bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–07–19
fifty-two papers selected by
Luca Bolliger, lxBio



  1. Front Immunol. 2026 ;17 1856088
      The host immune system typically recognizes administered bacteriophages as foreign entities, potentially acting as a rate-limiting factor in phage therapy via neutralizing antibody production and immune-mediated clearance. Furthermore, the emergence of bacterial phage resistance during treatment remains a major hurdle for its clinical application. Although employing phage cocktails is the standard strategy to suppress phage resistance, clinical trials occasionally report the emergence of phage-resistant variants despite cocktail treatments. Therefore, a more proactive strategic approach that goes beyond merely preventing resistance and instead actively steers the trajectory of bacterial evolution must be applied. In this context, immuno-phage synergy, in which phages and host immunity act in an orchestrated manner rather than in competition, has recently gained significant traction. To evade phage infection, pathogenic bacteria often mutate or shed crucial surface structures (e.g., capsules, lipopolysaccharides, and pili), thereby incurring fitness costs as evolutionary trade-offs. This mini-review summarizes recent insights into how these trade-offs drastically enhance host immune clearance, including increased susceptibility to neutrophil-mediated opsonophagocytosis, complement-dependent killing, and host chemical barriers. By understanding and exploiting the dynamics of phage-induced selective pressure and immunological trade-offs, the evolutionary arms race could be altered to intentionally drive pathogens into evolutionary traps. Concurrently, we discuss emerging clinical challenges, such as unexpected immune evasion (trade-up) resulting from certain mutations, and the critical disconnect between in vitro resistance assays and in vivo evolution. Ultimately, we highlight how the formidable barrier of phage resistance can be converted into a therapeutic gain, thereby offering a robust framework for sustainable phage therapy.
    Keywords:  antimicrobial resistance; bacteriophage; evolved phages; infection control; phage resistance
    DOI:  https://doi.org/10.3389/fimmu.2026.1856088
  2. BMC Microbiol. 2026 Jul 17. pii: 648. [Epub ahead of print]26(1):
      The rapid rise of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) poses a serious threat in healthcare settings, as these bacteria can cause infections that are untreatable with conventional antibiotics. This crisis has driven the search for alternative therapies, one of which is bacteriophages. In this study, we isolated a novel bacteriophage, vB_AbaM_EA1 (E7 for short), from wastewater and evaluated its potential activity against clinical MDR A. baumannii strains. Phage E7 successfully infects (27.5%) of the 40 clinical MDR A. baumannii isolates we tested. Laboratory characterization suggested that E7 is a highly efficient lytic phage, rapidly attaching to bacterial cells and producing 1000 new viral particles.A key finding was its potent activity against bacterial biofilms, a major source of persistent infections. Not only did Phage E7 effectively prevent the formation of new biofilms, but more importantly disrupted mature ones, which typically confer higher resistance to antibiotics.Genome sequencing confirmed that Phage E7 is a new member of the Obolenskvirus genus and that its genome lacks genes encoding bacterial toxins, antibiotic resistance, or lysogenic factors, indicating a mandatory safety profile for therapeutic use. Furthermore, E7 remained stable across a broad temperature range (-20 to 45 °C) and pH values (5-9) that it might encounter during storage and administration. In conclusion, Phage E7 is a stable, safe, and highly effective candidate for phage therapy against infections by MDR A. baumannii. Its ability to target both planktonic bacteria and biofilms makes it a promising candidate for future development into clinical applications.
    Keywords:   Acinetobacter baumannii ; Antimicrobial resistance; Bacteriophage; Genomic analysis; Multidrug-resistant; Phage therapy
    DOI:  https://doi.org/10.1186/s12866-026-05262-7
  3. Front Immunol. 2026 ;17 1854213
       Background: The oral cavity harbors a dynamic microbial ecosystem that interacts with epithelial barriers, host immunity, and local tissue environments. Disruption of this balance is increasingly recognized as a key driver of major oral diseases, including periodontitis, dental caries, and oral squamous cell carcinoma (OSCC). However, the biological links between microbial ecology, immune regulation, and disease progression are insufficiently integrated, limiting mechanistic understanding and translational progress.
    Methods: This structured narrative review searched PubMed/MEDLINE, Web of Science, Embase, and Scopus for relevant studies on oral microbiome ecology, mucosal immunity, dysbiosis, oral diseases, and emerging therapies. Evidence was narratively synthesized across microbiome ecology, mucosal immunology, disease pathogenesis, and translational research, with consideration of study type, mechanistic relevance, and translational significance.
    Results: Current evidence supports that oral homeostasis relies on coordinated interactions among commensal microbial communities (CMC), epithelial and salivary barriers, and immune surveillance. Dysbiosis disrupts this equilibrium by promoting the expansion of pathobionts, amplifying inflammatory responses, and contributing to tissue injury. This systems-level perspective helps explain the persistence and heterogeneity of oral diseases beyond pathogen-centered models. Emerging technologies are reshaping this field. These include microbiome-modulating therapies, host-directed interventions, multi-omics approaches, and artificial intelligence (AI). These approaches are advancing disease stratification, biomarker discovery, and precision therapeutic development.
    Conclusion: Oral diseases should be understood as disorders of host-microbiome-immune disequilibrium rather than as isolated infections. This perspective highlights the need for integrated strategies that consider microbial ecology, immune regulation, epithelial barrier function, and clinical context to improve prevention, diagnosis, and treatment in precision oral medicine.
    Keywords:  dysbiosis; host-microbiome interactions; immune homeostasis; oral microbiome; oral mucosal immunity; precision oral medicine
    DOI:  https://doi.org/10.3389/fimmu.2026.1854213
  4. NPJ Antimicrob Resist. 2026 Jul 14.
      The rapid rise of multidrug-resistant bacterial pathogens has renewed interest in bacteriophage therapy, yet bacterial resistance to phages can evolve rapidly. Two evolutionary strategies have been proposed to address this challenge: coevolutionary phage training, which adapts phages to anticipated resistance mechanisms, and phage-antibiotic synergy, which exploits tradeoffs between phage resistance and antibiotic susceptibility. Here, we show that these strategies intersect in complex but predictably exploitable ways. Using Escherichia coli and bacteriophage λ, we demonstrate that resistance to a trained-but not an untrained-phage generates collateral sensitivity to erythromycin and rifampicin, but not to five other antibiotics. This training-induced synergy is mechanistically linked to repeated disruption of lpcA, a gene involved in lipopolysaccharide core biosynthesis. Leveraging this mechanistic insight, we successfully predicted that novobiocin and rifapentine would also exhibit collateral sensitivity with a trained λ phage. We further show that incorporating sub-lethal erythromycin during phage training reshapes coevolutionary trajectories, increasing the frequency with which phages evolve the ability to use a second host receptor and thereby enhancing bacterial suppression. Together, these results reveal that despite the inherent complexity of phage-bacteria coevolution, key outcomes can be anticipated and directed. Our findings highlight the promise of evolution-informed, predictive strategies for designing therapies.
    DOI:  https://doi.org/10.1038/s44259-026-00249-w
  5. J Appl Microbiol. 2026 Jul 14. pii: lxag174. [Epub ahead of print]
       AIMS: Bacteriophage (phage) propagation has traditionally relied on bacterial culture media containing animal-derived ingredients; however, safety concerns with animal-derived materials for production of phages for therapeutic use limit their acceptability. We compared animal-free and traditional media formulations, and evaluated effects on phage yield, bactericidal activity, and genomic characteristics, hypothesizing no significant differences would be observed.
    METHODS AND RESULTS: Phages targeting Pseudomonas aeruginosa (n = 8) and Staphylococcus aureus (n = 1) were propagated in solid and liquid media containing animal-free (AF) or animal-derived (LB) peptones. Kinetic assays were used to assess phage suppression of host bacterial growth. Whole genome sequencing of phages and their bacterial hosts propagated in AF or LB broth was used to observe genomic differences between media formulations. In a mock therapeutic phage screen, spot tests, efficiency of plating (EOP) and kinetic assays were performed against non-host bacterial targets. Animal-free peptone did not impact phage yield, with both AF and LB phage stocks growing to high titers (≥108 PFU mL-1). Kinetic assay results showed similar suppression indices for AF and LB-grown phages. Comparisons of phage and bacterial genome annotations showed no major differences arising from media formulation. Spot test, EOP, and kinetic assay results in phage susceptibility tests were similar between AF and LB phages.
    CONCLUSIONS: Findings suggest animal-free peptones do not alter phage yield, bactericidal activity, or genomic characteristics, supporting use of animal-free medium for medicinal phage manufacture. This is one of the first studies to systematically combine phenotypic and genomic assessment of phages and hosts across animal-free and traditional media.
    Keywords:  antimicrobial resistance; bacteriophages; biopharmaceuticals; bioprocessing; medical microbiology
    DOI:  https://doi.org/10.1093/jambio/lxag174
  6. Cureus. 2026 Jun;18(6): e110757
       BACKGROUND: Periodontitis and oral squamous cell carcinoma (OSCC) are chronic inflammatory conditions linked to systemic health and share biological pathways involving immune dysregulation, oxidative stress, and tissue destruction.
    AIM: The aim of the study is to evaluate and compare salivary chemerin and matrix metalloproteinase-9 (MMP-9) levels among healthy individuals, periodontitis patients, and OSCC patients, and to assess their potential diagnostic utility.
    MATERIALS AND METHODS: A cross-sectional study was conducted on 90 participants divided into three groups (n = 30 each): healthy controls, periodontitis patients, and OSCC patients. Unstimulated saliva samples were obtained and analyzed for chemerin and MMP-9 using enzyme-linked immunosorbent assay (ELISA). Periodontal parameters, including oral hygiene index-simplified (OHI-S), Russell's index, probing pocket depth (PPD), and clinical attachment loss (CAL), were recorded. Analysis of variance (ANOVA), Tukey's post hoc test, and Pearson correlation were used for statistical analysis.
    RESULTS: Salivary chemerin and MMP-9 levels were significantly elevated in both periodontitis and OSCC patients compared to healthy individuals, with the highest levels observed in the OSCC group. MMP-9 demonstrated a stronger association with periodontal tissue destruction. Analysis revealed a direct association between chemerin and MMP-9 concentrations.
    CONCLUSION: Salivary chemerin and MMP-9 levels were significantly higher in periodontitis and OSCC patients than in healthy individuals, with the highest levels observed in the OSCC group. Elevated biomarker levels were associated with worsening periodontal parameters, indicating their role in inflammation, tissue destruction, and tumor progression. These findings suggest a possible inflammatory link between periodontitis and OSCC and support the potential of salivary chemerin and MMP-9 as non-invasive biomarkers for disease diagnosis and monitoring.
