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24 pages, 2719 KB  
Article
Preliminary Study of Potential Hydrocarbon-Degrading Bacteria Identified by 16S rRNA Sequencing in Haina Port Water Samples, Dominican Republic
by Yameiri Mena, Jose Navarro-Pedreño, José David Hernández-Martich, Manuel M. Jordán, Víctor Sala-Sala, Ignacio Gómez-Lucas and Ana Pérez-Gimeno
Water 2026, 18(3), 307; https://doi.org/10.3390/w18030307 (registering DOI) - 25 Jan 2026
Abstract
Microorganisms live in a wide range of environments, performing diverse roles either independently or in association with other organisms forming consortia. This study is focused on those with the ability to bioremediate environments contaminated with petroleum hydrocarbons (PHCs), that is, the case of [...] Read more.
Microorganisms live in a wide range of environments, performing diverse roles either independently or in association with other organisms forming consortia. This study is focused on those with the ability to bioremediate environments contaminated with petroleum hydrocarbons (PHCs), that is, the case of bacteria, fungi, algae, and consortia. PHC contamination constitutes a major global environmental issue, and presents a serious ecological risk. This research was conducted in the coastal waters of Haina Port (Dominican Republic) and the main objective was to characterise the bacterial communities with bioremediation capacity by sequencing the 16S rRNA. The samples were collected in sterile conditions, and physicochemical and molecular analyses were conducted. The results revealed the composition and distribution of bacterial communities in the area. At the phylum level, Proteobacteria is the dominant group, accounting for 70–90% of the community. At the class level, Gammaproteobacteria is the predominant group, followed by Alphaproteobacteria which ranks second in relative abundance. Bacillaceae appears as the most abundant family at most points. This 16S rRNA survey provides a taxonomic baseline of the microbial community, identifying taxa with documented degradative potential. Future functional analyses and culture studies are required to quantify and confirm the active metabolic pathways of the detected microorganisms. Full article
(This article belongs to the Special Issue Water Quality, Wastewater Treatment and Water Recycling, 2nd Edition)
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15 pages, 4429 KB  
Article
Maternal Poly (I:C)-Induced Placental Inflammation and Endocrine Dysfunction Are Associated with Disrupted Corticogenesis in Mouse Offspring
by Catherine Zhou, Callan Baldwin, Shuying Lin, Aaron Hayes, Kathleen Carter, Lir-Wan Fan, Abhay Bhatt and Yi Pang
Brain Sci. 2026, 16(2), 126; https://doi.org/10.3390/brainsci16020126 (registering DOI) - 24 Jan 2026
Abstract
Background/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking [...] Read more.
Background/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring. Methods: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6. Results: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6. Conclusions: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring. Full article
(This article belongs to the Special Issue Inflammation and Central Nervous System)
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18 pages, 2151 KB  
Article
Silent Waterborne Carriers of Carbapenem-Resistant Gram-Negative Bacilli and Antimicrobial Resistance Genes in Rio de Janeiro’s Aquatic Ecosystems
by Laura Brandão Martins, Marcos Tavares Carneiro, Kéren Vieira-Alcântara, Thiago Pavoni Gomes Chagas and Viviane Zahner
Antibiotics 2026, 15(2), 115; https://doi.org/10.3390/antibiotics15020115 - 23 Jan 2026
Abstract
Background/Objectives: Water pollution caused by human activities disrupts ecosystems and promotes the spread of antimicrobial resistance genes (ARGs), posing a public health threat. This study investigated the presence of resistant Gram-negative bacteria and resistance genes in water from two sites occasionally exposed [...] Read more.
