ecological balance. This review underscores the need for interdisciplinary research linking phytochemistry, nanotechnology, and agronomy to translate EO-based antifungal mechanisms into next-generation, environmentally compatible crop protection systems. Full article

Background: Limosilactobacillus reuteri (L. reuteri), present in the oral and intestinal microbiota, can colonize the oral cavity through breastfeeding and dairy intake, promoting oral health by balancing the microbiota, inhibiting pathogens, and modulating immune responses. This study aimed to evaluate the preventive role and therapeutic potential of L. reuteri in pediatric oral health. Methods: A literature review was conducted using PubMed, Wiley Library, and the Cochrane Library, supplemented by manual screening, according to PRISMA guidelines and covering the period from January 2011 to 31 December 2024. Results: From 835 records identified, 12 studies met the inclusion criteria. Data shows that L. reuteri strains produce antimicrobial substances that disrupt biofilms and inhibit Streptococcus mutans and other lactobacilli, leading to increased oral pH and improved periodontal indices. The effectiveness of probiotics was found to be strain-specific and transient, with continuous intake and adequate oral hygiene enhancing their ability to colonize the oral cavity. Conclusions: Probiotics show significant potential as therapeutic interventions for controlling cariogenic bacteria and supporting gum health in children. Through mechanisms including bacterial co-aggregation, competitive exclusion, antimicrobial compound synthesis, and immune modulation, probiotics may effectively reduce the risk of tooth decay and gum disease. Their effectiveness depends on the strain, regular intake, proper dosing, good oral hygiene, and suitable delivery, which enhance oral colonization and clinical benefits. Full article

Soil-borne plant pathogens pose a serious threat to global food security by causing extensive yield losses and compromising crop quality. Conventional chemical-based control methods often prove inadequate, environmentally harmful, and disruptive to beneficial soil microbiota, highlighting the urgent need for sustainable alternatives. Plant growth-promoting fungi (PGPF) have emerged as effective biocontrol agents capable of suppressing diverse soil-borne pathogens while simultaneously enhancing plant growth and resilience. This review synthesizes current knowledge on the tripartite interactions among plants, pathogens, and PGPF within the rhizosphere, with emphasis on their roles in disease suppression, rhizosphere competence, and plant health promotion. The findings highlight that PGPF such as Trichoderma, Penicillium, Aspergillus, non-pathogenic Fusarium, hypovirulent binucleate Rhizoctonia and sterile fungi can significantly reduce diseases caused by fungi, oomycetes, bacteria, nematodes, and protists through mechanisms including antibiosis, hyperparasitism, competition, and induction of systemic resistance. Evidence also indicates that consortium approaches and bioformulations enhance field efficacy compared to single-strain applications. Despite this progress, challenges such as variability in field performance, limited shelf life of inoculants, and gaps in understanding ecological interactions constrain large-scale use. Overall, the review underscores that PGPF-based strategies represent a promising and sustainable alternative to chemical pesticides, with strong potential for integration into holistic crop disease management under changing climatic conditions. Full article

Bivalve molluscs represent an important food source and have a significant economic impact through their commercialization in many countries. As high-capacity filter feeders, they can bioaccumulate contaminants and pathogens, creating tangible consumer health risks. This study presents the first comprehensive patent landscape of bivalve mollusc decontamination technologies indexed in international patent databases (Espacenet). The survey identified 30 patents filed between 1989 and 2025. Unlike reviews based solely on scientific literature, this work provides, for the first time, a global mapping of technological developments aimed at enhancing the safety of bivalves-derived foods. The analysis highlights depuration as the predominant technology, which continues to be refined and optimized. It also reveals the emergence of disruptive approaches—such as photodynamic sterilization, the use of probiotics, immunopotentiators, natural antimicrobial compounds, and genetic hybridization—developed to preserve the viability and sensory quality of the organisms. The novelty of this study lies in providing a technological overview of innovation within the aquaculture sector, emphasizing the transition from conventional methods to cleaner, integrated, and sustainable technologies. Furthermore, the research identifies the advancement of hybrid decontamination systems that combine microbiological efficiency, environmental preservation, and commercial value, contributing to safer and more technologically advanced shellfish production. Full article