    Keywords:  chemerin; mmp-9; oral squamous cell carcinoma; periodontitis; salivary biomarker
    DOI:  https://doi.org/10.7759/cureus.110757
  7. Front Cell Infect Microbiol. 2026 ;16 1864022
      Oral diseases and placental disorders are closely associated with adverse pregnancy outcomes, and accumulating evidence supports their crosstalk that constitutes the "oral-placental axis". This study integrated scientometric and bioinformatic approaches to systematically analyze global research trends, collaboration networks, research hotspots, and core molecular-microbial mechanisms of the oral-placental axis covering the period from 2016 to 2025. A total of 196 eligible publications were retrieved from the Web of Science Core Collection, Scopus, and PubMed. Bibliometric visualization was performed using VOSviewer, CiteSpace, and R-bibliometrix, and bioinformatic analysis was conducted to identify shared genes, signaling pathways, and microbial links between oral and placental diseases. The results revealed an annual publication growth rate of 5.03%, with the United States, China, and Australia as major contributing countries, the University of Queensland as the leading institution, and Gomez-Arango Luisa F. and Nitert Marloes Dekker as the most influential authors. Core keywords included preterm birth, periodontal diseases, gestational diabetes mellitus, and oral microbiome, reflecting a research shift from phenotypic association to mechanistic exploration such as microbial vertical transmission and inflammatory signaling. Mechanistic analyses identified shared hub genes (e.g., KRT19, ADAMDEC1, AQP9, SPAG4, PLAT) and key pathways, predominantly primary immunodeficiency and complement and coagulation cascades. Pathogenic bacteria including Fusobacterium nucleatum and Porphyromonas gingivalis mediated adverse pregnancy outcomes via hematogenous spread and placental barrier disruption. This study established a bidirectional regulatory model of the oral-placental axis involving shared risks, microbial transmission, and systemic inflammation, providing a theoretical basis for preconception oral intervention and precise prevention during pregnancy, and supporting the integration of oral care into routine perinatal management.
    Keywords:  adverse pregnancy outcomes; conceptual evolution; knowledge graph; molecular mechanisms; oral-placental axis; periodontal diseases; research trends; scientometrics
    DOI:  https://doi.org/10.3389/fcimb.2026.1864022
  8. Int Wound J. 2026 Jul;23(7): e70982
      Diabetic foot ulcers are among the most challenging complications of diabetes. Diabetes heightens patients' risk of severe complications, including amputations and death, while also driving up healthcare system costs. Given the significance of this problem, the present study conducted a systematic review of studies that used Classical Statistical and Machine Learning Approaches to identify factors influencing the development of diabetic foot ulcers in individuals with diabetes. A thorough literature search was conducted in PubMed, Scopus and Web of Science, covering their inception through 7 September 2025. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMAs) guidelines. Data were analysed narratively using content analysis. Eligible studies used predictive methods to identify factors associated with the development of diabetic foot ulcers. A total of 4396 articles were screened, and 66 studies were selected for full-text review after application of the inclusion and exclusion criteria. The review of these studies identified 95 factors associated with predicting diabetic foot ulcers, among which neuropathy, diabetes duration, age, body mass index and peripheral vascular disease were the most frequently reported. In addition, among the predictive models used in the studies, logistic and Cox regression models were the most useful for predicting factors associated with diabetic foot ulcers. This study identifies key predictive factors for diabetic foot ulcers, enabling healthcare systems to target high-risk patients through early screening. Proactive identification of vulnerable diabetic patients can prevent severe complications, such as amputation.
    Keywords:  diabetes mellitus; diabetic foot; machine learning; systematic review
    DOI:  https://doi.org/10.1111/iwj.70982
  9. Wound Repair Regen. 2026 Jul-Aug;34(4):34(4): e70187
      Chronic and complex wounds represent a major clinical and economic burden, requiring frequent assessment, early detection of complications, and accurate prediction of healing outcomes. Conventional wound evaluation is often subjective and time-intensive, motivating the development of automated approaches. Machine learning (ML) has emerged as a powerful tool for wound management by enabling wound detection, segmentation, tissue characterisation, infection assessment, and healing prediction using wound images, clinical records, and sensor-derived data. This structured narrative review summarises key ML and deep learning (DL) methods applied in wound care, including commonly used architectures, data modalities, and evaluation strategies. We critically discuss persistent barriers limiting clinical adoption, such as limited dataset size and diversity, annotation inconsistency, poor generalizability, bias, lack of external and prospective validation, and challenges related to privacy, regulation, and clinical workflow integration. Finally, we highlight emerging opportunities including multimodal learning, self-supervised learning, federated learning, explainable AI (XAI), and mobile or wearable technologies for continuous wound monitoring. Overall, ML has strong potential to improve the objectivity, efficiency, and personalization of wound care; however, clinically deployable solutions will require standardised datasets, transparent reporting, rigorous validation, and interdisciplinary collaboration.
    Keywords:  chronic wounds; clinical decision support; deep learning; explainable artificial intelligence; machine learning; wound image analysis; wound management
    DOI:  https://doi.org/10.1111/wrr.70187
  10. Microbiologyopen. 2026 Aug;15(4): e70353
      Oral candidiasis is the most prevalent fungal infection of the oral cavity and is frequently associated with immunosuppression. Although traditionally classified as a superficial condition, growing evidence suggests that oral infection with Candida sp. in a susceptible host may disseminate and evolve into invasive candidiasis, such as bloodstream infection (candidemia), one of the leading nosocomial infections associated with high mortality. This review addresses the clinical manifestations of oral candidiasis, local and systemic risk factors, and the emerging role of non-albicans Candida and related yeasts in the pathogenesis of both candidiasis and candidemia. Furthermore, we revisit antifungal resistance, the interaction between Candida albicans and the oral microbiome, and the potential impact of these interactions on progression to invasive infection. Animal models of oral candidiasis and candidemia are also considered, highlighting their relevance for understanding virulence mechanisms and for developing new therapeutic strategies. In an integrative way, this review summarizes current evidence on the relationship between oral candidiasis and candidemia, emphasizing the importance of early diagnosis, prevention, and the search for alternative therapies in light of antifungal resistance.
    Keywords:  Candida spp.; antifungal resistance; candidemia; oral candidiasis; oral microbiome
    DOI:  https://doi.org/10.1002/mbo3.70353
  11. Molecules. 2026 Jun 24. pii: 2229. [Epub ahead of print]31(13):
      Chronic wounds represent a substantial and growing clinical burden, yet durable healing remains difficult to achieve in a large proportion of patients. The skin microbiome plays a central role in this challenge: in healthy tissue, resident microorganisms support barrier integrity and calibrate immune responses, whereas in chronic wounds, community disruption-often combined with persistent biofilm formation-drives non-resolving inflammation, impairs re-epithelialisation, and increases antimicrobial tolerance. As antibiotic resistance escalates, these features strengthen the rationale for microbiome-directed strategies that target wound ecology while reducing reliance on conventional antimicrobials. Current evidence is still dominated by mechanistic and preclinical studies, with only early clinical signals for selected approaches; therefore, next-generation probiotics, including Lactiplantibacillus/Lactobacillus spp., as well as defined prebiotic and postbiotic formulations, should be interpreted as promising adjuncts rather than clinically established therapies. Causal mechanisms, optimal formulations, reproducibility, and patient-level determinants of response remain insufficiently defined, representing a critical knowledge gap that limits translation. Here, we synthesise current evidence linking microbial ecology to key wound-healing pathways and propose a precision framework that integrates metagenomics, transcriptomics, metabolomics, and spatial profiling to map host-microbe interactions, identify predictive biomarkers, and guide stratified therapy. We further highlight combinatorial approaches pairing ecological engineering with biofilm-disruptive materials and immune-modulatory molecules. Realising the potential of these interventions will require mechanism-resolved clinical trials, standardised outcome frameworks, and patient stratification tools-advances that could improve chronic wound management while reducing selective pressure for antimicrobial resistance.
    Keywords:  biofilms; chronic wounds; human microbiome; microbial metabolites; microbiome-targeted molecules; postbiotics; prebiotics; probiotics; wound healing
    DOI:  https://doi.org/10.3390/molecules31132229
  12. Microbiol Spectr. 2026 Jul 13. e0060126
      Mutation-specific cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved clinical outcomes for people with CF (pwCF), yet its impact on the nasal microbial metagenome remains insufficiently understood. This prospective, post-approval study investigated the impact of 15-week ETI therapy on sinonasal microbiota of pwCF aged 12 years and older. Whole-genome shotgun sequencing was performed on total DNA from 24 paired nasal lavage samples, with synthetic spike-in controls enabling absolute abundance normalization. Taxonomic profiling was conducted using the Wochenende pipeline. ETI did not induce major shifts in alpha or beta diversity. Instead, the overall microbial community became further dominated by the skin commensals Staphylococcus epidermidis and Cutibacterium acnes, accompanied by a more than twofold increase in total bacterial load. Classical CF pathogens showed divergent trajectories: Pseudomonas aeruginosa tended to decrease, whereas Staphylococcus aureus exhibited a tendency toward increased abundance. Co-occurrence network analysis revealed a transition from a dense, multicomponent baseline network to a single, fully connected, but less densely integrated network following treatment initiation.IMPORTANCEThe nasal cavity represents the primary entry point of microorganisms into the respiratory tract and a potential reservoir for lower airway infection, the major cause of CF disease progression. Using shotgun metagenomics with spike-in controls, this study provides the first genome-wide characterization of how ETI alters microbial load and pathogen dynamics in CF nasal airways. Treatment with ETI strengthened the dominance of skin commensals in the nares while reducing P. aeruginosa. Given the observed increase in S. aureus, further work is needed to determine whether this represents expansion of a typical nasal colonizer or a clinically relevant rise of a key CF pathogen that could act as a reservoir for future lower airway infection.
    Keywords:  CFTR modulation; ELX/TEZ/IVA; cystic fibrosis; metagenomics; nasal metagenome; whole-genome sequencing
    DOI:  https://doi.org/10.1128/spectrum.00601-26
  13. Mob DNA. 2026 Jul 16.
       BACKGROUND: The global rise of multidrug resistant (MDR) ESKAPE pathogens represents a serious threat to antimicrobial therapy. While phage therapy has re-emerged as a promising alternative, its effectiveness may be compromised by bacterial defense systems, particularly those encoded on plasmids. Comprehensive surveillance of the distribution, diversity, and mobilome context of plasmid-encoded defense systems in ESKAPE pathogens remains key to the design of effective phage therapies.
    RESULTS: We analyzed 7,330 dereplicated plasmids from ESKAPE pathogens to characterize the prevalence, diversity, and co-occurrence of plasmid-encoded antiphage defense systems. Conjugative plasmids, especially from Enterobacter spp. and K. pneumoniae, harbored the highest prevalence and diversity of defense systems. Defense-positive plasmids showed larger sizes, higher GC content, and frequent co-occurrence of resistance genes, especially from β-lactam, aminoglycoside, and sulfonamide classes, along with transposable elements such as IS6, IS3, and Tn3. Random forest and correlation analyses confirmed TEs and ARGs as dominant predictors of defense system occurrence. Network analysis revealed structured and partially conserved interactions among defense genes, TEs, and ARGs. RM and CBASS systems were frequently linked to beta-lactam and aminoglycoside resistance genes, as well as TEs such as IS6 and IS3. Recurrent associations such as RM-IS6, RM-IS1380, CBASS-IS3 and RM-OXA suggest shared horizontal transfer mechanisms.
    CONCLUSIONS: Plasmid-encoded antiphage defense systems in ESKAPE pathogens are widespread, structured, and linked to ARGs and mobile genetic elements. These findings highlight the contribution of plasmids to the dissemination of phage-resistance traits, underscore the importance of the mobilome in shaping phage-resistance landscapes in multidrug-resistant pathogens, and support the incorporation of plasmid defense profiling into phage therapy design.