Background/Objectives: Water pollution caused by human activities disrupts ecosystems and promotes the spread of antimicrobial resistance genes (ARGs), posing a public health threat. This study investigated the presence of resistant Gram-negative bacteria and resistance genes in water from two sites occasionally exposed to domestic and hospital effluents, the Carioca River (CR) and Rodrigo de Freitas Lagoon (RFL), both used for recreation. Methods: Physicochemical parameters and coliform levels were measured. Bacterial isolates were identified by Matrix-Assisted Laser Desorption Ionization–Time-of-Flight Mass Spectrometry (MALDI-TOF MS) and tested for antimicrobial susceptibility using disk diffusion. The Minimum Inhibitory Concentration (MIC) was determined using the E-test® and broth microdilution methods. PCR was used to detect carbapenem resistance and other ARGs from the DNA of bacterial isolates obtained from water samples. Results: CR presented signs of environmental degradation, with low dissolved oxygen and high coliform counts. One Citrobacter braakii isolate showed resistance to all tested antimicrobials, raising concern for untreatable infections. Carbapenem-resistant isolates accounted for 49.4% of the total, harboring blaKPC (20%), blaTEM (5%), blaVIM (5%), and blaSPM (5%). The intl1 gene was found in 10% of isolates, indicating potential horizontal gene transfer. Conclusions: The findings from a one-day sampling reveal the presence of multidrug-resistant bacteria that carry antimicrobial resistance genes in polluted aquatic systems. These highlight the connection between water contamination and antimicrobial resistance. The evidence underscores the urgent need for environmental monitoring and effective management strategies to reduce public health risks. Full article
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27 pages, 3905 KB  
Review
Silent Threat Evolution: Critically Important Carbapenem and Colistin Resistance Genes in the Natural Aquatic Environment
by Małgorzata Czatzkowska and Damian Rolbiecki
Antibiotics 2026, 15(2), 113; https://doi.org/10.3390/antibiotics15020113 - 23 Jan 2026
Viewed by 22
Abstract
The rise in antimicrobial resistance (AMR) among the most clinically significant bacteria presents a global threat. The coexistence of resistance mechanisms to both carbapenems and colistin is particularly concerning, as these are last-line treatments, specifically reserved for the most challenging infections caused by [...] Read more.
The rise in antimicrobial resistance (AMR) among the most clinically significant bacteria presents a global threat. The coexistence of resistance mechanisms to both carbapenems and colistin is particularly concerning, as these are last-line treatments, specifically reserved for the most challenging infections caused by clinically multidrug-resistant Enterobacterales. Natural aquatic environments have become environmental reservoirs for the transmission of AMR, particularly concerning mechanisms against these two types of critically important drugs. The crucial role of environmental settings as a driving force for the spread and evolution of AMR associated with these drugs is underestimated, and scientific knowledge on this topic is limited. This review aims to fill an important gap in the scientific literature and comprehensively consolidate the available data on carbapenem- and colistin-associated AMR in the aquatic environment. This study provides a comprehensive synthesis of the current knowledge by integrating bibliographic data with a detailed genomic analysis of 278 bacterial genomes sourced from natural waters. It explores the distribution of carbapenemase and mobile colistin resistance (mcr) genes, identifying their hosts, geographical spread, and complex gene–plasmid–host associations. This review distinguishes two critical host groups for genes that provide resistance to last-resort drugs, Enterobacterales and autochthonous aquatic microbiota, highlighting both confirmed and potential interactions between them. Crucially, genomic analysis highlights the alarming co-occurrence of carbapenem and colistin resistance in single cells and on single plasmids, contributing to the spread of multidrug resistance phenotypes. These findings clearly indicate that aquatic environments are not merely passive recipients but active, evolving hubs for high-risk AMR determinants. Future research should focus on the interplay between allochthonous vectors and autochthonous microbiota to better understand the long-term stabilization of carbapenemase and mcr genes. Such efforts, combined with advanced sequencing technologies, are essential to ensure that carbapenems and colistin remain viable treatment options in clinical settings. Full article
(This article belongs to the Special Issue Origins and Evolution of Antibiotic Resistance in the Environment)
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9 pages, 3707 KB  
Case Report
Limb-Sparing Reconstruction for Chronic Non-Bacterial Osteomyelitis of the Toe in a Pediatric Athlete: A Case Report
by Alan E. Augdahl, Thuy-Mi Le, Aamir Ahmed and Rahul Mittal
Reports 2026, 9(1), 32; https://doi.org/10.3390/reports9010032 - 23 Jan 2026
Viewed by 17
Abstract
Background and Clinical Significance: Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that primarily affects children and adolescents, with females more frequently impacted. The condition remains poorly understood, though cytokine dysregulation and inflammasome activation are believed to contribute to its pathogenesis. [...] Read more.