The SLC26A4 gene is one of the key genes involved in the etiology of hearing loss. It encodes pendrin, a transmembrane transporter protein functioning as a multifunctional anion exchanger. About 600 pathogenic SLC26A4 variants are known to cause either nonsyndromic recessive hearing loss (DFNB4) or Pendred syndrome (hearing loss and thyroid dysfunction). While most pathogenic variants occur in coding regions and disrupt pendrin structure or function, about 25% are thought to impair splicing. For many, pathogenicity has been assessed only in silico, with limited experimental confirmation. We identified several novel and rare SLC26A4 variants in patients with hearing loss from the Tyva and Altai Republics (Southern Siberia, Russia). Based on splicing predictions, six variants—intronic c.2034+1G>A, c.1545-168A>G, c.1708-125T>C, c.1708-18T>A, c.1804-31C>T, and exonic c.942A>G—were selected for analysis using a minigene assay. The results of in vitro analysis only partially matched in silico predictions: c.2034+1G>A caused aberrant splicing; c.1708-18T>A led to exon 16 skipping only in a small proportion of transcripts; the remaining variants showed no detectable splicing effect. These findings underscore the need for integrating in silico predictions with in vitro validation to accurately assess the functional impact of genetic variants, enabling their correct interpretation and reliable molecular diagnosis. Full article

The oral cavity harbors one of the most diverse microbial ecosystems in the human body, second only to the gut. Periodontitis, a chronic inflammatory disease arising from oral microbiota dysbiosis, has been increasingly associated with systemic disorders such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and neurodegenerative conditions. Although hematogenous dissemination of oral pathogens and inflammatory mediators has long been proposed as a mechanistic link, emerging evidence identifies the oral–gut axis as a novel bidirectional pathway. Swallowed oral pathobionts, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can colonize the gut, disrupt the intestinal barrier, and induce dysbiosis, immune imbalance, and metabolic alterations that aggravate systemic inflammation and disease progression. In contrast, gut dysbiosis, especially in obesity or high-fat-diet models, can exacerbate periodontal tissue destruction through hyperuricemia, altered bone metabolism, and Th17/Treg immune imbalance. Experimental and clinical studies further support this reciprocal relationship, implicating microbial, metabolic, and immune crosstalk in both oral and systemic pathology. Understanding this oral–gut–systemic axis offers a paradigm shift in diagnostics and therapeutics, focusing on precision interventions such as microbiome modulation, probiotics, and integrated oral care to mitigate systemic inflammatory burden and improve overall health outcomes. Full article

Viral zoonoses or viral pathogens transmitted from animals to humans—constitute a rapidly intensifying global health and economic challenge. They are responsible for an estimated 2.5 billion illnesses and 2.7 million deaths annually, representing nearly 60% of all infectious diseases and 75% of newly emerging infections. Recent outbreaks, including Coronavirus disease 2019 (COVID-19), Ebola, Nipah, and avian influenza, underscore their capacity to overwhelm health systems, with COVID-19 alone projected to reduce global Gross Domestic Product by USD 22 trillion by 2025 and impose annual healthcare costs of USD 2–3 trillion. Beyond mortality and morbidity, zoonotic events disrupt trade, depress rural livelihoods, and inflict agricultural losses exceeding USD 100 billion per outbreak, with impacts disproportionately borne by low- and middle-income countries. Hotspot regions across tropical North and South America, Asia, and Central Africa remain especially vulnerable due to accelerating land use change, climate variability, and intensified wildlife–human interfaces. While the Global One Health Index highlights high regional heterogeneity, with sub-Saharan Africa scoring lowest, a critical gap persists between the conceptual strength of One Health and its operationalization in resource-limited settings. This review synthesizes evidence on drivers, clinical manifestations, and socioeconomic burdens of viral zoonoses, while highlighting novel perspectives on equity gaps, co-infection dynamics, and limitations of global preparedness initiatives. We argue that current strategies remain over-reliant on donor-driven agendas and insufficiently integrated across sectors. Addressing future zoonotic threats requires prioritizing surveillance in high-risk geographies, integrating epidemiological and economic data for preparedness planning, and supporting context sensitive One Health approaches that confront political, financial, and structural barriers to implementation. Full article