    Keywords:  Abortive infections; Antiphage defensive systems; CRISPR-Cas; Conjugative; DNA modification system; ESKAPE pathogens; Mobilizable; Multi-drug resistance; Non-mobilizable; Restriction modification
    DOI:  https://doi.org/10.1186/s13100-026-00410-2
  14. Mol Biol Rep. 2026 Jul 15. pii: 1172. [Epub ahead of print]53(1):
      Urinary tract infections (UTIs) are among the most prevalent bacterial infections worldwide, accounting for a major clinical impact due to high recurrence rates, microbial diversity, biofilm formation, polymicrobial contribution and the rapid emergence of antimicrobial resistance (AMR). Traditional culture-based diagnostic approaches are constrained by high turnaround times and insufficient resolution of virulence and resistance factors, frequently result in empirical antibiotic therapy. Recent breakthroughs in molecular biology and biotechnology have fuelled the advancement of innovative diagnostic approaches for the quick, sensitive and pathogen-specific detection of uro-pathogens. Rapid pathogen identification and antibiotic susceptibility testing are critically needed for the effective targeted antibiotic therapy. This paper initially examines promising technologies employing machine learning models to provide rapid diagnostic outcomes, specifically for urinary tract infections. This paper focuses on promising molecular diagnostic technologies such as nucleic acid amplification, biosensor-based platforms, microfluidic lab-on-chip systems and omics-based approaches, along with their amalgamation with Artificial intelligence (AI) and smart diagnostics. Improved diagnostic precision, recommendations for targeted antimicrobial therapy and support for antimicrobial resistance surveillance and management are among the translational applications of these developments that are highlighted. Challenges related to medical ethics, execution and regulations are also covered. The combined efforts of next-generation and AI-assisted diagnostic tools offer a revolutionary paradigm for accurate and efficient antibiotic resistance control to treat UTIs.
    Keywords:  Antimicrobial resistance; Artificial intelligence (AI); Molecular diagnostics; Precision medicine; Smart system; Urinary tract infections
    DOI:  https://doi.org/10.1007/s11033-026-12344-2
  15. Arch Virol. 2026 Jul 16. pii: 227. [Epub ahead of print]171(8):
      Multidrug-resistant (MDR) Klebsiella infections pose a significant challenge and necessitate alternative antimicrobial approaches. Bacteriophage therapy represents a promising option; however, therapeutic outcomes depend on phage dose, dosing strategy, and host-pathogen interactions. In this study, we isolated and characterized a lytic Klebsiella phage, vB_KpnS_TRK61 (TRK61), from municipal wastewater. Electron microscopy revealed that TRK61 has an icosahedral head and a long, flexible tail, consistent with members of the family Demerecviridae. Host range analysis demonstrated lytic activity against clinical isolates of Klebsiella pneumoniae and K. oxytoca, as well as K. quasipneumoniae ATCC 700,603 and K. michiganensis ATCC 43,086. Genome sequencing revealed a 113,941 bp double-stranded DNA genome encoding 147 predicted proteins and 24 tRNA genes, with no identifiable antibiotic resistance, toxin, or virulence-associated genes. One-step growth experiments indicated a latent period of approximately 30 min and a burst size of ~ 50 plaque-forming units per infected cell. The in vivo efficacy of TRK61 was evaluated using the Galleria mellonella infection model at multiplicities of infection (MOIs) of 10, 100, and 1,000 under single- and double-dose regimens. Phage-mediated protection was strongly influenced by both MOI and dosing frequency. Moderate MOIs combined with repeated dosing produced the highest survival rates, whereas excessively high MOIs occasionally reduced efficacy. Overall, TRK61 shows strong lytic activity and in vivo efficacy, supporting its potential as a therapeutic or biocontrol agent against MDR Klebsiella.
    DOI:  https://doi.org/10.1007/s00705-026-06693-3
  16. Wound Repair Regen. 2026 Jul-Aug;34(4):34(4): e70189
      Diabetic foot ulcers (DFUs) are the leading cause of amputations in people with diabetes, mainly due to poor wound healing. This study evaluated DFU trial designs and analysed observational data from the two prospective Diabetic Foot Consortium (DFC) studies to estimate longitudinal healing and amputation rates, assess the effects of wound surface area and duration on healing, and inform sample size considerations for future trials. We analysed data from Open Wound Master Protocol (MP, n = 419) and c-Myc Biomarker (n = 140). The primary outcome was complete wound healing. Time-to-event analysis estimated healing and amputation rates, with amputations classified as non-healed. Logistic regression assessed the prediction of healing based on baseline wound characteristics, with model performance evaluated using AUC (area under the curve). Sample size calculations were performed to achieve 80% power. In the MP study, healing rates were 26% by week 12% and 49% by week 32; amputation rates were 4% and 10%, respectively. The c-Myc study showed 38% healing and 2.5% amputation by week 12. Wound area and duration significantly predicted healing (AUC ≥ 0.70 by 24 weeks). For smaller treatment effects, predicted healing rates varied by up to 40% between small and large wounds, impacting sample size. Contemporary DFU trial designs and healing times remained largely unchanged over two decades. While shorter trials (e.g., 12 weeks) theoretically require smaller sample sizes due to reduced outcome variance, they risk failing to capture the full treatment effect. Trial design must account for baseline wound characteristics, which should inform eligibility criteria and follow-up.
    Keywords:  amputation; biomarkers; clinical trials; diabetic foot ulcers; predictive modeling; wound healing
    DOI:  https://doi.org/10.1111/wrr.70189
  17. Clin Oral Investig. 2026 Jul 17. pii: 343. [Epub ahead of print]30(8):
       OBJECTIVE: The aim of the study was to evaluate the association between T. tenax and E. gingivalis with peri-implant and periodontal diseases compared to healthy controls.
    MATERIAL AND METHODS: A total of 140 participants were included in four groups in this study. The groups included 35 patients with peri-implantitis and periodontitis (IP+P group); 35 patients with peri-implant and periodontal health (IH+PH group); 35 patients with periodontitis (P group), and 35 periodontally healthy individuals (PH group). Clinical periodontal and peri-implantitis parameters were recorded. Plaque samples were taken from around teeth in P and PH groups and around implants and teeth in IP+P and IH+PH groups. The presence of T. tenaxandE. gingivalis was determined under a microscope.
    RESULTS: The detection of T. tenax and E. gingivalis parasites in tooth samples was higher in the IP+P and P groups than in the IH+PH and PH groups (p<0.001). Both parasites were detected more frequently in peri-implant samples in the IP+P group than in the IH+PH group (p<0.001 and p=0.001, respectively). There was no difference in parasite detection between tooth and peri-implant samples in the same host in the IP+P and IH+PH groups (p³0.05). The presence of T. tenax andE. gingivalis was associated with the presence of periodontal disease, and severity and grading of periodontitis independently of other factors (p<0.05).
    CONCLUSION: The presence of T. tenax and E. gingivalis might be associated with peri-implantitis and periodontitis lesions. The detection of parasites is similar on tooth and implant surfaces in the same mouth.
    CLINICAL RELEVANCE: Protozoa found at sites of disease may not imply a direct causal relationship with the disease; nevertheless, their detection can indicate opportunistic microbial activity or ongoing oral inflammation.
    Keywords:  Entamoeba gingivalis; Periimplantitis; Periodontitis; Trichomonas tenax
    DOI:  https://doi.org/10.1007/s00784-026-07036-x
  18. J Clin Med. 2026 Jun 28. pii: 5044. [Epub ahead of print]15(13):
      Background/Objectives: Periodontitis reflects a dysregulated inflammatory response in which impaired resolution and efferocytosis may play a central role. The TAM receptor MerTK and its ligand growth arrest-specific-6 (Gas6) are key regulators of these processes; however, their profile in gingival crevicular fluid (GCF) across the periodontal disease spectrum remains unclear. This cross-sectional study aimed to evaluate GCF levels of Gas6 and soluble MerTK (sMerTK) in individuals with periodontal health, gingivitis, and periodontitis, and to examine their associations with clinical periodontal parameters. Methods: Eighty-one systemically healthy adults were enrolled into three groups: periodontal health, gingivitis, and periodontitis. Full-mouth clinical periodontal measurements were recorded. Gas6 and sMerTK levels were quantified by enzyme-linked immunosorbent assay. Results: sMerTK progressively decreased from periodontal health to gingivitis and periodontitis, with significant differences among all groups (p < 0.001). Gas6 total amount was higher in the diseased groups, whereas its concentration decreased. The Gas6/sMerTK ratio increased stepwise with disease severity (p < 0.001), showing positive correlations with clinical attachment loss and other clinical periodontal parameters, while sMerTK showed inverse correlations. Conclusions: These findings suggest that the local GCF Gas6/sMerTK balance is altered across periodontal states, primarily due to a marked reduction in sMerTK. The Gas6/sMerTK ratio may represent a potential exploratory indicator of periodontal inflammatory status, although longitudinal validation is required.
    Keywords:  Gas6; MerTK; TAM receptors; efferocytosis; gingival crevicular fluid; periodontitis; resolution of inflammation
    DOI:  https://doi.org/10.3390/jcm15135044
  19. BMC Microbiol. 2026 Jul 14.
      Klebsiella pneumoniae (K. pneumoniae) is a critical pathogen responsible for a wide range of severe infections. Its escalating resistance to frontline antimicrobials, particularly carbapenems, severely compromises existing therapeutic options and undermines current treatment strategies. This clinical challenge is further exacerbated by the emergence of multidrug-resistant (MDR) strains and hypervirulent lineages, which substantially complicate infection management and worsen patient outcomes. Ultimately, this alarming convergence of resistance and virulence presents a severe public health threat that necessitates the urgent development of novel therapeutic approaches; in this regard, phage therapy is emerging as a promising strategy. Bacteriophages and their derivatives have garnered increasing recognition as targeted antibacterial agents, demonstrating potent activity against carbapenemase producing and MDR K. pneumoniae in vitro models. They effectively lyse MDR strains, disrupt biofilm formation, and have shown promising therapeutic efficacy across various in vivo models. To ensure safety in clinical applications, genome sequencing is essential to identify and exclude undesirable genes, thereby determining therapeutic suitability. Here, we have sequenced and analyzed the genomic characteristics of seven lytic bacteriophages targeting carbapenemase-producing MDR K. pneumoniae. Genomic evaluation confirmed that these phages are strictly lytic and revealed the presence of distinct lysis modules across the genomes. Phylogenetic analysis showed that these phages cluster within four genera of Caudoviricetes: Taipeivirus, Drulisvirus, Przondovirus, and Webervirus. The phage genomes ranged from 15,773 to 166,437 base pairs (bp) in length and encoded core structural and replication modules. Furthermore, distinct lytic modules predicted to have function in bacterial capsule degradation were identified across the genomes. Importantly, the absence of known virulence or toxin genes guarantees therapeutic safety and satisfies rigorous genomic criteria for clinical translation. These findings underscore the potential of these phages as a promising alternative for combating MDR and hypervirulent K. pneumoniae infections. Future in vivo investigations and clinical trials are essential to validate their therapeutic efficacy, safety profile, and optimal treatment protocols.