Background and Clinical Significance: Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that primarily affects children and adolescents, with females more frequently impacted. The condition remains poorly understood, though cytokine dysregulation and inflammasome activation are believed to contribute to its pathogenesis. Clinically, CNO is often difficult to distinguish from infectious osteomyelitis, as presenting symptoms such as bone pain, swelling, and functional limitation are nonspecific, while cultures are frequently negative. As a diagnosis of exclusion, delays in recognition can lead to prolonged or unnecessary antibiotic exposure and uncertainty in management. Case Presentation: A 14-year-old male with a history of left second toe osteomyelitis initially diagnosed in 2021. Despite negative cultures and limited histopathologic findings, he received multiple antibiotic courses with little improvement, and the digit remained chronically swollen. Three years later, a repeat evaluation revealed osseous resorption of the middle and distal phalanges, and a biopsy confirmed acute and mild chronic fibrosing osteomyelitis, consistent with CNO. Given the risk of progression and possible amputation, surgical reconstruction was pursued. The patient underwent autologous calcaneal bone grafting with digital fusion using a K-wire. At three months and one year postoperatively, radiographs demonstrated solid fusion of the digit with maintained activity and resolution of pain. Conclusions: This case emphasizes the diagnostic complexity of CNO and the importance of considering it in children with culture-negative or recurrent osteomyelitis. It further illustrates how timely surgical intervention can preserve function and quality of life while avoiding unnecessary amputation. Full article
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55 pages, 3698 KB  
Review
Navigating the Challenges of Metallopharmaceutical Agents: Strategies and Predictive Modeling for Skin Cancer Therapy
by Fernanda van Petten Vasconcelos Azevedo, Ana Lúcia Tasca Gois Ruiz, Diego Samuel Rodrigues, Douglas Hideki Nakahata, Raphael Enoque Ferraz de Paiva, Daniele Ribeiro de Araujo, Ana Carola de La Via, Wendel Andrade Alves, Michelle Barreto Requena, Cristina Kurachi, Mirian Denise Stringasci, José Dirceu Vollet-, Wilton Rogério Lustri, Vanderlei Salvador Bagnato, Camilla Abbehausen, Pedro Paulo Corbi and Carmen Silvia Passos Lima
Pharmaceutics 2026, 18(2), 145; https://doi.org/10.3390/pharmaceutics18020145 - 23 Jan 2026
Viewed by 30
Abstract
Skin cancer (SC) is the most prevalent malignancy worldwide, with subtypes varying in aggressiveness: basal cell carcinoma tends to be locally invasive, squamous cell carcinoma has a higher metastatic risk, and melanoma remains the deadliest form. Current treatments such as surgery, radiotherapy, and [...] Read more.
