Search Results (559)

The increasing antimicrobial resistance of T. pyogenes, one of the principal pathogens associated with endometritis, presents a formidable challenge in veterinary medicine. Astragaloside IV (AS-IV) is a triterpene saponin compound isolated from the traditional Chinese medicine Astragalus membranaceus. While recognized as the primary bioactive constituent of Astragalus membranaceus with diverse pharmacological properties, its potential to counteract T. pyogenes-induced endometritis has yet to be elucidated. In the current study, T. pyogenes infection models were successfully established in both mouse uteri and cultured goat endometrial epithelial cells (gEECs). Integrating histopathology, molecular biology and transcriptomic technology, this study characterized the multifaceted biological effects of AS-IV. Transcriptomic analysis indicates that the regulatory effects of AS-IV on T. pyogenes-induced infection are primarily associated with the enrichment of signaling pathways related to inflammation, apoptosis, and oxidative stress. Subsequent validation demonstrated that AS-IV treatment effectively alleviated T. pyogenes-induced endometrial damage by suppressing inflammation, apoptosis, and oxidative stress. These effects were mediated through Nrf2 and its downstream target HO-1, a mechanism further confirmed by the loss of protection upon Nrf2 inhibition. In summary, AS-IV protects the endometrium against T. pyogenes-induced inflammatory and oxidative damage by activating the Nrf2/HO-1 signaling pathway. Full article

Objective: This study aimed to quantitatively evaluate five opportunistic respiratory pathogens among individuals, with or without dentures, who have either healthy or diseased periodontal conditions. Methods: Saliva samples were obtained from 24 older adults. DNA extraction was performed, followed by a quantitative Polymerase Chain Reaction targeting five opportunistic respiratory pathogens, namely Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, Klebsiella pneumoniae, and Streptococcus agalactiae. The abundance of opportunistic pathogens among the four groups [denture-wearing with active periodontal disease (DAP), non-denture-wearing with active periodontal disease (NDAP), denture-wearing with stable periodontal health (DSP), and non-denture-wearing with stable periodontal health (NDSP)] were compared. Results: Saliva samples of all participants (100%) carried at least one opportunistic respiratory pathogen. Of the five pathogens, S. aureus, P. aeruginosa, K. pneumoniae, and S. agalactiae were present in more than 50% of the samples. A significant difference in the bacterial load of K. pneumoniae and P. aeruginosa was observed (p < 0.05). The quantity of P. aeruginosa in the NDAP group was significantly lower than the DSP group. However, for K. pneumoniae, no significant differences between the groups were detected. Conclusions: In this small pilot cohort, a relatively high prevalence and substantial microbial load of opportunistic respiratory pathogens were identified in the saliva of older adults. On the basis of these preliminary findings, optimal oral and denture hygiene care is suggested as a potential approach to reduce the presence and burden of respiratory pathogens in this population, although larger studies are required to confirm these associations and determine their clinical significance. Full article

Oral squamous cell carcinoma (OSCC) accounts for the majority of feline oral neoplasms and carries a poor prognosis; however, the oral microbiome in affected cats remains poorly characterized. This study aimed to preliminarily describe the oral bacterial communities of cats with OSCC and compare them with those of clinically healthy cats using DNA amplicon sequencing. Oral swabs were collected from cats with OSCC, including tumor surfaces, tumor cut surfaces, and clinically normal mucosa distant from the tumor (n = 20 total samples), and from the gingival margin of healthy cats (n = 12). DNA was extracted and full-length 16S rRNA gene sequencing was performed to assess microbial composition and diversity. Cats with OSCC exhibited significant alterations in oral microbiota compared with healthy controls, including reduced alpha diversity, distinct beta-diversity clustering, and consistent taxonomic shifts. Healthy cats displayed a relatively conserved core microbiome dominated by Porphyromonas spp., Bacteroides, Pasteurellaceae, Helcococcus, and Moraxella. In contrast, OSCC-associated samples showed increased relative abundances of anaerobic and disease-associated taxa, including Filifactor villosus, Bacteroides pyogenes, Odoribacter denticanis, Porphyromonas circumdentaria, and members of the Pasteurellaceae. These findings provide the first description of the oral microbiota associated with feline OSCC and demonstrate exploratory microbial differences between health and disease. Full article

