bims-fagtap 2026-03-08 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2026–03–08
twenty-one papers selected by
Luca Bolliger, lxBio

Bacteriophage Therapy: Current Strategies and Future Perspectives.
Precision of a phage susceptibility spot assay assessed with 154 clinical Staphylococcus aureus isolates.
Phage isolation and functional characterization reveal strong antibiofilm activity against Pseudomonas aeruginosa in a cystic fibrosis sputum model.
Phage therapy for treatment of bacterial vaginosis.
Global strategies to fight carbapenem-resistant Acinetobacter baumannii (CRAB) infections.
Co-producing shared wound care education: experiences of service users and healthcare professionals.
Cystic fibrosis year in review 2025.
Pseudomonas aeruginosa Biofilms in Cystic Fibrosis: Interactions, Methods, and Therapeutic Strategies.
Microbiome dysbiosis and therapeutic restoration in atopic dermatitis.
The balance between defence systems and horizontal gene transfer shapes adaptation in clinical strains of Acinetobacter spp.
New concept in wound infection management: From bacterial eradication to microbiome modulation.
Lipopolysaccharide-targeting treatments for multidrug-resistant Pseudomonas aeruginosa.
The oral microbiome as a regulatory hub for systemic health: a systematic review of mechanistic links and clinical implications.
Development of a supportive-educative nursing model based on health promotion for independent wound care in diabetic foot ulcer patients: A cross-sectional study.
Unravelling the pathophysiology of diabetic foot ulcer: insights into a complex wound healing process.
Sulodexide for limb salvage in refractory diabetic foot ulcer with arteriosclerosis obliterans: a case report.
Dynamics of gut bacteriophage in diversity outbred mice studied over lifespan and during extreme caloric restriction.
Nature meets machine: the AI renaissance in natural product drug discovery.
The gut-lung axis in celiac disease: a narrative review of pulmonary manifestations and pathogenic mechanisms.
Isolation of Bacteriophages and Their Lytic Profile From River and Waste Water Samples in South Western Uganda.
Transcriptomics in Venous Leg Ulcers (VLU): A Systematic Review.

MedComm (2020). 2026 Mar;7(3): e70645

Bacteriophage Therapy: Current Strategies and Future Perspectives.

Zihe Zhou, Hanyu Fu, Mengzhe Li, Zhongyu Han, Zhenchao Wu, Huahao Fan, Ning Shen, Jiajia Zheng.

  Antimicrobial resistance represents a significant global health threat, demanding alternative treatments beyond traditional antibiotics. Phage therapy has resurged as a promising solution to address this challenge. This manuscript offers an in-depth examination of phage applications in clinical settings, encompassing the treatment of multidrug-resistant infections, prevention of hospital-acquired infections, and development of phage-based vaccines. Advanced strategies are explored, including phage-antibiotic synergy, biomaterial-enhanced delivery systems to improve phage stability, and the rational design of engineered phages to expand host range and optimize lytic efficacy. Additionally, the application of genetic engineering to broaden phage host ranges and convert temperate phages into lytic variants is discussed. In hospital infection prevention, phages demonstrate substantial potential, such as eliminating bacterial biofilms on medical devices, disinfecting environmental surfaces, and controlling waterborne pathogens in hospital water systems. Furthermore, phages offer a versatile platform for vaccine development, facilitating efficient antigen display and nucleic acid delivery. Despite progress, challenges persist in pharmacokinetics, standardized production, and regulatory approval. This review synthesizes recent preclinical and clinical developments, emphasizing the transformative potential of phage-based therapies while acknowledging the barriers to their clinical implementation.

Keywords:  antimicrobial resistance; hospital‐acquired infections; phage therapy; phage‐based vaccines; phage–antibiotic synergy

DOI:  https://doi.org/10.1002/mco2.70645
Microbiol Spectr. 2026 Mar 03. e0328425

Precision of a phage susceptibility spot assay assessed with 154 clinical Staphylococcus aureus isolates.

Sebastian C Herren, Christoph L Zink, Jay Mandrekar, Robin Patel.

  Lytic phages are a promising consideration to combat recalcitrant bacterial infections. To advance the possibility of using phage therapy in the clinical routine, standardized phage susceptibility testing methods are needed. Here, staphylococcal phage K was tested against 154 periprosthetic joint infection-associated Staphylococcus aureus isolates using a double overlay spot assay in technical and biological triplicates. Individual plaques were assessed using a morphology scoring system ranging from 0 (no plaques) to 4 (large, clear plaques), with scores ≥2 considered indicative of infectivity. Overall, 107 isolates exhibited scores ≥2. The intra-day and inter-day coefficients of variation were 0.9 and 2.5, respectively. Plaque-forming unit per milliliter (PFU/mL) titers correlated with morphology scores (Spearman's ρ = 0.8, P < 0.0001). The results suggest high precision of the described spot assay assessing S. aureus susceptibility to phage K.IMPORTANCEStandardized laboratory assays for assessing phage susceptibility are a prerequisite for clinical implementation of phage therapy. No assay has been denoted a reference standard. Criteria that can be used to assess assay precision and suitability for routine testing are intermediate precision and repeatability. Here, staphylococcal phage K was tested using the double overlay spot assay against 154 periprosthetic joint infection-associated Staphylococcus aureus isolates in technical and biological triplicates. In addition to measuring phage titers, plaque-forming units were assessed with a scoring system. Results indicate high intermediate precision and repeatability of the method described.