Skin cancer (SC) is the most prevalent malignancy worldwide, with subtypes varying in aggressiveness: basal cell carcinoma tends to be locally invasive, squamous cell carcinoma has a higher metastatic risk, and melanoma remains the deadliest form. Current treatments such as surgery, radiotherapy, and systemic chemotherapy are associated with aesthetic and functional morbidity, recurrence, and/or systemic toxicity. Although targeted therapies and immunotherapies offer clinical benefits, their high cost and limited accessibility underscore the need for innovative, affordable alternatives. Metal-based compounds (metallopharmaceuticals) are promising anticancer agents due to their ability to induce oxidative stress, modulate redox pathways, and interact with DNA. However, clinical translation has been limited by poor aqueous solubility, rapid degradation, and low skin permeability. This review discusses the most recent preclinical findings on gold, silver, platinum, palladium, ruthenium, vanadium, and copper complexes, mainly in topical and systemic treatments of SC. Advances in chemical and physical enhancers, such as hydrogels and microneedles, and in drug delivery systems, including bacterial nanocellulose membranes and nanoparticles, as well as liposomes and micelles, for enhancing skin permeation and protecting the integrity of metal complexes are also discussed. Additionally, we examine the contribution of photodynamic therapy to SC treatment and the use of mathematical and computational modeling to simulate skin drug transport, predict biodistribution, and support rational nanocarrier design. Altogether, these strategies aim to bridge the gap between physicochemical innovation and clinical applicability, paving the way for more selective, stable, and cost-effective SC treatments. Full article
(This article belongs to the Special Issue Dosage Form Design and Delivery Therapy for Skin Disorders)
15 pages, 685 KB  
Review
Anti-Chlamydia trachomatis Host Defence Arsenal Within the Cervicovaginal Environment
by Simone Filardo, Giulia Chicarella, Rosa Sessa and Marisa Di Pietro
Int. J. Mol. Sci. 2026, 27(2), 1115; https://doi.org/10.3390/ijms27021115 - 22 Jan 2026
Viewed by 7
Abstract
Chlamydia trachomatis has a significant impact on public health, especially among adolescents and young women; it primarily affects urogenital epithelial cells, leading to cervicitis and urethritis, with >90% of cases showing no symptoms. Consequently, chlamydial infections are commonly misdiagnosed, and, if untreated, they [...] Read more.
Chlamydia trachomatis has a significant impact on public health, especially among adolescents and young women; it primarily affects urogenital epithelial cells, leading to cervicitis and urethritis, with >90% of cases showing no symptoms. Consequently, chlamydial infections are commonly misdiagnosed, and, if untreated, they may result in severe reproductive sequelae including infertility. A better understanding of C. trachomatis cell biology and bacterial–host cell interactions may be helpful to identify strategies able to counter its transmission among the population, as well as its dissemination in reproductive tissues, reducing the risk of developing severe reproductive sequelae. Therefore, the present review aims to summarize the evidence on the interplay between C. trachomatis and the host defence factors within the cervicovaginal environment. The sophisticated strategies employed by this clinically significant pathogen to counteract these mechanisms are also discussed. In the literature, the main defence factors include the microbiota dominated by Lactobacillus crispatus and several molecules like lactoferrin, able to protect the cervicovaginal microenvironment against C. trachomatis through several mechanisms (e.g., EB coaggregation and competitive exclusion, as well as anti-inflammatory activity). However, the major player in clearing chlamydial infections remains the interferon-gamma (IFN-γ) produced by natural killer and T cells, via the depletion of critical nutrients for C. trachomatis such as tryptophan, or via the ubiquitylation and destruction of chlamydial inclusions. Full article
(This article belongs to the Special Issue Chlamydia trachomatis Pathogenicity and Disease (Third Edition))
16 pages, 2709 KB  
Article
Occurrence, Seasonal Variation, and Microbial Drivers of Antibiotic Resistance Genes in a Residential Secondary Water Supply System
by Huaiyu Tian, Yu Zhou, Dawei Zhang and Weiying Li
Water 2026, 18(2), 281; https://doi.org/10.3390/w18020281 - 22 Jan 2026
Viewed by 18
Abstract
The widespread use of antibiotics has led to the persistence of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in drinking water systems, posing potential public health risks at the point of use. In this study, a residential secondary water supply system (SWSS) [...] Read more.