Essential oils are widely used in cosmetic products and are valued for their antimicrobial properties. In this study, the in vitro antimicrobial activity of five pure essential oils (EOs) and five commercially available EO blends was comparatively evaluated against six skin-associated pathogens: Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, Candida lusitaniae and Candida guilliermondii. Chemical profiling of volatile constituents was performed using gas chromatography–mass spectrometry; antimicrobial activity was assessed by broth microdilution to determine minimum inhibitory concentration (MIC), as well as spot-inoculation to determine minimum bactericidal concentration (MBC). Results revealed microorganism-dependent inhibitory and bactericidal activity of the tested essential oils. Candida spp. and E. coli were the most susceptible microorganisms, whereas P. aeruginosa exhibited the lowest susceptibility to essential oils. Pinus sylvestris showed comparatively lower MIC and MBC values across most tested microorganisms. Commercial EO blends showed comparable antimicrobial activity to individual essential oils. Overall, this study provides a comparative in vitro screening of selected essential oils and commercial blends relevant to cosmetic applications, indicating that EO blends do not exhibit superior antimicrobial activity over pure oils under the tested conditions. Full article

Bacterial biofilms play a major role in delayed wound-healing and in the development of chronic, non-healing wounds. Natural, plant-based agents, which can eradicate bacterial biofilms, are alternatives to antibiotics and antiseptics in the treatment of bacterially contaminated wounds. Bacterial wound biofilms are three-dimensional and complex microbial communities. Therefore, in this study, we used a three-dimensional fibrin-gel wound biofilm (FGWB) model to compare a commonly used natural agent in wound care, hypochlorous acid (HOCl), to a combination of two natural plant-based agents, polygalacturonic acid (PG) and caprylic acid (CAP) (PG + CAP), for their abilities to eradicate resistant bacterial biofilms of common wound pathogens methicillin resistant Staphylococcus aureus (MRSA), multi-drug resistant (MDR) Pseudomonas aeruginosa, metallo β-Lactamase Escherichia coli, and Streptococcus pyogenes. PG + CAP produced a significantly greater reduction in viable organisms when compared to HOCL (p ≤ 0.05) against all tested bacterial isolates. PG + CAP was highly effective against biofilms of all resistant bacterial isolates and is a promising option that merits further study for treating chronic wounds contaminated with bacterial biofilms. Full article

Objectives. Pancreatic cancer remains one of the most lethal malignancies, and the lack of effective therapies highlights the need for novel treatment strategies. In this study, we evaluated the antitumor potential of the attenuated Streptococcus pyogenes strain GURSA1—engineered to knockout the M protein completely—in a murine model of orthotopically transplanted pancreatic ductal adenocarcinoma. Methods. Female C57Bl/6 mice received intratumoral injections of GURSA1 at doses of 5 × 10⁵ or 1 × 10⁶ CFU per animal. Animal survival, body weight, tumor engraftment, metastasis intensity, tumor mass and volume, and hematological, biochemical, histological, and microbiological parameters were assessed. Results. Intratumoral administration of GURSA1 produced dose-dependent antitumor effects on tumor growth and metastatic burden, but did not result in a statistically significant survival benefit. The strain reduced tumor engraftment, the overall metastasis score, and the incidence of hemorrhagic ascites, while also decreasing tumor mass and volume, with the strongest effects observed at a dose of 1 × 10⁶ CFU. Treatment increased platelet counts and reduced urea and ALT levels toward values observed in intact mice, without affecting anemia, neutrophilia, or changes in AST, alkaline phosphatase, glucose, and total protein levels. Conclusions. These findings demonstrate that GURSA1 attenuates partial reduction in primary tumor burden in vivo and support further investigation of this strain as a potential oncolytic agent. Full article

Background: Autoinflammatory bone disorders are rare, non-infectious inflammatory conditions that primarily involve the skeleton, most commonly presenting as chronic nonbacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO). Less frequently, they occur in the context of Mendelian syndromes such as Majeed syndrome, deficiency of the interleukin-1 receptor antagonist (DIRA), and pyogenic arthritis; pyoderma gangrenosum; and acne (PAPA) syndrome. Given the role of IL-1-driven innate immune dysregulation across these bone disorders, and the growing, though heterogeneous, clinical experience with IL-1 blockade, this review maps and critically appraises the available evidence on canakinumab in autoinflammatory bone disorders. Methods: We systematically searched PubMed and the Cochrane Library (English, inception–July 2025) and screened ClinicalTrials.gov. Eligible reports included any case reports/series describing canakinumab use in autoinflammatory bone disorders (CNO/CRMO, Majeed, DIRA, PAPA). Results: Six publications met the inclusion criteria (one case series, five case reports; 10 patients). Complete responses were reported in all three patients with Majeed syndrome and in two patients with sporadic CRMO associated with systemic features. Partial responses occurred in two additional sporadic CRMO cases, while no meaningful response was documented in DIRA. No interventional trials of canakinumab were identified on ClinicalTrials.gov for CNO/CRMO, Majeed, DIRA, or PAPA. Conclusions: Although the role of IL-1 in the pathogenesis of autoinflammatory bone disease provides a rationale for IL-1 blockade, evidence for canakinumab remains limited and heterogeneous, precluding definitive conclusions. Indicators of benefits appear most consistently in Majeed syndrome and in selected CRMO phenotypes. Full article