Keywords:  Methicillin-resistant Staphylococcus aureus (MRSA); phage K; phage susceptibility testing; phage therapy

DOI:  https://doi.org/10.1128/spectrum.03284-25
Front Cell Infect Microbiol. 2026 ;16 1753740

Phage isolation and functional characterization reveal strong antibiofilm activity against Pseudomonas aeruginosa in a cystic fibrosis sputum model.

Madeline Bowder, Hannah Kapoor, Steven J Carrell, Lia Danelishvili.

  Pseudomonas aeruginosa is an opportunistic pathogen that forms persistent biofilms in the lungs of cystic fibrosis and other chronic pulmonary disease patients, contributing to antibiotic tolerance, recurrent infection, and clinical decline. The rise of multidrug-resistant P. aeruginosa underscores the urgent need for alternative therapies. Bacteriophages (phages) offer a powerful therapeutic approach by directly lysing bacteria, diminishing biofilm structures, and overcoming mechanisms that limit antibiotic efficacy. In this study, a library of 61 distinct P. aeruginosa phages was isolated and screened against 64 clinical isolates, identifying eight with broad host range and high lytic activity. These phages, including PA-319, PA-575, and PA-711, effectively prevented P. aeruginosa colonization on A549 human lung epithelial cells, inhibited bacterial biofilm formation as well as compromised established biofilms, surpassing the effects of high-concentration antibiotics. Genomic and transmission electron microscopy analyses revealed functional heterogeneity, including nucleus-forming and non-nucleus-forming jumbo phages and depolymerase-encoding genes. Our phage library provides a valuable resource for advancing research, developing combinatorial phage therapies, and optimizing treatment strategies against chronic, drug-resistant P. aeruginosa infections.

Keywords:  A549 epithelial cells; Pseudomonas aeruginosa; biofilm; colonization; jumbo phages; lytic phages; phage therapy

DOI:  https://doi.org/10.3389/fcimb.2026.1753740
Arch Microbiol. 2026 Mar 03. pii: 233. [Epub ahead of print]208(5):

Phage therapy for treatment of bacterial vaginosis.

Sara Mazinani, Neda Arjmand, Zahra Sheikh, Soleimany Darany, Narjes Habibimoghadam, Nada Khairi Younis, Radhwan Abdul Kareem, Hayder Naji Sameer, Mohaned Adil, Asma Sanjari Pour.



Keywords:  Bacterial vaginosis; Chlamydia trachomatis; Female infertility; Gardnerella; Phage therapy

DOI:  https://doi.org/10.1007/s00203-026-04774-0
Microb Pathog. 2026 Feb 28. pii: S0882-4010(26)00138-5. [Epub ahead of print] 108412

Global strategies to fight carbapenem-resistant Acinetobacter baumannii (CRAB) infections.

Nilesh Makwana, Dilip D Karad, Dheeraj, Bipin Yadav, Chetna Saini, Corinne Mercier, Arun S Kharat.

  Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a formidable healthcare-associated pathogen, particularly in intensive care units, where it causes severe infections associated with prolonged hospitalization, limited treatment options, and high mortality. This review provides an integrated analysis of the global epidemiology of CRAB, the molecular mechanisms driving carbapenem resistance, and the increasing clinical significance of antibiotic hetero-resistance, which contributes to diagnostic failure and poor therapeutic outcomes. We highlight advances in diagnostic technologies, including whole-genome sequencing, digital PCR, and CRISPR-based platforms, which enable rapid identification of resistance determinants and detection of hetero-resistant subpopulations that are frequently overlooked by conventional susceptibility testing. Current treatment strategies are critically evaluated, with emphasis on optimized antibiotic combinations and emerging agents such as sulbactam-durlobactam and cefiderocol, alongside alternative approaches including bacteriophage therapy, antimicrobial peptidomimetics, and immune-modulating adjuncts. In parallel, the review underscores the importance of infection prevention and control measures, antimicrobial stewardship programs, and coordinated global surveillance initiatives in limiting CRAB transmission in high-burden healthcare settings. Collectively, the evidence indicates that effective control of CRAB infections requires a multidisciplinary, multimodal strategy integrating accurate diagnostics, sustainable therapeutic interventions, and robust public health policies to mitigate the escalating global impact of this priority pathogen.

Keywords:  Antimicrobial resistance (AMR); carbapenem-resistant Acinetobacter baumannii (CRAB); global health policies; hetero-resistance; peptidomimetics; phage therapy

DOI:  https://doi.org/10.1016/j.micpath.2026.108412
Int J Qual Stud Health Well-being. 2026 Dec 31. 21(1): 2637799

Co-producing shared wound care education: experiences of service users and healthcare professionals.