The widespread use of antibiotics has led to the persistence of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in drinking water systems, posing potential public health risks at the point of use. In this study, a residential secondary water supply system (SWSS) in eastern China was investigated over one year to characterize microbial communities, ARB and ARG occurrence, and their associations with water quality in bulk water and biofilms. Culture-based methods, flow cytometry, quantitative PCR, and high-throughput 16S rRNA and ITS sequencing were applied. Although conventional treatment removed 94.8% of total bacteria, significant microbial regrowth occurred during secondary distribution, with the highest heterotrophic plate counts observed in rooftop storage tanks (up to 4718 CFU/mL). ARG concentrations increased along the distribution line, and the class 1 integron intI1 was enriched in downstream locations, indicating enhanced horizontal gene transfer potential. Sulfonamide resistance genes dominated the resistome, accounting for more than 60% of total ARG abundance in water samples. Seasonally, ARG levels were higher in autumn and winter, coinciding with elevated disinfectant residuals and lower temperatures. Chlorine was negatively associated with total bacterial abundance, while positive correlations were observed with the relative abundance of several ARGs when normalized to bacterial biomass, suggesting selective pressure under oxidative stress. Turbidity and bacterial abundance were positively correlated with ARB, particularly sulfonamide-resistant bacteria. Biofilms exhibited more stable microbial communities and provided microhabitats that facilitated microbial persistence. Notably, fungal abundance showed strong positive correlations with multiple ARGs, implying that microbial interactions may indirectly contribute to ARG persistence in SWSSs. These findings highlight the role of secondary distribution conditions, disinfectant pressure, and microbial interactions in shaping resistance risks in residential water supply systems, and provide insights for improving microbial risk management at the point of consumption. Full article
(This article belongs to the Special Issue Advances in Control Technologies for Emerging Contaminants in Water)
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17 pages, 3175 KB  
Article
Flavonoid-Rich Cyperus esculentus Extracts Disrupt Cellular and Metabolic Functions in Staphylococcus aureus
by Yaning Zhang, Zhengdong Ma, Xuzhe Wang, Qilong Jiang, Xue Kang and Hongmei Gao
Microorganisms 2026, 14(1), 260; https://doi.org/10.3390/microorganisms14010260 - 22 Jan 2026
Viewed by 20
Abstract
The escalating threat of antibiotic resistance, particularly from Staphylococcus aureus (S. aureus), has become a critical challenge in both public health and animal husbandry. The extensive use of conventional antibiotics in livestock production accelerates the emergence of resistant strains, heightening risks [...] Read more.
The escalating threat of antibiotic resistance, particularly from Staphylococcus aureus (S. aureus), has become a critical challenge in both public health and animal husbandry. The extensive use of conventional antibiotics in livestock production accelerates the emergence of resistant strains, heightening risks to food safety and human health. Although plant-derived bioactive compounds are increasingly recognized as promising alternatives to synthetic antimicrobials, the mechanisms underlying their efficacy—and the potential for synergistic action among different plant parts—remain poorly understood. In particular, the antibacterial interactions among extracts from different tissues of Cyperus esculentus L. (C. esculentus), a plant rich in flavonoids and phenolics, have yet to be systematically evaluated. Here, we investigated the antibacterial properties and mechanisms of ethanol extracts from the tubers, stems–leaves and their mixture of C. esculentus against S. aureus. Using Oxford cup diffusion assays, scanning electron microscopy (SEM), bacterial growth kinetics, and untargeted metabolomics, we assessed both phenotypic inhibition and metabolic disruption. The mixed extract exhibited the strongest antibacterial effect, producing a 26.15 mm inhibition zone—approximately 7% greater than that of single-part extracts—and induced cell wall rupture and disintegration as observed by SEM. Growth curve analyses revealed time-dependent bacterial suppression, while metabolomic profiling identified 845 differential metabolites, indicating disturbances in amino acid, lipid, and nucleotide metabolism. Flavonoids such as acacetin, diosmetin, naringenin, and silybin A were identified as principal active compounds contributing to these effects. Full article
(This article belongs to the Special Issue Microorganisms in Silage—2nd Edition)
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14 pages, 1099 KB  
Article
Distinct Gut Microbiome Profiles Underlying Cardiometabolic Risk Phenotypes in Individuals with Obesity
by Iveta Nedeva, Yavor Assyov, Veselka Duleva, Vera Karamfilova, Zdravko Kamenov, Julian Naydenov, Teodora Handjieva-Darlenska, Venelin Denchev, Alexander Kolevski, Victoria Pencheva and Vlayko Vodenicharov
Nutrients 2026, 18(2), 353; https://doi.org/10.3390/nu18020353 - 22 Jan 2026
Viewed by 13
Abstract
Background: Obesity-related cardiometabolic disorders have been linked to alterations in selected gut microbiome components, yet clinically relevant microbial signatures remain incompletely defined. Objectives: This study investigated associations between selected gut bacterial taxa and cardiometabolic risk phenotypes in individuals with obesity. Methods: [...] Read more.