A Group A Streptococcus (GAS, Streptococcus pyogenes) is an exclusively human pathogen whose virulence is driven by a diverse array of surface structures, secreted toxins, and immune evasion mechanisms. Central to its pathogenicity is the M protein, a surface-anchored molecule that inhibits phagocytosis by interfering with complement deposition and binding host factors such as fibrinogen. GAS also secretes a wide range of toxins and enzymes that damage tissues and disrupt host defences. Streptolysin O and streptolysin S are potent cytolysins that lyse immune cells and contribute to tissue necrosis. Pyrogenic exotoxins (such as SpeA and SpeC) act as superantigens, triggering massive, dysregulated T cell activation and cytokine release, an underlying mechanism in streptococcal toxic shock syndrome. Additional factors like DNases and streptokinase facilitate bacterial spread by breaking down host tissue and counteracting neutrophil extracellular traps (NETs). Immune evasion is further supported by the production of enzymes that interfere with complement functions, like the cleavage of chemokines and the targeting of antibodies. Together, these virulence determinants allow GAS to cause a wide spectrum of diseases, ranging from uncomplicated pharyngitis and impetigo to invasive conditions like necrotising fasciitis and sepsis. This review provides a timely overview of the important GAS virulence factors and an update on the current vaccine landscape. Full article

Background/Objectives: Streptococcus pyogenes (Group A beta-hemolytic streptococcus, GAS) is the most common cause of bacterial pharyngitis and a major contributor to morbidity and mortality worldwide. There has been an increase in invasive GAS infections and related deaths in several European countries post-COVID-19 pandemic. We aimed to assess parental knowledge, attitudes, and practices regarding GAS pharyngotonsillitis, with a focus on antibiotic use and misuse. Methods: A cross-sectional questionnaire-based study was conducted on a convenience sample of parents of children admitted to the Pediatric Ward or visiting the Pediatric Emergency Department of the University General Hospital of Patras, Greece (September 2024–February 2025). For knowledge assessment, the questionnaire consisted of 10 True/False questions, based on which a total knowledge score was calculated. For attitude and practice assessment, the questionnaire consisted of 10 Likert scale questions. A Negative Practice Score was calculated as a sum of the answers in five practices with a negative perspective, with higher scores indicating worse practices and lower scores indicating better practices. Results: The study enrolled 378 parents, 79% of them were aware that not all children with a sore throat need antibiotics, and 61% believed asymptomatic children with a positive strep antigen test should receive antibiotics. Concerns about GAS transmissibility were high (76%), while attitudes about severity were mixed. A median GAS total knowledge score of 6 (IQR: 4–7) indicated moderate knowledge. Multivariable analysis revealed that male parents, non-immigrants, those previously hospitalized for GAS infection, and those informed by pediatricians or reliable websites had significantly higher knowledge scores. Regarding practices, most parents (72%) disagreed with requesting antibiotics from pediatricians, and 93.9% did not administer leftover antibiotics. Additionally, 58% expressed more concerns in recent years due to the increase in invasive infections. The median GAS Negative Practice Score was 10.5 (IQR: 7.0–13.0), indicating generally good practices, as lower scores correspond to fewer negative practices. Older parents and those with higher knowledge scores were also linked to fewer negative practices in multivariable analysis. Conclusions: These findings highlight the importance of targeted education on GAS pharyngotonsillitis and the need to focus on specific population groups to reduce antibiotic misuse. Full article