Joanna Blackburn.

   PURPOSE: Shared wound care promotes collaboration between patients and healthcare professionals (HCPs) to improve wound management outcomes and enhance patient autonomy. Educational resources to support shared wound care are typically developed without the direct involvement of service users or HCPs, limiting their relevance, accessibility, and impact in community practice. This study aimed to co-produce an educational resource to support shared wound care in community settings by integrating the perspectives of both service users and HCPs.
METHODS: A four-phase explanatory sequential mixed-methods design was employed involving an online survey, focus groups and semi-structured interviews to explore the experiences, needs and preferences of HCPs and service users. Semantic thematic analysis was used to analyse the data.
RESULTS: Both groups prioritised clear information in a leaflet format about wound infection, wound dressing changes and the normal wound healing process to facilitate involvement in shared care tasks. Co-designing the educational resource ensured it was both clinically and contextually relevant, reflecting the real-world experiences of patients and clinicians.
CONCLUSIONS: Co-producing educational resources enhances their accessibility and applicability and supports continued engagement from service users in their own care, providing a model for collaborative resource development that aligns with person-centred and self-management principles in community healthcare.
PATIENT OR PUBLIC CONTRIBUTION: Service users with lived experience were involved in the conduct of this study.

Keywords:  Co-production; community nursing; patient education; person-centred care; qualitative research; shared wound care; thematic analysis

DOI:  https://doi.org/10.1080/17482631.2026.2637799
J Cyst Fibros. 2026 Mar 03. pii: S1569-1993(26)00040-8. [Epub ahead of print]

Cystic fibrosis year in review 2025.

Sophia T Pallenberg, Ester Zamarrón de Lucas, Andrea Párniczky, Raquel Lopes de Bragança.

  Cystic fibrosis (CF) is being reshaped by CFTR modulators (CFTRm), yet infection, inflammation, and multisystem comorbidities persist. This review of the 2025 CF literature summarizes how CF is evolving into a chronic, heterogeneous condition in the modulator era. First, we discuss the consolidation of elexacaftor/tezacaftor/ivacaftor (ETI) and next-generation modulators, highlighting durable gains in lung function and survival alongside persistent gaps in eligibility, access, and long-term safety, particularly for individuals with advanced structural lung damage or class I variants. Second, emerging mutation-agnostic therapy strategies are outlined, including ENaC blockade, neutrophil-directed anti-inflammatories like brensocatib, and gene and nucleic acid-based therapeutic approaches . Third, we examine airway infection and inflammation: while ETI reduces pathogen detection and systemic inflammatory markers, chronic Pseudomonas aeruginosa and heterogeneous neutrophilic endotypes frequently persist, and mucosal immune defects remain incompletely corrected. In this context, bacteriophage therapy has emerged as a candidate for multidrug-resistant infections, while microbiome-focused interventions show limited clinical impact despite clear shifts in microbial communities. Finally, as survival improves, pregnancy, age-related malignancy, and cardiovascular disease are becoming increasingly relevant, necessitating new models of multidisciplinary, lifespan care. Collectively, these developments mark a shift towards equitable, lifelong, system-level management of health in an aging and increasingly diverse CF population.

Keywords:  CFTR modulators; Cystic fibrosis; ENaC; Elexacaftor-tezacaftor-ivacaftor

DOI:  https://doi.org/10.1016/j.jcf.2026.02.010
Biomed Res Int. 2026 ;2026 5328382

Pseudomonas aeruginosa Biofilms in Cystic Fibrosis: Interactions, Methods, and Therapeutic Strategies.

Luis Ángel Núñez-García, Carlos Córdova-Fletes, María Carmen Barboza-Cerda, Elvira Garza-González.

This review explores the role of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) pathogenesis. Biofilms, the main bacterial lifestyle in CF lungs, are key in therapy failure, immune evasion, and chronic infection persistence. This review examines biofilm structure, emphasizing extracellular polymeric substances (Psl, Pel, alginate, eDNA) and their roles in structural stability, resistance to antibiotics, and immune modulation. Regulatory mechanisms, including c-di-GMP signaling and quorum-sensing systems, are detailed as key drivers of biofilm formation and maintenance. The review also highlights polymicrobial interactions, particularly with Staphylococcus aureus, Candida spp., and Aspergillus spp., and commensal bacteria, illustrating how interaction dynamics shape microbial behavior, virulence, and treatment outcomes. Methods for studying biofilms in CF-like conditions, such as advanced in vitro models and transcriptomic analyses, are outlined for their relevance in replicating the complex lung environment. Emerging antibiofilm strategies, including matrix-disrupting enzymes, quorum-sensing inhibitors, bacteriophage therapies, and nanomedicine, are discussed as promising tools to combat biofilm resilience. The review underscores the need for innovative therapeutic approaches and a deeper understanding of microbial and host interactions to improve clinical outcomes in CF patients.