Background: Obesity-related cardiometabolic disorders have been linked to alterations in selected gut microbiome components, yet clinically relevant microbial signatures remain incompletely defined. Objectives: This study investigated associations between selected gut bacterial taxa and cardiometabolic risk phenotypes in individuals with obesity. Methods: In this cross-sectional study, 100 adults with obesity were stratified according to metabolic syndrome status. Gut microbiome composition was assessed using targeted multiplex real-time PCR of functionally relevant bacterial taxa. Associations with anthropometric and cardiometabolic parameters were examined using correlation analysis, ROC curves, and multivariable logistic regression models. Results: Reduced relative abundance of Lachnospiraceae was associated with metabolic syndrome, lower Faecalibacterium abundance with arterial hypertension, and increased Prevotella abundance with dyslipidemia. ROC analyses identified cohort-specific discriminative thresholds with moderate accuracy. Conclusions: Selected taxon-specific gut microbiome signatures are associated with cardiometabolic risk phenotypes in obesity. These findings are exploratory and require validation in longitudinal and independent cohorts. Full article
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13 pages, 548 KB  
Review
A Clinician’s Update on Infection Risk in Patients Receiving Biologic and Targeted Synthetic DMARDs for Autoimmune Disease
by Hilal Abdessamad
Rheumato 2026, 6(1), 4; https://doi.org/10.3390/rheumato6010004 - 22 Jan 2026
Viewed by 20
Abstract
Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent [...] Read more.
Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent literature was conducted to characterize infectious complications associated with modern immunomodulatory biologic agents, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, a systematic search was performed on Scopus, Science Direct, and PubMed for studies published since 2023. Inclusion criteria focused on adult human subjects, exposure to immunomodulatory therapy, and reported infectious outcomes. Studies focusing exclusively on antineoplastic agents without established use in autoimmune diseases were excluded. After screening 1046 unique records, 16 studies were included in the final review. Findings: High-dose glucocorticoids remain a primary driver of serious infections across autoimmune diseases. Newer agents present mechanism-specific risk profiles. JAK inhibitors are associated with herpes zoster, while TNF-α inhibitors are linked to opportunistic bacterial infections and reactivation of granulomatous infections. B-cell depletion with rituximab correlates with hypogammaglobulinemia and its associated infections, whereas belimumab may offer a lower infection risk in non-renal SLE. Recent post hoc analyses (2023–2025) quantify the elevated risk of herpes zoster with JAK inhibitors compared to TNF inhibitors, particularly in older populations. Conclusions: The infectious risk associated with biologic and targeted DMARDs varies by mechanism. While glucocorticoids remain a primary driver of serious infections, newer data highlights specific vulnerabilities with JAK inhibitors (herpes zoster) and B-cell depletion (hypogammaglobulinemia) that require targeted risk stratification. This review shows the urgent need for individualized risk stratification, targeted prophylaxis (e.g., for Pneumocystis or zoster), and pre-therapy screening to balance therapeutic efficacy with patient safety. Full article
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21 pages, 1377 KB  
Systematic Review
Current Challenges and Long-Term Outcomes in Corneal Transplantation in Infectious Keratitis—A Systematic Review
by Ancuța-Georgiana Onofrei, Alina Gabriela Gheorghe, Ana Maria Dascalu, Bogdan Mihai Cristea, Sinziana Istrate, Ana Maria Arghirescu, Dragos Serban, Corneliu Tudor, Paul Lorin Stoica, Marina-Ionela Nedea and Dan Dumitrescu
J. Clin. Med. 2026, 15(2), 871; https://doi.org/10.3390/jcm15020871 - 21 Jan 2026
Viewed by 161
Abstract
Background/Objectives: Infectious keratitis remains a major cause of blindness worldwide, and many cases progress to therapeutic keratoplasty despite advances in antimicrobial therapy. This systematic review aims to evaluate the outcomes of therapeutic keratoplasty in microbial keratitis and examine factors influencing anatomical success, graft [...] Read more.