    Keywords:  Carbapenemase; Genomic characterization; Klebsiella pneumoniae; Multidrug resistant; Phage therapy
    DOI:  https://doi.org/10.1186/s12866-026-05410-z
  20. J Clin Med. 2026 Jul 07. pii: 5296. [Epub ahead of print]15(13):
      This narrative review synthesizes evidence linking periodontal dysbiosis with Alzheimer's disease, all-cause dementia, and dementia-relevant mechanisms, focusing on the red complex pathogens P. gingivalis, T. denticola, and T. forsythia and on the translational meaning of periodontal therapy. A PubMed-centered literature search up to May 2026 informed this synthesis (a narrative review, not a registered systematic review or meta-analysis) of 46 periodontal-scope sources, supplemented by five contextual references identified outside the periodontal search (51 references in total). P. gingivalis shows the strongest mechanistic support, including gingipains, lipopolysaccharide, outer membrane vesicles, endothelial stress, and neuroinflammatory signaling; T. denticola shows moderate biological plausibility; and T. forsythia remains mainly hypothesis-generating. Human studies associate periodontitis, tooth loss, oral-hygiene indicators, and periodontal-care exposure with dementia-relevant outcomes, but residual confounding, reverse causation, dental-care access, and heterogeneous endpoints preclude causal inference. Notably, direct targeting of a single periodontal pathogen has not shown clinical benefit, as the gingipain inhibitor atuzaginstat failed in the GAIN trial, contrasting with the modest success of amyloid-targeting therapies. Current evidence supports graded plausibility rather than causal certainty, and a registered multi-database systematic review with neurological endpoints is needed before meta-analytic clinical claims can be made.
    Keywords:  Alzheimer’s disease; Porphyromonas gingivalis; dementia; periodontal dysbiosis; periodontitis; red complex pathogens
    DOI:  https://doi.org/10.3390/jcm15135296
  21. J Clin Med. 2026 Jun 24. pii: 4922. [Epub ahead of print]15(13):
      Background/Objectives: This study aimed to evaluate the gingival crevicular fluid (GCF) levels of fractalkine/CX3CL1 and CX3CR1 in patients with gingivitis and periodontitis before and after non-surgical periodontal therapy. Methods: A total of 90 individuals comprising 30 with stage 3 periodontitis, 30 with gingivitis, and 30 periodontally healthy, were enrolled in the study. Gingivitis and periodontitis patients underwent non-surgical periodontal treatment. GCF samples were collected at baseline and at 1 and 3 months after treatment. CX3CL1 and CX3CR1 were measured by an ELISA analysis. Results: GCF CX3CL1 and CX3CR1 were significantly elevated in patients with periodontitis and gingivitis compared to healthy controls (p < 0.001). The periodontitis patients also showed higher GCF levels of CX3CL1 and CX3CR1 than those with gingivitis (p < 0.001). Significant decreases in GCF CX3CL1 and CX3CR1 were detected at 1 month after periodontal treatment compared to baseline values in both the gingivitis and periodontitis patients (p < 0.001). Moreover, the periodontitis patients exhibited significant decreases in both CX3CL1 and CX3CR1 levels at 3 months post-treatment compared to 1 month (p < 0.001), whereas no significant changes were observed between the two time points in the gingivitis patients (p > 0.05). Conclusions: Our findings suggest that the CX3CL1-CX3CR1 axis might contribute to the inflammatory processes of periodontal diseases and may represent a treatment-responsive component of the local host response.
    Keywords:  CX3CL1; CX3CR1; fractalkine; gingival crevicular fluid; gingivitis; periodontal treatment; periodontitis
    DOI:  https://doi.org/10.3390/jcm15134922
  22. BMC Genomics. 2026 Jul 11.
       BACKGROUND: Staphylococcus epidermidis is a major cause of orthopaedic device-related infections (ODRIs), which are often challenging to treat due to their extensive antimicrobial resistance (AMR) and biofilm formation. It has been hypothesised that S. epidermidis may rapidly adapt to the medical device niche, enhancing persistence, but direct evidence of within-host pathoadaptive evolution remains limited.
    RESULTS: To investigate within-host evolution during chronic infection by S. epidermidis, we analysed isolates from patients with confirmed ODRIs and used a rat infection model to examine the evolution of strains from two distinct epidemic lineages (ST2 and ST23). Our analysis revealed that the replicative transposition of insertion sequence (IS) elements within the accessory genome was the predominant mechanism of genetic diversification. This was largely driven by the IS256 family, which accounted for approximately 25% of all mutational events. However, other than SCCmec deletions resulting in the loss of mecA, no mutations, including those which exhibited parallel evolution, were predicted or observed to influence AMR or biofilm formation. These findings suggest that the strains investigated in this study, which already exhibited high-level multidrug resistance and biofilm-forming ability, were likely pre-adapted epidemic S. epidermidis clones well suited to establishing persistent ODRIs.
    CONCLUSIONS: Our findings highlight the prominent role of IS elements in driving genetic diversification in S. epidermidis, underscoring the need for closer examination of their contribution to pathoadaptation during persistent infection.
    Keywords:   Staphylococcus epidermidis ; Antimicrobial resistance (AMR); Biofilm; IS256 ; Insertion sequence (IS) elements; Orthopaedic device-related infections (ODRIs); Pathoadaptation; Staphylococcal cassette chromosome mec (SCCmec); Within-host evolution
    DOI:  https://doi.org/10.1186/s12864-026-13148-1
  23. Microbiol Res. 2026 Jul 14. pii: S0944-5013(26)00202-8. [Epub ahead of print]312 128638
      Ginger bacterial wilt, caused by the Ralstonia solanacearum species complex (RSSC), is a devastating soil-borne disease threatening global production. This study developed a novel synergistic biocontrol strategy by combining a broad-spectrum phage cocktail with phage-carrier biocontrol bacteria (PCBB). A highly effective phage cocktail (pRS2401, pRS2405, pRS2406, pRS2410, and pRS2411), formulated against a pathogenic RSSC mix, demonstrated superior environmental stability and lytic efficacy over individual phages in ex vivo leaf assays. A PCBB strain (Bacillus subtilis BS1), selected for its dual functionality of direct antagonism and enhanced phage dispersal, was combined with the phage cocktail. In soil and pot experiments, this combination exhibited significant synergistic effects, drastically reducing the pathogen load and improving plant health, with ginger rhizome weight approaching healthy control levels. These results underscore the potential of combining phages with carrier bacteria as an effective and sustainable strategy for managing soil-borne bacterial diseases.
    Keywords:  Biocontrol; Broad-spectrum bacteriophage; Ginger bacterial wilt; Phage-bacteria synergy; Ralstonia solanacearum species complex
    DOI:  https://doi.org/10.1016/j.micres.2026.128638
  24. J Tissue Viability. 2026 Jul 10. pii: S0965-206X(26)00050-1. [Epub ahead of print]35(4): 101032
       AIM: The aim was to evaluate the impact of topical insulin therapy vs normal saline on wound healing in adults with diabetic foot ulcers.
    BACKGROUND: Diabetic foot ulcers are among the most debilitating complications of diabetes, associated with high morbidity, risk of amputation, and significant healthcare costs. Insulin, beyond its glycaemic effects, exhibits regenerative and angiogenic properties that may support wound healing when applied topically.
    MATERIALS AND METHODS: A systematic review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA 2020 guidelines. A literature search was conducted across a number of databases, including MEDLINE, CINAHL, PubMed, EMBASE, and clinical trial registries. Only randomised controlled trials (RCTs) comparing topical or locally injected insulin with standard wound care in adult diabetic patients were eligible. Risk of bias was assessed using the Cochrane RoB 1.0 tool. Meta-analyses were conducted using Review Manager (RevMan) 5.4, employing a random-effects model. The certainty of the evidence was assessed using the GRADE process.
    RESULTS: Sixteen RCTs met the inclusion criteria. No study reported the number of wounds healed. Meta analysis of 2 studies demonstrated that topical insulin therapy was associated with a statistically significant reduction in time to wound healing (MD: -6.05 days, 95% CI: -7.55 to 4.55; p < 0.00001), in favour of the insulin group. A narrative analysis of 2 further studies concurs with the findings of the meta-analysis. Meta-analysis of 10 studies showed a statistically significant difference in wound size reduction (MD: -3.39 cm2 (95% CI: -5.34 to 1.45; p = 0.0006), in favour of the insulin group, with a narrative analysis of 5 further studies, concurring with the findings of the meta-analysis. The certainty of the evidence is low or very low certainty evidence, as it was downgraded mainly for high or unclear risk of bias across multiple domains.
    CONCLUSIONS: Study findings show that topical insulin therapy may enhance wound healing in adults with DFUs. However, due to methodological limitations, inconsistent application of the intervention and outcome measures, yielding low or very low certainty evidence, definitive conclusions cannot be drawn. Therefore, further large, high-quality, multicentre trials are needed to validate the findings here.
    Keywords:  Diabetic foot ulcers; GRADE appraisal; Meta-analysis; Randomised controlled trial; Systematic review; Topical insulin therapy; Wound healing
    DOI:  https://doi.org/10.1016/j.jtv.2026.101032
  25. Biochem Biophys Res Commun. 2026 Jul 11. pii: S0006-291X(26)01032-6. [Epub ahead of print]830 154268
      Diabetic Foot Ulcers (DFUs) are a serious global health crisis, mainly because of persistent bacterial biofilm formation and the rise of Methicillin-Resistant Staphylococcus aureus (MRSA) infections. Current therapeutic strategies are less effective and fail to resolve the core challenges of multidrug resistance and defective tissue regeneration. These limitations require the development of multifunctional therapeutic systems. This review discusses a dual-action platform - Moringa based smart scaffolds. These scaffolds are designed to provide a targeted solution for MRSA infected DFUs. The therapeutic potential lies in Moringa oleifera's rich phytochemical profile, which demonstrates potent antimicrobial, antioxidant and pro-healing activities. This approach addresses key limitations of crude phytochemical formulations, including instability and poor bioavailability. The review highlights the strategic integration of these bioactives into poly(lactic-co-glycolic acid) (PLGA) nanoparticles. These nanoparticles are integrated into electrospun nanofibrous scaffolds, which not only provide an extracellular matrix (ECM) mimicking structure to support cell adhesion and angiogenesis but also enable controlled, sustained and stimuli-responsive release of the Moringa payload. The systems are engineered to respond to the acidic and ROS-rich microenvironment of chronic wounds. Combining phytochemicals with nanoparticle-based scaffold will improve infection control and wound repair in chronic DFUs.
    Keywords:  Diabetic foot ulcers; MRSA; Moringa oleifera; Reactive oxygen species; Smart scaffolds
    DOI:  https://doi.org/10.1016/j.bbrc.2026.154268
  26. Sci Prog. 2026 Jul-Sep;109(3):109(3): 368504261465748
      Diabetic foot ulcers (DFUs) are a major cause of morbidity and mortality in people with diabetes. Understanding differences in DFU burden and outcomes between T1DM and T2DM is important for advancing precision medicine. This narrative review summarizes evidence reporting DFU prevalence, healing, recurrence, infection, and lower extremity amputation outcomes separately in T1DM and T2DM. Population surveys suggest a higher lifetime prevalence in T1DM, driven by longer disease duration, whereas registry-based and database studies generally report higher annual incidence rates in T2DM, reflecting older age and macrovascular comorbidities. Crucially, most included studies lacked the multivariable adjustment and statistical power necessary to isolate diabetes type as an independent prognostic driver. Consequently, a lack of statistically significant differences should not be misinterpreted as proof of clinical equivalence. Overall, the available evidence suggests that time to healing does not differ substantially between individuals with T1DM and T2DM, though outcomes were primarily driven by local wound characteristics and vascular status. Recurrence is frequent and remains a clinical challenge irrespective of diabetes type, although people with T2DM may experience a greater burden. Evidence further indicates that the risk of LEAs is increased in both T1DM and T2DM, although the magnitude and comparative contribution of each diabetes type varies across populations and study designs, with real-world clinical cohorts indicating that advanced age and a neuro-ischemic phenotype in T2DM drive substantial post-ulcer morbidity. Finally, a higher relative risk of deep bone infections (osteomyelitis) emerges as one of the most severe diabetes-related foot infections and is associated with poor outcomes, with several reports suggesting a particularly pronounced burden among people with T1DM. Differences in DFU burden and outcomes between T1DM and T2DM appear to be driven more by patient phenotype than diabetes type itself. Precision-medicine approaches may help improve future prevention and management strategies.