DOI: https://doi.org/10.1155/bmri/5328382
Front Cell Infect Microbiol. 2026 ;16 1693905

Microbiome dysbiosis and therapeutic restoration in atopic dermatitis.

Ling Zhong, Xiyuan Zhou, Jia Su, Yue Zhang, Dingding Zhang, Huiying Wan.

  Atopic dermatitis (AD) is increasingly recognized as a chronic inflammatory skin disease driven by a self-reinforcing vicious cycle involving skin barrier dysfunction, immune dysregulation, and cutaneous microbiome dysbiosis. A hallmark of this dysbiosis is the overrepresentation of pathogens like Staphylococcus aureus and Malassezia species, alongside a marked loss of microbial diversity, particularly during disease flares. This review systematically dissects the host-derived factors-such as altered lipid profiles, reduced antimicrobial peptides, and elevated skin pH-that facilitate S. aureus colonization. We further examine how bacterial virulence factors amplify type 2 inflammation and impair barrier integrity, thereby sustaining the pathological loop. We also explore the emerging roles of the skin virome, particularly the phageome, and discuss how microbiome-targeted interventions, including bacteriotherapy with commensal bacteria and precision phage therapy, offer promising avenues for ecological restoration. Finally, we argue that future research must leverage multi-omics to understand strain-specific functions, ultimately guiding the development of personalized microbiome interventions for AD.

Keywords:  Cutaneous Malassezia; Staphylococcus aureus; atopic dermatitis; bacteriotherapy; microbiome

DOI:  https://doi.org/10.3389/fcimb.2026.1693905
J Appl Microbiol. 2026 Mar 06. pii: lxag069. [Epub ahead of print]

The balance between defence systems and horizontal gene transfer shapes adaptation in clinical strains of Acinetobacter spp.

Vigneshwaran Muthuraman, Proyash Roy, Paul Dean, Bruno Silvester Lopes, Saadlee Shehreen.

   AIM: Bacteria experience various selective pressures from the environment, including exposure to antibiotics and bacteriophages, which shape their defence strategies and horizontal gene transfer (HGT) dynamics. The relationship between defence system repertoires and HGT in clinically relevant Acinetobacter species remains poorly understood, limiting our ability to predict resistance evolution and design targeted phage therapies.
METHODS AND RESULTS: We analysed 132 genomes from 18 Acinetobacter species, focusing on the interplay between defence architectures and HGT markers. Our results reveal that defence repertoires differed across lineages. Most Acinetobacter spp. harbour multiple defence systems, whereas the clinically dominant A. baumannii international clone 2 (IC2) carried fewer but was strongly enriched for the phosphorothioation-based SspBCDE system and had very few restriction-modification systems. Strikingly, many defence systems were rarely found together. Defence genes were frequently associated with the presence of mobile elements, antibiotics, and heavy metal resistance. Plasmid-borne defence systems, especially BREX, were prevalent, highlighting the role of mobile elements in distributing both anti-phage defence and clinically relevant resistance traits.
CONCLUSION: Our results indicate that clinical success in A. baumannii is associated with a niche-driven defence profile and extensive linkage between defence genes, mobile elements, and resistance loci which are likely to influence both HGT-mediated resistance acquisition and phage susceptibility.

Keywords:  antimicrobial resistance; defence systems; phage therapy

DOI:  https://doi.org/10.1093/jambio/lxag069
APL Bioeng. 2026 Mar;10(1): 010901

New concept in wound infection management: From bacterial eradication to microbiome modulation.

Tingting Hu, Zihan Chen, Zhe Yin, Luling Zhou, Qin Chen, Yanting Han, Ka Li.

Wound infection represents a significant challenge in clinical practice. Traditional wound management, targeting sterility and relying on strategies of broad-spectrum bactericidal activity and antibiotic dependence, achieves partial infection control but induces severe complications, including exacerbated bacterial resistance and skin microbiota dysbiosis. With the continuous advancement of microbiome research, a novel consensus has emerged: the key to wound healing lies not in the complete eradication of all microorganisms but in maintaining the dynamic balance of the microbial ecosystem. This review aims to elaborate on the paradigm shift from "bactericidal eradication" to "microbial modulation" in wound care, analyze the inherent limitations of conventional antibacterial strategies, and systematically summarize the critical roles of skin commensal microbiota in promoting wound healing through core mechanisms such as competitive inhibition, metabolic regulation, and immune modulation. Furthermore, it proposes that the core strategy of future wound care should focus on precision microbial modulation and discusses the application prospects of cutting-edge technologies, including probiotics, postbiotics, and individualized precision interventions. The innovative significance of this paradigm in wound dressing design is envisaged, emphasizing the development of novel materials integrating microbiota-specific regulatory capabilities and smart responsive functions. This work provides theoretical support for the precision prevention and control of wound infections, the improvement of healing quality, and technological innovation in the field of wound care.