Background/Objectives: Infectious keratitis remains a major cause of blindness worldwide, and many cases progress to therapeutic keratoplasty despite advances in antimicrobial therapy. This systematic review aims to evaluate the outcomes of therapeutic keratoplasty in microbial keratitis and examine factors influencing anatomical success, graft survival, and visual rehabilitation. Methods: A systematic review was conducted following PRISMA guidelines, including English-language studies, published between 2000 and 2025. Studies with ≥10 eyes and ≥6 months follow-up were included. Data on infection control, graft clarity, anatomical success, visual acuity, and complications were extracted. Results: Fourteen studies encompassing 1527 eyes were analyzed. TPK accounted for 89% of procedures; DALK was used selectively for anterior or mid-stromal infections. Overall infection control ranged from 69 to 100%, with globe preservation in 85–100% of cases. Bacterial keratitis had higher cure rates and graft clarity than fungal or Acanthamoeba keratitis. Larger grafts (>8 mm) and deep stromal involvement were associated with increased graft rejection and postoperative complications. DALK offered higher graft survival and lower immunologic risk when the endothelium was spared. Visual outcomes were generally limited, reflecting preoperative disease severity, timing of surgery, and postoperative immunomodulation constraints. Early surgical intervention improved anatomical outcomes in severe fungal keratitis. Conclusions: Therapeutic keratoplasty is an effective globe-preserving intervention in advanced microbial keratitis, but with limited functional outcomes. Further prospective studies are needed to refine surgical indications, postoperative management, and long-term functional results. Full article
(This article belongs to the Special Issue New Insights in Ophthalmic Surgery)
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15 pages, 1411 KB  
Article
Utilizing MALDI-TOF MS for Legionella pneumophila Subspecies Typing and Classification
by Lana Madagi, Shimon Edelstein, Hila Ben-Amram and Yehonatan Sharaby
Water 2026, 18(2), 269; https://doi.org/10.3390/w18020269 - 21 Jan 2026
Viewed by 75
Abstract
Legionella pneumophila (L. pneumophila), the primary causative agent of Legionnaires’ disease, is a waterborne bacterial pathogen that poses significant public health concern. This opportunistic pathogen commonly inhabits both natural and man-made water systems, particularly drinking water distribution systems (DWDSs), where it [...] Read more.