    Keywords:  diabetic foot infection; diabetic foot ulcers; lower-extremity amputation; type 1 diabetes; type 2 diabetes; wound healing
    DOI:  https://doi.org/10.1177/00368504261465748
  27. JMIR Diabetes. 2026 Jul 13. 11 e84463
       Background: Wearable technologies, including smart insoles and sensor-equipped footwear, enable continuous monitoring of key foot parameters such as plantar pressure and temperature in individuals at risk of diabetic foot ulcers (DFUs).
    Objective: This systematic review aimed to evaluate the technological characteristics and clinical applications of wearable devices for monitoring DFU-related parameters.
    Methods: This review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Journal articles, theses, and dissertations evaluating wearable technologies for DFU prevention or monitoring were eligible if they involved human participants and were published in English or Persian. Studies focused on nonwearable or non-foot-based systems were excluded. A comprehensive search was conducted in PubMed, Embase, Web of Science, and Scopus from July 2024 to May 2025. Two reviewers (HE and SS) independently screened studies and extracted data. The methodological quality of included studies was assessed using the Mixed Methods Appraisal Tool (MMAT) 2018. Results were synthesized using descriptive synthesis.
    Results: A total of 1088 records were identified, of which 23 studies met the inclusion criteria. The included studies varied in design, sample size, and follow-up duration. Wearable devices included smart insoles, socks, and external sensors, primarily monitoring plantar pressure and temperature. Devices differed in sensor type, placement, number, communication protocols, and data acquisition rates. Participants typically had diabetes, and many had a history of neuropathy or prior DFUs.
    Conclusions: Wearable technologies show promise for monitoring DFU risk factors and supporting early detection. However, the evidence base is limited by heterogeneity in study designs, small sample sizes, and short follow-up periods. Further high-quality studies are required to evaluate their potential clinical benefits, long-term outcomes, and role in preventing DFUs and improving patient care.
    Keywords:  DFU prevention; Internet of things; diabetic foot ulcer; foot monitoring; smart insole; wearable technology
    DOI:  https://doi.org/10.2196/84463
  28. Ann Pharmacother. 2026 Jul 18. 10600280261462507
       OBJECTIVE: To review recently Food and Drug Administration (FDA)-approved antibiotics (2017-2026) for complicated and resistant urinary tract infections (UTIs), focusing on their pharmacology, spectrum of activity, clinical evidence, and potential role in the management of UTIs specifically in women.
    DATA SOURCES AND EXTRACTION: Information was obtained from FDA approval documents, prescribing information, pivotal clinical trials, and relevant peer-reviewed publications for antibiotics that were FDA-approved for UTIs between 2017 and 2026 using PubMed Central, MEDLINE, Scopus, and Web of Science databases. Data extracted included drug characteristics, approved indications, microbiological activity, efficacy and safety outcomes, and available evidence regarding use in women and special populations.
    DATA SYNTHESIS: Urinary tract infections are among the most common infections in women, with approximately 50% of all women experiencing at least one UTI in their lifetime. The efficacy of traditional therapies (trimethoprim/sulfamethoxazole, nitrofurantoin, and fluoroquinolones) has been limited by the rising prevalence of resistant pathogens such as extended-spectrum beta-lactamase. Gender-specific factors, including safety in pregnancy and lactation, effects on vaginal flora, are discussed. This article offers practical guidance on how pharmacists and health care providers play a crucial role in integrating new UTI antibiotics into practice, optimizing dosing, monitoring for adverse effects, and educating patients.Relevance to patient care and clinical practice in comparison with existing drugs:Provides an updated evaluation of recently FDA-approved antibiotics for UTIs in women, highlighting their enhanced stability against broad-spectrum beta-lactamases, improved safety profiles, and activity against multidrug-resistant pathogens. These new agents may expand treatment options beyond traditional first-line therapies such as nitrofurantoin and trimethoprim/sulfamethoxazole and support more effective outpatient management of complicated and recurrent UTIs. Practical considerations for integrating these newer agents into clinical practice are reviewed, with emphasis on the role of pharmacists within interprofessional health care teams and antimicrobial stewardship programs in optimizing the care of women with UTIs.
    CONCLUSION: Emerging antibiotics offer promising new treatment options for multidrug-resistant UTIs in women and may improve outcomes while supporting antimicrobial stewardship. However, additional research is needed to address evidence gaps related to effectiveness, safety, and long-term clinical use.
    Keywords:  antibiotic resistance; antibiotics; urinary tract infections; women’s health
    DOI:  https://doi.org/10.1177/10600280261462507
  29. bioRxiv. 2026 Jul 06. pii: 2026.07.01.735878. [Epub ahead of print]
       Aim: To investigate whether salivary immune cell profiling can serve as a non-invasive approach to monitor periodontal disease activity and therapeutic response by characterizing innate and adaptive immune cell dynamics in periodontitis.
    Materials and Methods: This longitudinal study included systemically healthy adults with periodontitis and healthy controls. Periodontal parameters (PPD, BOP, plaque/calculus, and radiographic bone loss) were recorded by calibrated examiners (κ=0.85) following established criteria. Stimulated saliva and gingival biopsies were collected before and 4-6 weeks after non-surgical periodontal therapy (NSPT), and from healthy controls. Multiparametric flow cytometry was used to characterize myeloid and lymphoid cell populations and polarization markers. Bacterial transcripts and host inflammatory markers were assessed by qRT-PCR. Statistical analyses were performed using one-way ANOVA.
    Results: Periodontitis subjects exhibited significantly elevated salivary bacterial transcripts, which decreased but did not normalize following NSPT. Both myeloid and lymphoid immune cell populations increased in periodontitis compared with healthy controls and declined after therapy. This was accompanied by a pronounced pro-inflammatory shift with elevated IFN-γ-producing macrophages, dendritic cells, Th1/Th17 cells, and B cells, including the novel identification of IFN-γ-producing B cells in saliva and mirrors the gingival immune cell profiles. In contrast, anti-inflammatory populations (IL-10-producing myeloid cells, Tr1 cells, and regulatory B cells) were reduced in disease and partially restored following NSPT.
    Conclusions: Salivary immunophenotyping non-invasively monitors PD activity and therapeutic response by capturing dynamic immune changes that reflect gingival signatures and track post-therapy resolution.
    Clinical Relevance: Scientific rationale: Salivary immune profiling offers a real-time, non-invasive tool for assessing periodontal disease status and treatment outcomes, with potential applications in precision diagnostics and personalized periodontal care.Principle findings: Periodontitis was associated with increased salivary bacterial burden and a marked pro-inflammatory immune profile involving both innate and adaptive immune cells, including newly identified IFN-γ-producing B cells. Non-surgical periodontal therapy partially restored anti-inflammatory immune responses and reduced inflammatory cell populations, supporting salivary immunophenotyping as a promising non-invasive biomarker approach for monitoring disease activity and treatment response.Practical implications: Salivary immune cell profiling could serve as a simple, non-invasive tool to monitor periodontal disease activity and response to therapy in clinical practice. Identification of specific inflammatory cell subsets may also aid in developing personalized diagnostic and therapeutic strategies for periodontitis.
    DOI:  https://doi.org/10.64898/2026.07.01.735878
  30. Front Med (Lausanne). 2026 ;13 1853536
       Introduction: Negative pressure wound therapy (NPWT) has been widely used in wound care, yet the optimal application mode-continuous, intermittent, or dynamic-remains unclear. This systematic review aimed to compare the effects of different NPWT modes on wound-healing-related outcomes and to provide evidence for mode selection in clinical practice.
    Methods: Following PRISMA guidelines, a systematic search was conducted across 11 databases-PubMed, MEDLINE, EMBASE, ProQuest, CINAHL, Web of Science, CENTRAL, CNKI, CBM, VIP, and WANFANG-from 1997 to 2024.
    Results: Ten clinical studies and 15 animal studies were included. Clinical studies involved both acute and chronic wounds, whereas animal studies mainly used full-thickness skin wound models. Reported outcomes included clinical efficacy, wound microenvironment, and molecular-level changes. Current evidence suggests that continuous, intermittent, and dynamic NPWT may influence wound healing in different ways. Compared with continuous NPWT, the two non-continuous modes-intermittent NPWT and dynamic NPWT-appeared to offer potential advantages in selected outcomes, particularly with respect to wound healing speed, tissue perfusion, and granulation-related responses.
    Discussion: Due to substantial heterogeneity in wound types, parameter settings, outcome measures, and study designs, the available evidence remains insufficient to establish a definitive ranking among NPWT modes or to determine optimal treatment parameters. Future research should focus on large-scale, high-quality, multicenter studies with refined wound-type stratification and greater standardization of pressure parameters and outcome measures to clarify the mode-specific effects, indications, and parameter settings of NPWT.
    Keywords:  negative pressure wound therapy; negative pressure wound therapy mode; systematic review; wound healing; wound management
    DOI:  https://doi.org/10.3389/fmed.2026.1853536
  31. mBio. 2026 Jul 13. e0073226
      Lytic enzymes encoded by bacteriophages are conventionally understood to serve a single function in the phage life cycle: to enable progeny release through host cell lysis. Here, we identify an unexpected dual functionality in LysB, a lytic cassette protein of mycobacteriophage D29, which exerts opposing effects on phage propagation depending on the stage of infection. In our model, during the early phase of phage expansion, LysB's activity is limited to infected cells, hydrolyzing their outer membrane to facilitate efficient virion release. However, as the infection progresses, LysB accumulates in the extracellular environment, eventually reaching levels sufficient to act on uninfected bystander cells, rendering them resistant to infection. Consistent with this model, deletion of lysB impairs progeny release at low multiplicity of infection yet enhances phage propagation at later stages of plaque expansion. We further show that exogenous treatment of host cells with LysB inhibits phage infection in a concentration-dependent manner, likely by removing cell-surface determinants required for phage adsorption. Together, these findings demonstrate LysB's ability to modulate infection dynamics at the population level, revealing a potential new mechanism for phage-encoded host resilience. Engineered phages that lack this self-limiting activity may offer a path toward more effective antibacterial agents for therapeutic applications.IMPORTANCELytic bacteriophages are often viewed as purely destructive viruses that rapidly eliminate their bacterial hosts. Yet, as in other predator-prey relationships, how these phages avoid exhausting their host populations remains poorly understood. Here, we report an example in which a phage-encoded protein that drives lysis also acts to limit it. LysB of mycobacteriophage D29 facilitates efficient virion release during infection but accumulates extracellularly as infection progresses, eventually blocking phage adsorption on uninfected cells in a concentration-dependent manner. The result is an intrinsic negative feedback on phage infection that might act to prevent host extinction. Given that rebounding infections pose a major challenge in the management of bacterial diseases, understanding and counteracting the mechanisms that underpin host resilience is crucial for the therapeutic application of phages.