DOI: https://doi.org/10.1063/5.0314581
Expert Opin Ther Targets. 2026 Mar 05. 1-9

Lipopolysaccharide-targeting treatments for multidrug-resistant Pseudomonas aeruginosa.

Meggie Wang, Natalia V Kirienko.

   INTRODUCTION: Pseudomonas aeruginosa is an opportunistic, nosocomial, Gram-negative pathogen implicated in a wide variety of infection types and is especially problematic in chronic lung infections for patients with cystic fibrosis. Resistance to current antibiotics is frequent and rising, posing a serious public health threat, so development of new treatments is urgent.
AREAS COVERED: This review aims to describe the current variety of LPS-targeting anti-Pseudomonals, including antimicrobials, bacteriophages, and pyocins, and how research is working to combat the rise of multi-drug resistant (MDR) P. aeruginosa infections.
EXPERT OPINION: Pyocins, bacteriocins produced by P. aeruginosa, are an attractive potential treatment for MDR infections. Their high species-specificity, effective bactericidal activity, and relative stability and safety give them a promising treatment profile. It is likely that pyocin treatments could enter clinical testing, offering another lifeline for the future of combating P. aeruginosa.

Keywords:  Antimicrobials; Pseudomonas aeruginosa; lipopolysaccharide; multi-drug resistance; phage therapy; pyocins

DOI:  https://doi.org/10.1080/14728222.2026.2639679
J Oral Microbiol. 2026 ;18(1): 2635233

The oral microbiome as a regulatory hub for systemic health: a systematic review of mechanistic links and clinical implications.

Zhu Ling Guo, Ming Wang Cui, Yu Lei Dong, Shuai Wang.

   Background: The human oral microbiome is a highly diverse ecosystem with important roles in oral and systemic health. Beyond dental caries and periodontitis, oral dysbiosis has been increasingly implicated in the development of multiple non-communicable diseases.
Objective: To systematically synthesize evidence on the mechanisms linking oral dysbiosis to systemic diseases and to summarize its diagnostic and therapeutic implications.
Design: A systematic review was performed using major electronic databases. We screened 1,128 records and included 104 studies that met predefined eligibility criteria.
Results: Evidence indicates that oral dysbiosis may influence systemic health through several mechanisms, including hematogenous dissemination of oral pathogens and virulence factors (e.g. lipopolysaccharide), chronic systemic inflammation, molecular mimicry in autoimmune disorders, and microbial metabolic byproducts. The reviewed studies support associations between oral microbiome alterations and atherosclerotic cardiovascular disease, type 2 diabetes, Alzheimer's disease, rheumatoid arthritis, and gastrointestinal cancers. The literature also highlights the promise of non-invasive oral microbiome-based biomarkers for early detection and disease monitoring. Emerging microbiome-modulating interventions, including probiotics, prebiotics, and bacteriophage therapy, show potential for restoring oral eubiosis and improving systemic outcomes.
Conclusions: Oral dysbiosis is an important regulator of systemic disease processes and a promising target for diagnosis, prevention, and therapy. Integrating oral health and oral microbiome assessment into broader disease management may improve outcomes, although methodological standardization and stronger causal evidence are still needed.

Keywords:  Oral microbiome; inflammation; oral dysbiosis; oral-systemic link; systemic disease

DOI:  https://doi.org/10.1080/20002297.2026.2635233
Int J Nurs Stud Adv. 2026 Jun;10 100504

Development of a supportive-educative nursing model based on health promotion for independent wound care in diabetic foot ulcer patients: A cross-sectional study.

Novita Verayanti Manalu, Esti Yunitasari, Sriyono Sriyono, Nursalam Nursalam, Ferry Efendi, Yunus Elon.

   Background: Diabetic foot ulcers are a chronic complications of diabetes associated with substantial morbidity, amputation risk, and reduced quality of life. Promoting the patients' capacity for independent wound care is a key component of long-term management. Although health promotion and supportive-educative nursing approaches are widely advocated in nursing, empirically informed models specifically addressing independent wound care in diabetic foot ulcer patients remain limited, particularly in low-income and middle-income countries.
Objective: To develop a supportive-educative nursing model based on health promotion for independent wound care in patients with diabetic foot ulcers.
Design: A cross-sectional study was conducted during the model development phases.
Settings: Twenty-two community health centers in Bandar Lampung, Indonesia.
Participants: A total of 130 patients with grade 1-2 diabetic foot ulcers were recruited using purposive sampling, based on predefined inclusion and exclusion criteria.
Methods: This study represents the development phase of this model. Quantitative data were collected using validated questionnaires assessing individual factors, support and facilities factors, nursing factors, supportive-educative nursing, patient commitment, and independent wound care behaviors. Structural equation modeling using partial least squares was applied to examine associations among constructs and inform model development.
Results: Individual (β = 0.399, p = 0.002), support and facilities (β = 0.227, p = 0.022), and nurse (β = 0.296, p < 0.001) factors were significantly associated with supportive-educative nursing. Supportive-educative nursing was strongly associated with patient commitment (β = 0.724, p < 0.001), which in turn was associated with independent wound care behaviors (β = 0.486, p < 0.001). Direct associations between support and facilities and nurse factors and independent wound care were not significant, consistent with an indirect pathway through supportive-educative nursing and patient commitment.
Conclusions: This study proposes a health promotion-based supportive-educative nursing model in which patient commitment functions as a key mediating pathway linking nursing support to independent wound care. These findings provide an empirically informed framework to guide nursing practice and support future longitudinal and interventional research.
Registration: The Health Research Ethics Committee of Universitas Airlangga (Ref. No. 3664-KEPK), Investment and One-Stop Integrated Services Agency (Reference number 1871/070/06354/SKP/III.16/II/2025), and Bandar Lampung City Health Agency (Reference number B/400.7.22/III.02.V/02/2025).