Legionella pneumophila (L. pneumophila), the primary causative agent of Legionnaires’ disease, is a waterborne bacterial pathogen that poses significant public health concern. This opportunistic pathogen commonly inhabits both natural and man-made water systems, particularly drinking water distribution systems (DWDSs), where it can proliferate and pose a risk to human health. In this study, we evaluated the potential of Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for rapid and accurate subtyping of L. pneumophila. Our analysis included 70 L. pneumophila strains collected from the Middle East, representing one of the largest and most comprehensive MALDI-TOF MS-based subtyping of strains from this geographically underrepresented region. These strains, representing three Multi-Locus Variable Number Tandem Repeat Analysis (MLVA-8) genotypic groups (GT4, GT6, and GT15), have been extensively characterized in previous studies for their virulence traits, cytotoxicity patterns, and antimicrobial susceptibility profiles. Our findings revealed distinct genotype-associated spectral signatures with 30 discriminatory m/z peaks (p ≤ 0.005). These markers enabled accurate genotype-level classification, achieving over 85% classification accuracy with a Random Forest model and over 71% accuracy using a Decision Tree algorithm. Importantly, the m/z peak at 5358 was uniquely present in the GT15 strains, whereas m/z 5353 was consistently detected in both GT4 and GT6 isolates, demonstrating the potential of specific mass peaks to serve as reliable genotype markers. Furthermore, GT15 strains consistently formed a separate cluster in both Principal Component Analysis (PCA) and hierarchical analyses, whereas GT4 and GT6 exhibited partial overlap, reflecting their exceptionally high genomic similarity. Full article
(This article belongs to the Section Water and One Health)
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19 pages, 4422 KB  
Article
In Vitro and In Vivo Efficacy of Epithelial Barrier-Promoting Barriolides as Potential Therapy for Ulcerative Colitis
by Jon P. Joelsson, Michael J. Parnham, Laurène Froment, Aude Rapet, Andreas Hugi, Janick Stucki, Nina Hobi and Jennifer A. Kricker
Biomedicines 2026, 14(1), 237; https://doi.org/10.3390/biomedicines14010237 - 21 Jan 2026
Viewed by 94
Abstract
Background/Objectives: Ulcerative colitis (UC) is an inflammatory bowel disease and a major cause of ulcers and chronic inflammation in the colon and rectum. Recurring symptoms include abdominal pain, rectal bleeding, and diarrhoea, and patients with UC are at a higher risk of [...] Read more.
Background/Objectives: Ulcerative colitis (UC) is an inflammatory bowel disease and a major cause of ulcers and chronic inflammation in the colon and rectum. Recurring symptoms include abdominal pain, rectal bleeding, and diarrhoea, and patients with UC are at a higher risk of developing comorbidities such as colorectal cancer and poor mental health. In UC, the decreased diversity and changed metabolic profile of gut microbiota, along with a diminished mucus layer, leads to disruption of the underlying epithelial barrier, with an ensuing excessive and detrimental inflammatory response. Treatment options currently rely on drugs that reduce the inflammation, but less emphasis has been placed on improving the resilience of the epithelial barrier. Macrolide antibiotics exhibit epithelial barrier-enhancing capacities unrelated to their antibacterial properties. Methods: We investigated two novel barriolides, macrolides with reduced antibacterial effects in common bacterial strains. Gut epithelial cell barrier resistance in the Caco-2 cell line, with and without co-culture with mucus-producing HT-29 cells, was increased when treated with barriolides. Using AXGut-on-Chip technology with inflammatory cytokine-stimulated Caco-2/HT-29 co-cultures, the effectiveness of the barriolides was confirmed. Lastly, we reveal the barrier-enhancing and inflammation-reducing effects of the barriolides in a dextran-sulphate sodium (DSS)-induced colitis mouse model. Results: We show the predictive power of the novel AXGut-on-Chip system and the effectiveness of the novel barriolides. Indications include reduced inflammatory response, increased epithelial barrier and decreased overall clinical score. Conclusions: The results of this study indicate the notion that barriolides could be used as a treatment option for UC. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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Article
Serum CCL5 in Liver Transplant Candidates: A Potential Marker of Portal Hypertension, Not Cardiovascular Risk
by Teodora Radu, Speranța M. Iacob, Ioana Manea and Liliana S. Gheorghe
Gastrointest. Disord. 2026, 8(1), 7; https://doi.org/10.3390/gidisord8010007 - 21 Jan 2026
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Abstract
Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular [...] Read more.
Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM® SPSS® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD. Full article
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