    Keywords:  bacteriophage; endolysin; mycobacteria; phage therapy; tuberculosis
    DOI:  https://doi.org/10.1128/mbio.00732-26
  32. BMC Nurs. 2026 Jul 16.
       BACKGROUND: The increasing volume and complexity of orthopedic surgery have expanded the involvement of ward-based registered nurses in postoperative wound care. Although registered nurses receive foundational wound care education as part of their professional preparation, those without specialist wound care credentials may encounter challenges when managing complex orthopedic surgical wounds. Their experiences, role boundaries, and perceived support needs remain insufficiently explored. This study aimed to explore ward-based registered nurses' perceptions of their roles and professional boundaries in orthopedic surgical wound management and to identify perceived strategies for supporting their practice.
    METHODS: A descriptive qualitative study was conducted in an orthopedic ward of a tertiary hospital in China. Fourteen ward-based registered nurses were purposively recruited and participated in semi-structured interviews. Data were analysed using Braun and Clarke's thematic analysis approach.
    RESULTS: Four themes were identified: negotiating professional boundaries within clinical hierarchies, evolving role identity in orthopedic surgical wound care, developing professional capacity for safe and responsive wound management, and sustaining practice development through continuing education and organizational support. Participants described surgical wound care as an expanding but ambiguously defined area of nursing practice. Their accounts highlighted a mismatch between foundational wound care education and the demands of complex orthopedic surgical wounds, variability in physicians' treatment preferences and local ward routines, limited decision-making authority, and inconsistent interprofessional collaboration. Participants also emphasized the importance of timely nursing involvement, clinically relevant continuing education, standardized protocols, and clearer escalation pathways for supporting safe and coordinated wound care.
    CONCLUSIONS: Ward-based registered nurses without specialist wound care credentials make important contributions to orthopedic surgical wound management through ongoing assessment, timely dressing care, patient education, and communication with physicians and wound care specialists. However, their expanding role is shaped by unclear professional boundaries, variable local practices, limited authority in wound-related decision-making, and uneven access to continuing education. Clearer role delineation, standardized protocols, structured continuing education, and collaborative escalation pathways are needed to support safe and consistent wound care.
    Keywords:  Orthopedic nursing; Professional boundaries; Qualitative research; Registered nurses; Surgical wound care
    DOI:  https://doi.org/10.1186/s12912-026-05050-8
  33. Acta Diabetol. 2026 Jul 13.
    SID-AMD Diabetic Foot Study Group
      Diabetic foot is one of the most serious chronic complications of diabetes mellitus and reflects the systemic burden of the disease. Preventive strategies and structured management pathways are therefore essential elements of diabetes care. Lifetime occurrence of foot ulceration has been reported in nearly one-third of individuals with diabetes, and these lesions account for most non-traumatic lower-extremity amputations. Furthermore, the estimated five-year mortality following ulceration is 30%. This document aims to ensure an appropriate, multidisciplinary care pathway for patients with diabetic foot, tailored to clinical complexity and aligned with the different levels of care of Italian diabetes centers. The integrated model of diabetic foot care is based on the level of care that diabetes centers (local and hospital) can provide, including available personnel, expertise, and diagnostic and therapeutic resources to manage varying degrees of clinical complexity. Accordingly, three levels of care complexity, low, medium, and high, have been defined, with corresponding key diagnostic and therapeutic activities and healthcare professionals involved.
    Keywords:  Care pathways; Diabetic foot; Diabetology setting; Multidisciplinary care
    DOI:  https://doi.org/10.1007/s00592-026-02741-1
  34. Prog Mol Biol Transl Sci. 2026 ;pii: S1877-1173(26)00152-3. [Epub ahead of print]223 263-322
      Recent advances in biological specimen preparation, electron optics, and image processing software have led to explosive growth in structural biology, in particular, in bacteriophage structural studies in situ. Bacteriophages are microscopical organisms and represent the most populated biological system in the world. Here, we review the history of bacteriophage discovery, progress elucidating bacteriophage structure, the current state of the art, and the prospect for future development. We highlight their most essential structural details obtained by modern methods in structural biology. This knowledge could potentially increase the lethality of existing phages fighting bacterial infection, and facilitate creation of synthetic phages to carry drugs into bacteria that have become resistant to antibiotics.
    Keywords:  Baseplate; Capsid; Connector; Cryogenic electron microscopy; Neck; Phage; Portal; Structure; Tail fibers; Tail sheath; Tail spike; Tail tip; Tail tube
    DOI:  https://doi.org/10.1016/bs.pmbts.2026.06.010
  35. J R Soc N Z. 2026 Aug;56(4): e70064
      Evolution of drug-resistant mycobacterial infections warrants renewed efforts in identifying more efficient preventive and control strategies as well as alternative treatment options. Interest in phage therapy is regaining significant traction, especially in cases of failed conventional therapy. However, phage therapy faces challenges, including the identification of a suitable therapeutic phage, phage delivery, phage resistance, and host immunity. This article reviews existing clinical literature on the therapeutic use of mycobacteriophages as adjuncts to antibiotics in the treatment of drug-resistant mycobacterial infections and discusses such aspects as mycobacterial phage resistance, coevolutionary phage training, and impact of host immunity, as well as the benefits and limitations of phage therapy. To date, at least 27 patients received mycobacteriophage therapy, where M. abscessus accounts for 82.1% of all cases in contrast to M. chelonae (7.1%), M. avium complex (3.6%), and BCG (3.6%). Mycobacteriophages used were either wild-type or derivatives of BPs, D29, Fionnbharth, Fred313, Itos, Muddy, or ZoeJ. Evolution of phage resistance is rare, and the impact of host immunity varies between patients, with most treatment outcomes having little to do with immune responses. However, identification of a suitable therapeutic mycobacteriophage remains a pressing challenge, especially for infections involving the smooth morphotype of M. abscessus. Only about 10 mycobacteriophages made it to clinical use, including wild-type, host range mutants and engineered derivatives, which warrants the expansion of this narrow arsenal of therapeutic mycobacteriophages by building novel candidates or expanding the host ranges of existing ones. The outcomes recorded in these case reports represent a significant achievement. However, the results remain exploratory due to sample size limitations and therefore warrant larger, methodologically rigorous, controlled trials in the future.
    Keywords:  mycobacteria; mycobacterial infections; mycobacteriophage therapy; mycobacteriophages; nontuberculous mycobacteria
    DOI:  https://doi.org/10.1002/snz2.70064
  36. Acta Diabetol. 2026 Jul 14.
    SID-AMD Diabetic Foot Study Group
      Although scientific societies have made substantial efforts through the implementation of guidelines and by increasing awareness among both expert and non-expert healthcare professionals (HCPs), delayed referral of patients with diabetic foot ulcers (DFUs) to specialized diabetic foot services (DFS) remains a common issue. Early referral to a DFS has been widely documented as the most important intervention for achieving ulcer healing, reducing healing time, and avoiding major amputations. Furthermore, it has been reported that many HCPs working in primary care are not adequately trained in the recognition and management of DFUs. The onset of a DFU may rapidly deteriorate and evolve into a diabetic foot attack (DFA), a dangerous condition characterized by advanced ischaemia, severe infection, and/or acute Charcot neuroarthropathy, potentially leading to limb- and life-threatening consequences. The current document aims to identify the main clinical patterns of DFA, describing their clinical characteristics, appropriate management pathways, and indications for treatment. Accordingly, the authors aimed to develop a practical, fast-track model to define referral timing to specialized diabetic foot centers based on the severity of each clinical presentation. The proposed fast-track approach distinguishes between emergency conditions requiring immediate management within hours and urgent conditions requiring specialist evaluation within 24-48 h to prevent clinical deterioration and poorer outcomes.This document was developed on behalf of the Italian Diabetic Foot Study Group of Società Italiana di Diabetologia (SID) and Associazione Medici Diabetologi (AMD) with the aim of reducing cases of delayed referral and their severe consequences.
    Keywords:  Diabetic foot; Diabetic foot attack; Diabetic foot ulcers; Fast-track pathway; Limb salvage
    DOI:  https://doi.org/10.1007/s00592-026-02746-w
  37. Cell Rep. 2026 Jul 17. pii: S2211-1247(26)00769-2. [Epub ahead of print]45(7): 117691
      Bacteriophages face intense competition within bacterial populations. Although bacteria encode diverse anti-phage mechanisms, strategies protecting virions at the host surface remain poorly understood. Here, we develop a receptor-centered discovery approach that captures phage proteins bound to host receptors during infection. Applying this strategy to bacteriophage λ and its outer-membrane receptor LamB, we identify Lom as a phage-encoded outer membrane protein that binds LamB. Structural, biochemical, and functional analyses show that Lom occupies the same LamB surface recognized by the receptor-binding protein gpJ, thereby reducing phage adsorption through receptor occlusion. Ribosome profiling indicates that lom is strongly expressed during late lytic growth and is also expressed during lysogeny, consistent with a role in receptor-level superinfection exclusion. Foldseek analyses identify structurally related Lom-like proteins in diverse temperate phages, raising the possibility that receptor occlusion is a more widespread strategy. These findings establish a framework for discovering receptor-level phage competition mechanisms.
    Keywords:  CP: microbiology; LamB; Lom; anti-phage; bacteriophage λ; cryo-EM; membrane protein; superinfection exclusion
    DOI:  https://doi.org/10.1016/j.celrep.2026.117691
  38. Saudi Med J. 2026 Aug;47(8): 1255-1264
       Objective: To describe the landscape of healthcare-associated infections (HAI) and, in particular, to pay attention to the types of infection that are usually seen, the most common infectious agents involved and the effective prevention strategies.
    Methods: A detailed search was performed using Google and PubMed, and studies that exclusively addressed healthcare associated infections or their mitigation. Studies published since 2000 were included. Data from individual articles were extracted and categorized by study focus, type of infection, causes and contributing factors, and documented mitigation strategies. Editorials, reviews, case studies, meta-analyses, and systematic reviews were excluded.
    Results: The analysis showed that infections related to healthcare, particularly bloodstream infections, infections that occur in intensive care units, and surgical site infections, significantly burden healthcare systems. Bacterial pathogens, including drug-resistant strains, such as Staphylococcus aureus, were identified as the most prominent etiologic agents, as well as several viral pathogens. The findings also underlined the importance of strong surveillance systems and especially systems that take advantage of digital platforms to effectively monitor the trends of infection and antibiotic resistance.
    Conclusions: The review highlighted the serious need for effective monitoring systems, especially those that use digital platforms, to monitor trends of infection and antibiotic resistance. The study highlighted the importance of a multifaceted preventive approach that involves prophylactic and therapeutic measures, as well as strict adherence to the sterile technique in healthcare institutions.
    Keywords:  Healthcare-associated infections; Infection control; Infection prevention strategies; Medical device contamination; Multidrug-resistant pathogens; Nosocomial infections; Sterilization practices
    DOI:  https://doi.org/10.15537/1658-3175.8817
  39. Clin Infect Dis. 2026 Jul 15. pii: ciag439. [Epub ahead of print]
      We describe a case of a child with macrolide-resistant Mycobacterium abscessus who initially had clinical improvement on a dual β-lactam regimen but continued to have positive cultures. Suitable phages active against the bacterial strain were identified, administered both systemically and directly to the ear, and were associated with microbiological remission.