Keywords:  Community health nursing; Diabetic foot ulcers; Health promotion; Nursing models; Self-care; Wound care

DOI:  https://doi.org/10.1016/j.ijnsa.2026.100504
Front Clin Diabetes Healthc. 2026 ;7 1759605

Unravelling the pathophysiology of diabetic foot ulcer: insights into a complex wound healing process.

Mohannad N AbuHaweeleh, Sara Ali, Yasmin Elsalakawi, Aisha Al-Khulaifi, Viviana Maggio, Manfredi Rizzo, Ammar Boudaka.

  Diabetic foot ulcer (DFU) is a common and debilitating complication of diabetes mellitus, representing a significant clinical challenge. This article delves into the intricate pathophysiology underlying DFU, aiming to enhance our understanding of this complex wound healing process. We explore the interplay of multifactorial aspects, including peripheral neuropathy, vascular insufficiency, and impaired immune response, which contribute to the development and progression of DFU. Moreover, the dysregulation of key cellular and molecular mechanisms involved in inflammation, angiogenesis, extracellular matrix remodeling, and infection are examined. A comprehensive understanding of the pathophysiology of DFU including oxidative stress, neuropathy, dysregulated angiogenesis, impaired immune response, and key molecular pathways supports the development of targeted therapeutic strategies beyond current treatments to improve wound healing, reduce complications, and enhance patient quality of care.

Keywords:  diabetes mellitus; foot ulcer; neuropathy; vascular insufficiency; wound healing

DOI:  https://doi.org/10.3389/fcdhc.2026.1759605
Front Endocrinol (Lausanne). 2026 ;17 1756228

Sulodexide for limb salvage in refractory diabetic foot ulcer with arteriosclerosis obliterans: a case report.

Zhaoyan Chen, Wei Lin.

   Background: Patients with diabetic foot ulcers (DFU) remain at substantial risk for impaired wound healing, even following successful revascularization. This clinical challenge is often associated with underlying microcirculatory dysfunction, highlighting a critical unmet need for effective intervention strategies.
Case description: A 77-year-old female patient was suffering from severe DFU on her right foot, with infected wound, complicated by arteriosclerosis obliterans of the lower limbs. She underwent surgical debridement and angiographically and hemodynamically successful endovascular angioplasty. Despite these interventions and restored macrovascular perfusion, the wound exhibited continuously deterioration, and the patient was at imminent risk of minor amputation. Therefore, persistent microcirculatory dysfunction was considered a major contributing factor to the poor healing response, prompting the initiation of a salvage regimen with intravenous Sulodexide (600 LSU/day). Following a 51-day Sulodexide treatment, complete wound healing was achieved and the patient was discharged.
Conclusion: This case report suggests that highly selected DFU patients unresponsive to standard therapies including successful revascularization, Sulodexide may be a plausible salvage or adjunctive therapeutic option. This observation is strictly hypothesis-generating and its potential role warrants investigation in future prospective clinical trials.

Keywords:  diabetic foot ulcer; limb salvage; microcirculation; peripheral arterial disease; sulodexide

DOI:  https://doi.org/10.3389/fendo.2026.1756228
Microbiome. 2026 Mar 03.

Dynamics of gut bacteriophage in diversity outbred mice studied over lifespan and during extreme caloric restriction.

Carter Merenstein, Lev Litichevskiy, Christoph Thaiss, Ronald G Collman, Frederic D Bushman.

   BACKGROUND: The majority of bacteria in the vertebrate gut harbor integrated bacterial viruses ("bacteriophages" or "phages"; integrated phage are termed "prophages"). To probe phage replication strategies in the mammalian gut microbiome, we investigated phage activity in a large longitudinal study of diversity outbred mice (913 animals) undergoing extreme dietary restriction with detailed phenotypic characterization across lifespan.
RESULTS: We assembled 54,119 candidate DNA viral genomes from 2997 longitudinal metagenomes, forming 6462 viral operational taxonomic units (vOTUs). Over 85% of vOTUs annotated as novel. Viruses annotated predominantly as prophages in the Caudoviricetes class. We detected no eukaryotic DNA viruses, and none of the strictly lytic Crassvirales order that is abundant in human gut. The most prevalent phages had the widest predicted host ranges. The relative abundance of most phages was highly correlated to that of their inferred host bacteria, suggesting quiescent prophages dominate viral metagenomes, consistent with "piggyback-the-winner" dynamics. After accounting for close phage-bacterial covariation, we did identify a subset of phages changing in relative abundance and prevalence relative to their hosts in response to dietary restriction and aging. In particular, phages with larger genomes become less common in diets with restricted calories, potentially reflecting a higher fitness cost to their host. Generalist phages were enriched for a gene encoding a single-strand DNA binding protein which is reportedly involved in DNA repair and protection from nucleases encoded by host cells. Lytic phages became more common with aging, and we observed a reduction in phage richness with age, both findings previously observed in human cohorts.
CONCLUSION: These studies enrich our understanding of DNA phage dynamics in gut while emphasizing the predominance of "piggyback-the-winner" strategies.

Keywords:  Bacteriophage; Metagenomic sequencing; Mouse; Virome

DOI:  https://doi.org/10.1186/s40168-026-02362-4
Nat Prod Bioprospect. 2026 Mar 02. pii: 37. [Epub ahead of print]16(1):

Nature meets machine: the AI renaissance in natural product drug discovery.

Rajesh Muthuraj, Jaikanth Chandrasekaran.

  Natural products (NPs) have long served as a cornerstone of drug discovery, yielding landmark therapeutics such as paclitaxel and artemisinin and providing sustained access to biologically relevant chemical space. Despite this legacy, NP-based discovery has gradually declined with the rise of synthetic chemistry and high-throughput screening, even as many contemporary "synthetic" drugs remain structurally inspired by natural scaffolds. Classical NP workflows-centered on phenotypic screening and bioassay-guided fractionation-continue to face persistent bottlenecks, including structural complexity, low bioactive yield, frequent rediscovery, and limited scalability. Rather than competing with NP research, artificial intelligence (AI) offers a complementary methodological framework to address these longstanding challenges. This review critically examines the bottlenecks inherent to traditional NP discovery and outlines how AI can be systematically integrated across the pipeline. We discuss AI-enabled advances ranging from natural language processing for mining ethnopharmacological knowledge to machine learning-driven dereplication, cheminformatics, and genome mining, with platforms such as GNPS2 exemplifying scalable progress. Case studies in antibiotic and anticancer discovery, as well as the modernization of traditional medicine, illustrate how AI-NP integration can accelerate early-stage discovery while enhancing translational relevance. Looking ahead, we examine emerging paradigms-including quantum machine learning, federated data ecosystems, and AI-assisted molecular design-that may further expand the scope of NP-based research. Collectively, this review presents a forward-looking framework in which AI functions not as a replacement for NP science, but as a synergistic discipline that enables more efficient, scalable, and informed exploration of nature-derived chemical diversity.

Keywords:  Artificial intelligence (AI); Cheminformatics; Dereplication; Drug discovery; Ethnopharmacology; Machine learning; Natural products (NPs); Traditional medicine

DOI:  https://doi.org/10.1007/s13659-025-00589-6
Gastroenterol Hepatol Bed Bench. 2025 ;18(4): 413-417

The gut-lung axis in celiac disease: a narrative review of pulmonary manifestations and pathogenic mechanisms.

Ahmed A Abdelmoaty, Maha E Alsadik, Khaled A Abdel-Sater.

   Aim: This narrative review synthesizes current evidence on the association between Celiac disease (CD) and pulmonary disorders, explores underlying mechanisms, and highlights clinical implications and future research directions.
Background: CD is a chronic autoimmune enteropathy triggered by gluten ingestion in genetically predisposed individuals. Although it primarily affects the small intestine, emerging evidence implicates extraintestinal involvement, particularly of the respiratory system, suggesting a potential gut-lung axis.
Methods: This narrative review was conducted using PubMed, Scopus, and Web of Science, covering literature published in English up to October 2025. Search terms combined 'celiac disease' OR 'coeliac disease' with ('lung disease' OR 'pulmonary' OR 'respiratory tract' OR 'asthma' OR 'bronchiectasis' OR 'COPD' OR 'interstitial lung disease' OR 'pulmonary hemosiderosis'). Inclusion criteria were peer-reviewed human studies reporting pulmonary manifestations in celiac disease. Exclusion criteria included non-English language, in vitro or animal studies, abstracts without full text, and insufficient clinical or mechanistic data. This was not a systematic review, and therefore no PRISMA flow diagram was generated."
Results: Large-scale registry studies in Scandinavia and case-based evidence across Europe and Asia support a spectrum of pulmonary manifestations in celiac disease, ranging from asthma and chronic cough to rare but life-threatening idiopathic pulmonary hemosiderosis. Asthma and chronic cough were the most commonly observed associations, with population-based studies reporting an elevated risk. Case reports and small cohorts described co-occurrence with bronchiectasis and interstitial lung disease, while rare cases confirmed links to idiopathic pulmonary hemosiderosis (Lane-Hamilton syndrome). Proposed mechanisms include systemic immune activation, increased intestinal and pulmonary permeability, micronutrient deficiencies, IgA deficiency, and chronic inflammation. Notably, several studies reported symptom improvement or resolution following a gluten-free diet (GFD).
Conclusion: Pulmonary manifestations of CD, though relatively uncommon, are clinically significant and often reversible with dietary intervention. Greater awareness, early recognition, and mechanistic research are essential to optimize patient outcomes.