    Keywords:   Mycobacterium abscessus infection; bacteriophage; pediatric
    DOI:  https://doi.org/10.1093/cid/ciag439
  40. Cell Host Microbe. 2026 Jul 16. pii: S1931-3128(26)00276-3. [Epub ahead of print]
      Anti-bacteriophage systems such as restriction-modification and CRISPR-Cas have DNA substrate specificity mechanisms that enable the identification of invaders. How Gabija, a highly prevalent nuclease-helicase antiphage system, limits phage replication while executing self- vs. non-self-discrimination remains unknown. Here, we show that phage-encoded DNA end-binding proteins that antagonize host RecBCD sensitize phages to Gabija. When targeting a temperate lambda-like phage in Pseudomonas aeruginosa, Gabija prevents phage genome circularization and subsequent replication. DNA end-binding complexes, including a phage exonuclease and a single-stranded DNA (ssDNA)-annealing protein or GamMu dimers that prevent loading of the host repair complex RecBCD, are necessary and sufficient to license phage and plasmid sensitivity to Gabija. Mutant escape phages lacking these DNA end-binding proteins become protected from Gabija by RecBCD translocation activities. RecBCD activity on the bacterial genome, presumably whenever it is linearized, also prevents Gabija from targeting self-DNA. Therefore, we propose that Gabija antagonizes the circularization and replication of linear DNA devoid of RecBCD as a mechanism to identify and antagonize foreign invaders.
    Keywords:  DNA end-binding factors; DNA repair complexes; DNA sensing; DNA-targeting; Gabija; Pseudomonas aeruginosa; RecBCD; antiphage immunity; bacteriophage; escape phage; helicase; linear DNA; nuclease
    DOI:  https://doi.org/10.1016/j.chom.2026.06.016
  41. 3 Biotech. 2026 Aug;16(8): 323
      Periodontitis is a chronic inflammatory disease driven by dysbiosis of the oral microbiome and is associated with both oral and systemic complications. Key pathogens from the red and orange complexes, along with Chlamydia pneumoniae, contribute significantly to disease progression and related systemic disorders. In this study, emerging biotechnological approaches, including immunoinformatics-driven vaccine design, were employed to develop a multi-epitope vaccine candidate (MEVC) targeting these polymicrobial infections. The MEVC was constructed using 13 B-cell epitopes, 15 cytotoxic T lymphocyte (CTL) epitopes, and 14 helper T lymphocyte (HTL) epitopes identified through experimental evidence and computational prediction. Immunostimulatory linkers and cholera toxin subunit B were incorporated as an adjuvant to enhance immunogenicity. Molecular docking demonstrated strong binding affinities between T-cell epitopes and HLA alleles. Physicochemical analysis indicated that the MEVC is stable, soluble, and exhibits a favourable half-life across biological systems. The construct ws predicted to be antigenic, non-allergenic, and host-compatible. Population coverage analysis of the selected HLA alleles indicated broad global applicability. The tertiary structure of the MEVC was modelled, refined, and docked with TLR2. HADDOCK 2.4 server yielded a binding score of - 196.2 ± 0.0, while PRODIGY predicted a binding affinity of - 13.2 kcal/mol for the MEVC-TLR2 complex. Codon optimization and in silico cloning into the pET-28(+) vector confirmed suitability for expression in Escherichia coli. Molecular dynamics simulations indicated stability of the MEVC-TLR2 complex, while immune simulations predicted strong humoral and cellular responses with sustained IgG, IFN-γ, and IL-2 production upon injection of MEVC into the host. Overall, the MEVC represents a promising therapeutic candidate warranting further experimental validation.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-026-04958-x.
    Keywords:  Immunoinformatics; Molecular docking; Multi-epitope vaccine; Oral microbiome; Periodontal pathogens; Periodontitis
    DOI:  https://doi.org/10.1007/s13205-026-04958-x
  42. Sci Rep. 2026 Jul 13.
      Diabetic foot ulcers (DFUs) are a serious complication of diabetes, and accurate, timely classification is crucial for supporting clinical decision-making. However, many existing approaches struggle to adequately capture the multi-scale and spatially heterogeneous characteristics of DFU morphology, which often limits their ability to integrate fine grained tissue details with broader contextual patterns. To address these limitations, we propose the Multi-Scale Enhanced Graph-Transformer Network (MS-EGT-Net), which uses a dual-scale feature extraction framework to process both high-resolution and downsampled region-of-interest (ROI) patches with a shared backbone. This design maintains semantic consistency while simultaneously capturing microscopic textures and global wound structures. In addition, a selective token refinement mechanism prunes less informative regions based on attention weight analysis, thereby retaining diagnostically relevant areas and enriching them with contextual information. The model further incorporates an adaptive graph encoding strategy that combines semantic affinity with spatial proximity to represent histopathological relationships and local structural coherence, and a bidirectional cross-scale attention module that promotes reciprocal integration between local and global features to form a more comprehensive diagnostic representation. Experimental results demonstrate that MS-EGT-Net consistently outperforms state-of-the-art methods across multiple evaluation metrics, indicating that it provides an effective solution for DFU classification with strong potential for clinical application.
    Keywords:  Cross-attention fusion; Diabetic foot ulcer; Graph-transformer; Multi-scale extraction
    DOI:  https://doi.org/10.1038/s41598-026-60024-9
  43. Dent Med Probl. 2026 May-Jun;63(3):63(3): 607-615
       BACKGROUND: Chronic inflammation in the oral cavity has a negative effect on the course of chronic mucosal lesions.
    OBJECTIVES: The present study aimed to compare the volume and proportional presence of aggressive periodontal pathogens in patients with oral lichen planus (OLP) accompanied by desquamative gingivitis (DG) vs. those with OLP without gingival involvement. All patients in the cohort were also diagnosed with moderate chronic periodontitis. The observed differences may help explain the higher risk associated with gingival involvement in OLP.
    MATERIAL AND METHODS: The presence of periodontal pathogens was evaluated in 50 biopsy-confirmed OLP with DG cases and 50 OLP cases without gingival manifestations. All participants presented with chronic periodontitis of comparable severity (moderate: periodontal pocket depth (PPD) up to 6 mm). Aggressive periodontal pathogens were identified and quantified using DNA testing (VariOr®-Dento). The periodontal status was assessed using orthopantomography (OPG) or cone-beam computed tomography (CBCT), in combination with the clinical examination of periodontal pockets.
    RESULTS: In comparison with the non-gingival OLP cases, the OLP cases with gingival involvement exhibited a significantly higher proportional presence of aggressive periodontal pathogens (p = 0.0009) and a higher bacterial load (n/μL; p = 0.001). Desquamative gingivitis associated with OLP was also linked to an increased risk of subsequent periodontal resorption. Given the unstable chronic inflammatory environment, careful monitoring of periodontal tissues in OLP cases appears to be essential, as persistent inflammation may contribute to an elevated risk of malignant transformation.
    CONCLUSIONS: Our findings demonstrate a significant difference in the presence of aggressive periodontal pathogens between OLP cases with and without gingival involvement. The median pathogen volume in the OLP with DG cases was over 7.4 times higher. Chronic inflammation and bacterial by-products may act as cofactors in the development of dysplasia and the malignant transformation of oral lichen with dysplasia (OLD), which may present clinically as DG.
    Keywords:  DNA testing; desquamative gingivitis; oral lichen planus; oral potentially malignant disorder; periodontal pathogens
    DOI:  https://doi.org/10.17219/dmp/207667
  44. Adv Protein Chem Struct Biol. 2026 ;pii: S1876-1623(26)00038-6. [Epub ahead of print]153 437-454
      The therapeutic manipulation concerning towards wound healing meets the different macroscopic levels such as immunological mechanisms, molecular signalling networks, developmental biology (regeneration) and drug discovery. From the epidermal skin infection to the deprived wound conditions, they are turned around into either scar or regenerated tissues. The restoration of tissue networks meets an intrinsic and dynamic rewinding processes from gene signals to several enzymes secretion led healing actions. Several advancements made in the wound healing materials and therapeutic assistive kits. Nanoparticle got high significant potential does not allow the drug waste rather it enhance target specific modifiers that either increase or decrease inflammatory response depend on the acute and chronic condition. And, there intrinsic pathways and growth regulators where activated in the entire process of wound healing. This review, encompasses from the rudimentary process to mechanism of highly advanced.
    Keywords:  Growth factors; Inflammatory responses; Keratinocytes; Macrophages; TENG
    DOI:  https://doi.org/10.1016/bs.apcsb.2026.04.007
  45. BMJ Open. 2026 Jul 15. 16(7): e114068
       INTRODUCTION: Digital tools such as virtual reality, mobile applications and digital devices are being implemented across various healthcare practice settings. Engagement in occupations is central to occupational therapy, supporting health and quality of life. Occupational therapists support people with disabilities to participate in occupations by enhancing their abilities or adapting tasks and environments. However, literature rarely specifies how digital technologies are used by occupational therapists, with whom they are implemented, when and where they are delivered, what occupations are addressed or the enablers and barriers that influence the uptake of digital technologies in practice. This scoping review will map and synthesise the existing evidence on how occupational therapists use digital technologies to support people with disabilities to engage in occupations. By identifying the types of technologies used, their purposes, target populations and practice contexts, this review will inform the effective use of digital technologies by occupational therapists and their clients.
    METHODS AND ANALYSIS: This review will be conducted in accordance with the Joanna Briggs Institute methodological framework for scoping reviews and reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. To identify relevant evidence, we will search several electronic databases, including CINAHL Complete, MEDLINE, SPORTDiscus, Scopus, ERIC and OTseeker. Search limits will include full-text articles published in English from 2020 onwards. Title and abstract screening will be conducted independently by at least two reviewers against the inclusion and exclusion criteria followed by full-text review. Data extraction will use a structured form to capture key information such as study characteristics, types of digital technologies, country, participant information, occupation-based focus of intervention and reported outcomes. The extracted data will be analysed using both qualitative and quantitative approaches, with findings presented in tables, narrative summaries and other descriptive formats.
    ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review as it will synthesise evidence from existing literature. The review findings will be reported in peer-reviewed publications.
    TRIAL REGISTRATION NUMBER: https://osf.io/3dy9z.