Keywords:  Bronchiectasis; Celiac disease; Gut–lung axis; Interstitial lung disease; Pulmonary hemosiderosis

DOI:  https://doi.org/10.22037/ghfbb.v18i4.3229
Cureus. 2026 Jan;18(1): e102524

Isolation of Bacteriophages and Their Lytic Profile From River and Waste Water Samples in South Western Uganda.

Judith Owokuhaisa, Keneth Junior Male, Richard Ezinga, Edgar Mulogo, Moses Ntaro, Moses Mpeirwe, Joel Bazira.

  Background Bacteriophages are found almost everywhere in the environment, such as water, soil, and air, among others. They are effective against a wide range of pathogens because they are highly specific. This study aimed to identify phages from river and wastewater samples in south-western Uganda and determine their lysis profile against selected clinical bacterial isolates. Materials and methods Four different locations (Mbarara city and Ntungamo, Kabale, and Kisoro districts) in south-western Uganda were chosen for the collection of river and wastewater for isolation of potential phages. The culture and double agar overlay method was used to detect the lytic bacteriophages. Isolated phages were purified after diluting them in saline magnesium (SM) buffer, then centrifuged at 3,000 rpm for 10 minutes, and filtered through a 0.22 um syringe filter. After purification, the filtrate was used to determine the phage lytic activity, host range activity (using the spot method), and thermal stability (using the double agar overlay method). Results A total of 17 phages were isolated using Escherichia coli WG5 as the host. The phage concentration ranged from 5.5 x 106 -7.6 x 1011 pfu/mL. All the isolated phages were used for host range determination on Salmonella spp., Morganelli morganii, extended-spectrum beta-lactamase (ESBL) E. coli, Proteus mirabilis, Citrobacter freundii, Coryne bacteria spp., and Serratia marcescens bacterial isolates. Of the 17 phages, ECWG5_I_MbraKat_OJ_25 and ECWG5_RKirUS_OJ_25 phages were the most effective against the tested bacterial strains, with 75% lytic ability. These two phages could lyse ESBL E. coli. The isolated phages were stable at 4 °C and 37 °C, and their dilution end point range was 10-6 to 10-10, suggesting that the phage stocks were still potent and able to infect bacteria at relatively high dilutions. Conclusion The study isolated 17 phages from wastewater and the river water, which showed lytic activity against selected clinical Gram-positive and Gram-negative bacterial isolates. This study offers preliminary insights into the environmentally isolated phages, enabling researchers to further characterize and assess their potential application in phage-based clinical interventions, particularly for the management of drug-resistant pathogenic bacteria.

Keywords:  bacteria; host range; lytic bacteriophages; river; waste water

DOI:  https://doi.org/10.7759/cureus.102524
Wound Repair Regen. 2026 Mar-Apr;34(2):34(2): e70140

Transcriptomics in Venous Leg Ulcers (VLU): A Systematic Review.

Chien Lin Soh, Kia Hau Matthew Tan, Alun Huw Davies, Sarah Onida.

  Venous leg ulcers (VLUs) are chronic wounds in the lower limbs that cause significant morbidity. The underlying biology underpinning non-healing in VLUs is still poorly understood and differences in transcriptomic profiles may help elucidate biological pathways involved in wound chronicity. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Studies were included if transcriptomes from adults with confirmed VLU were described. A search of EMBASE, OVID and PubMed between 1 January 1994 and 17 August 2024 yielded 429 articles; 34 studies were included after full-text screening by two independent reviewers. Twenty-nine studies investigated coding messenger RNA (mRNA) expression, while five studies investigated non-coding RNA. Samples were obtained from wound biopsies (n = 31) or whole blood (n = 3). There were variations in mRNA expression across comparisons between patients with VLUs and controls such as tissue from other patients, tissue from different sites and treated tissues. Altered levels of mRNA transcripts suggest chronic inflammatory states, hyperproliferation and reduced wound healing. Studies exploring non-coding RNAs described their roles in regulating wound repair. Paired analyses of microRNA expression demonstrate impact on RNA expression profiles, with effects on inhibition of wound healing. Transcriptomic analysis provides new insights into the pathophysiology of the development and healing of VLUs. Further development of RNA biomarkers and gene expression profiles can improve diagnosis and prognostication of VLUs, but heterogeneity of current data may make it difficult to draw clinical significance. Trial Registration: PROSPERO: CRD42024580526.

Keywords:  RNA; transcriptomics; venous disease; venous insufficiency; venous ulcers

DOI:  https://doi.org/10.1111/wrr.70140