    Keywords:  Artificial Intelligence; Digital Technology; Mobile Applications; Virtual Reality; Wearable Devices
    DOI:  https://doi.org/10.1136/bmjopen-2025-114068
  46. Int J Mol Sci. 2026 Jul 02. pii: 5955. [Epub ahead of print]27(13):
      Chronic wounds represent a growing global healthcare burden driven by persistent inflammation, polymicrobial biofilm formation, impaired tissue regeneration, and increased antimicrobial resistance. This review examines the mechanistic interplay between chronic wound pathophysiology, biofilm persistence, and antimicrobial peptide (AMP)-based therapeutics, with particular emphasis on translational barriers and advanced biomaterial-enabled delivery strategies. Current evidence demonstrates that AMPs exert multifactorial activities extending beyond direct antimicrobial effects, including membrane disruption, quorum-sensing inhibition, extracellular polymeric substance (EPS) destabilization, immune modulation, angiogenic stimulation, and promotion of re-epithelialization. However, their clinical translation remains limited due to proteolytic degradation, poor stability, cytotoxicity, rapid clearance, and inadequate retention within the hostile chronic wound microenvironment. To address these limitations, emerging biomaterial platforms-including hydrogels, electrospun nanofibers, nanoparticles, self-assembling peptide systems, and stimuli-responsive smart dressings-have been developed to improve AMP stability, controlled release, biofilm penetration, and regenerative efficacy. This review further highlights current preclinical and clinical challenges, including the lack of standardized polymicrobial biofilm models and translationally relevant wound systems, while discussing future perspectives such as artificial intelligence-assisted peptide design and precision wound therapeutics. We argue that peptide discovery is no longer the principal bottleneck: the rate-limiting steps are now peptide stabilization, biofilm-targeted delivery, and dosing, and no current platform yet couples validated eradication of mature polymicrobial biofilms with validated tissue regeneration in a clinically representative model. Collectively, AMP-enabled smart biomaterials may support the transition from passive wound management toward responsive, biofilm-targeted regenerative therapy.
    Keywords:  antibiofilm therapy; antimicrobial peptides; antimicrobial resistance; biofilm; chronic wound; peptide delivery systems; regenerative medicine; smart biomaterials; translational medicine; wound healing
    DOI:  https://doi.org/10.3390/ijms27135955
  47. Ocul Surf. 2026 Jul 15. pii: S1542-0124(26)00108-4. [Epub ahead of print]
      Infectious keratitis (IK, corneal infection) is a major contributor to blindness worldwide and can be caused by a diversity of pathogens including bacteria, fungi, viruses, and protozoa. Through numerous large scale epidemiology studies, common causative organisms have been identified within each group which has greatly informed current therapeutic approaches. However, diagnostic advancements in clinical microbiology have led to the increasing identification of rare, previously unrecognized causative agents, many of which pose clinical management challenges including delayed diagnoses and ineffective treatments. Moreover, as the epidemiology of IK shifts with time, emerging pathogens that once were rare, are increasing in incidence. This review synthesizes the current literature of rare (incidence of <3 patient cases/10 years, number of unique bacterial organisms = 26, number of unique fungal organisms = 42) and emerging (incidence ≥3/10 years, number of unique bacterial organisms = 9, number of unique fungal organisms = 10) bacterial and fungal pathogens associated with IK between 2015-2025. Global distribution, clinical risk factors, medical and surgical interventions and clinical outcomes are reported to provide further insight into how to more accurately diagnose and treat patients with this vision-threatening disease.
    Keywords:  Infectious keratitis; corneal ulcers; emerging pathogens
    DOI:  https://doi.org/10.1016/j.jtos.2026.07.007
  48. Front Digit Health. 2026 ;8 1774406
      Artificial Intelligence (AI) is transforming the pharmaceutical sector by optimizing care delivery and accelerating drug design. While AI introduces significant benefits, it presents complex challenges regarding intellectual property (IP) frameworks. This review examines AI-driven innovations in personalized medicine and drug design, with a specific focus on inventorship issues that directly affect pharmaceutical patent protection. We analyze recent United States (US) legal developments concerning AI inventorship, including the US Supreme Court's March 2026 denial of certiorari in Thaler v. Perlmutter, which definitively resolved the question of AI inventorship under US law, provide comparative analyses of approaches in Germany and China, and identify specific lessons, rather than wholesale reforms, that may help stakeholders navigate the evolving intersection of AI and pharmaceutical IP.
    Keywords:  artificial intelligence; copyright; drug discovery; intellectual property; international perspective; inventorship; patent law; personalized medicine
    DOI:  https://doi.org/10.3389/fdgth.2026.1774406
  49. Adv Neonatal Care. 2026 Jul 13.
       BACKGROUND: Neonatal respiratory outcomes remain leading drivers of neonatal intensive care unit (NICU) morbidity, mortality, and prolonged hospitalization, underscoring the need for accurate early risk prediction through artificial intelligence (AI) and machine learning (ML) approaches.
    PURPOSE: To conduct a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic review synthesizing AI/ML models predicting neonatal respiratory outcomes through a Life Course Health Development (LCHD) lens, examining whether models incorporate developmental timing, cumulative processes, and contextual factors.
    DATA SOURCES: PubMed, Embase, and Web of Science were searched from January 1, 2014, to July 18, 2025.
    STUDY SELECTION: Included peer-reviewed studies developing or validating AI/ML prediction models for neonatal respiratory outcomes with performance metrics. Excluded non-ML regression, non-original research, and non-English studies. Of 4319 records initially identified, 1780 unique records were screened, 33 underwent full-text review (0.76%); 16 met selection criteria (0.37%).
    DATA EXTRACTION: Two reviewers independently extracted study characteristics, inputs, algorithms, validation strategies, and performance metrics. Risk of bias was assessed using PROBAST + AI. Disagreements were resolved by consensus.
    RESULTS: Studies addressed bronchopulmonary dysplasia (n = 8), respiratory distress syndrome (n = 4), apnea of prematurity (n = 3), and massive pulmonary hemorrhage (n = 1). Discrimination was strong in internal validation (several models with an area under the receiver operating characteristic curve ≥0.85). External validation was rare (2/16); calibration reporting was sparse. No studies predicted postdischarge respiratory outcomes or included comprehensive determinants of health.
    IMPLICATIONS FOR PRACTICE AND RESEARCH: Although ML models show promise for NICU risk stratification, responsible clinical adoption requires multisite external validation, routine calibration, and nursing-informed designs incorporating development context. See Video Abstract, Supplemental Digital Content.
    Keywords:  apnea; artificial intelligence; bronchopulmonary dysplasia; life course health development; machine learning; neonatal intensive care unit; newborn; pulmonary hemorrhage; respiratory distress syndrome; respiratory outcome
    DOI:  https://doi.org/10.1097/ANC.0000000000001392
  50. J Clin Nurs. 2026 Jul 14.
       BACKGROUND: Intensive Care Units (ICUs) care for critically ill patients across all age groups, with many deaths occurring during or shortly after admission. For families, this can be associated with significant psychological distress, including prolonged grief, depression, and post-traumatic stress. Family experiences are influenced by the quality of end-of-life communication, involvement in decision-making, and the availability of bereavement support. Despite this, bereavement care across neonatal, paediatric, and adult ICUs remains inconsistent, highlighting the need for evidence-based strategies.
    OBJECTIVE: To identify, summarise, and report the effectiveness and impact of end-of-life and bereavement interventions delivered by ICU staff on family psychological, social, and physiological outcomes.
    DESIGN: Overview of reviews.
    SETTING(S): Neonatal, paediatric, and adult ICUs internationally.
    METHODS: A comprehensive search (PROSPERO CRD42024581827) was conducted across Medline, Embase, Scopus, CINAHL, Cochrane Database of Systematic Reviews, Web of Science, and PsycINFO, with an updated search in 2025. Screening was completed by two research team members. Risk of bias was assessed using ROBIS. Data were extracted as reported in each systematic review and analysed narratively.
    RESULTS: Fifteen systematic reviews (145 primary studies) were included across neonatal (n = 4), paediatric (n = 1), adult (n = 9), and mixed settings. Interventions were diverse and often multi-component. Communication-focused strategies that were timely, honest, and individualised were associated with improved family satisfaction and perceptions of care. Opportunities for family presence, shared decision-making, and relational nursing support were reported as central to understanding, acceptance, and adjustment. Memory making and bereavement follow-up were valued, though impacts on psychological outcomes varied. Evidence was limited by inconsistent outcome measures and minimal paediatric-specific reviews.
    CONCLUSIONS: ICU family-focused end-of-life and bereavement interventions can provide meaningful support, but effectiveness is difficult to determine due to inconsistent implementation and methodological variation. Findings highlight the importance of individualised and relational approaches, and suggest culturally responsive care may influence how interventions are experienced.
    Keywords:  bereavement; critical care; end of life; nursing; overview of reviews; patient and family‐centered care; umbrella review
    DOI:  https://doi.org/10.1111/jocn.70438
  51. Int J Mol Sci. 2026 Jul 05. pii: 6038. [Epub ahead of print]27(13):
      Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), remains a leading cause of skin and soft tissue infections (SSTIs) worldwide. Patients with renal edema, including those with nephrotic syndrome and chronic kidney disease (CKD), and critical illness, are particularly susceptible because of barrier dysfunction, immune impairment, and altered antimicrobial pharmacokinetics. This narrative review examines the mechanisms linking renal edema to increased susceptibility to cutaneous S. aureus infection and discusses their diagnostic and therapeutic implications. Three interconnected pathophysiological pathways appear central to this susceptibility: disruption of the cutaneous barrier, nephrotic and uremic immune dysfunction, and impaired lymphatic immune surveillance. These abnormalities facilitate bacterial colonization, and invasion, while S. aureus further exploits the renal host through adhesins, toxins, biofilm formation, and immune-evasion mechanisms. The review also highlights the challenges of managing severe staphylococcal infections in patients with kidney disease and critical illness, where augmented renal clearance, expanded volume of distribution, extracorporeal renal support, and fluctuating renal function may substantially influence antimicrobial exposure. Current management requires early recognition, source control, individualized antimicrobial selection, renal-adapted dosing, therapeutic drug monitoring, and antimicrobial stewardship. Although emerging anti-virulence and immunomodulatory strategies show promise, most remain at the preclinical or early translational stage. Overall, renal edema should be regarded as a biologically active modifier of host-pathogen interactions that contributes to increased susceptibility to cutaneous S. aureus infection across the spectrum of kidney disease.
    Keywords:  MRSA; Staphylococcus aureus; biofilm; chronic kidney disease; cutaneous infection; nephrotic syndrome; renal edema; skin and soft tissue infections; virulence factors
    DOI:  https://doi.org/10.3390/ijms27136038
  52. Med Chem Res. 2026 Apr 23.
      The identification of therapeutically actionable targets and the design of effective small-molecule modulators remain central challenges in drug discovery, particularly for complex diseases driven by dynamic, interconnected molecular networks. Recent advances in artificial intelligence (AI) and machine learning are reshaping this landscape by enabling integrative analysis of large-scale biological data, systematic navigation of chemical space, and data-driven optimization of molecular properties. In this review, we outline how AI transforms small-molecule drug discovery by linking target discovery, tractability assessment, and chemical design within integrated, experiment-informed workflows. We highlight AI-enabled strategies for target discovery that integrate network biology, multimodal data fusion, and perturbation-aware modeling. These approaches identify context-specific, functionally actionable targets, including non-enzymatic proteins, protein-protein interactions, and other historically challenging classes. We then focus on advances most relevant to medicinal chemistry, including structure and complex prediction, docking and affinity modeling, ligand-based learning, generative molecular design, ADMET prediction, and synthetic feasibility assessment. Finally, we discuss current limitations related to data quality, generalizability, interpretability, and experimental translation. We emphasize the critical future role of integrated, context-aware AI workflows that connect target discovery with chemical design and experimental feedback. Together, these advances position AI as a robust framework for accelerating the discovery of therapeutically relevant targets and small-molecule modulators.
    Keywords:  ADMET prediction; Artificial intelligence; machine learning; molecular design; target discovery
    DOI:  https://doi.org/10.1007/s00044-026-03562-1