This study compares the chemical composition, antimicrobial effects, and antibiotic-potentiating capacity of three Lauraceae essential oils (EO): Cryptocarya agathophylla (CAEO), Litsea cubeba (LCEO), and Laurus nobilis (LNEO). Gas chromatography–mass spectrometry (GC–MS) analysis revealed distinct chemotypes: CAEO and LCEO were dominated by oxygenated monoterpenes, while LNEO contained the highest levels of monoterpene hydrocarbons. Antibacterial testing against nine bacterial strains showed strain-dependent growth suppression trends, while true minimum inhibitory concentrations (MICs) were reached only in selected cases. EO–ampicillin interactions were evaluated using MIC-based checkerboard criteria, whereas OD-derived inhibition parameters were used exclusively to describe sub-MIC potentiation trends. In combination assays, LNEO exhibited the most pronounced potentiating effects against Streptococcus pyogenes, Shigella flexneri, and Haemophilus influenzae, while CAEO and LCEO showed moderate or strain-dependent enhancement. Hierarchical clustering highlighted distinct oil- and strain-specific interaction profiles. Overall, although CAEO displayed stronger intrinsic antibacterial effects when tested alone, LNEO emerged as the most effective potentiator of ampicillin activity in a strain-dependent manner. The effects of the major compounds identified in the Lauraceae EO were assessed in silico against protein targets of some microorganisms using the AutoDock software version 4.2.6. The docking scores revealed binding affinities of the bioactive compounds towards Dpr protein (4.3–5.8 kcal/mol), DNA gyrase (4.7–7.1 kcal/mol), mono- diacylglycerol lipase (4.4–6.2 kcal/mol), CYP51 (5.8–8.0 kcal/mol), phage-encoded quorum sensing anti-activator (5.8–8.0 kcal/mol) and Chondroitin ABC lyase I (4.8–6.3 kcal/mol). Two (2) hit compounds (α-Citral, β-Citral) were finely defined by strong hydrophobic and hydrophilic interactions with the bacterial and fungal protein targets, respectively. Full article

Background/Objectives: The present study is aimed at evaluating the chemical profile and biological activity of the widespread species Oenothera biennis L. in Bulgaria, collected from its natural habitat. Methods: The seeds of the species were collected in 2023 and 2024, and the fatty acid and unsaponified (sterols, tocopherols, phospholipids) profile of the glyceride oil was investigated using standard chromatographic methods. The oil’s antimicrobial activity was evaluated using MBC/MFC assays, while its antioxidant capacity was assessed using the ORAC method. The proliferative effects of the oil were investigated using an MTT assay in human cell lines BJ, HaCaT, and MCF-12F. Results: The oil content of the seeds remained stable during the two years studied (16.7–16.9%). Variations were observed in the oil’s unsaponified fraction, including sterols, phospholipids, tocopherols, and several fatty acids. The primary fatty acid (linoleic acid) remained at almost the same value (~70%) during both periods, while γ-linolenic acid varied from 7.1% to 13.7%. β-sitosterol and phosphatidylcholine were the leading sterol and phospholipid components, while γ-tocopherol predominated among the tocopherols. The oil exhibited antimicrobial activity only against S. epidermidis and S. pyogenes and showed strong antioxidant capacity. MTT assays present sustained viability in BJ and MCF-12F cells and significantly increased proliferation in HaCaT cells. Conclusions: The oil demonstrated promising antioxidant potential, selective antimicrobial effects, and keratinocyte-stimulating activity, supporting its potential for diverse applications. However, to further confirm these findings, in vivo studies of the oil are needed. Full article

Background: Community-acquired pneumonia (CAP) in children may be complicated by necrotizing pneumonia (NP), complicated parapneumonic effusion (CPPE), and lung abscess. These complications prolong hospitalization and require medical and surgical intervention. Objectives. To describe clinical course, diagnostic workup, and management of cCAP (complicated CAP) in children admitted to the Women’s and Children’s Health Department, Padua University Hospital, between January 2022 and September 2024. To identify factors associated with disease severity and evaluate outcomes. Methods: All children hospitalized for cCAP during the study period were included. Data collected comprised clinical features, laboratory and imaging findings, medical and surgical management, and outcomes. Results: Forty patients (mean age 4.4 y; 13.15% of pneumonia admission) were included: 67.5% had NP with CPPE, 22.5% isolated effusion, 10% NP without effusion. All patients were febrile at onset, 62.2% had cough, 32.5% abdominal pain, 30% rhinitis. NP was confirmed by contrast-enhanced chest CT. Thirty patients (75%) had positive microbiological testing, mainly Streptococcus pneumoniae and Streptococcus pyogenes. 77.5% required oxygen therapy (five invasive ventilation and one with ECMO). Median fever duration 18 days (IQR 15–27) with elevated CRP (median peak 300 mg/L). Pleural drainage was performed in 66.7%, fibrinolytics in 17.5%, thoracoscopic decortication in 12.5%, and lobectomy in one patient. Radiological resolution occurred at a median of 31 days post-discharge, with normal pulmonary function at a median of 15 months. Conclusions: Despite pediatric cCAP severity, short- and long-term outcomes are favorable. Early recognition and integrated management are crucial, and further prospective studies are warranted to optimize care and identify severity predictors. Full article

A novel facultatively anaerobic, Gram-negative, curved rod-shaped bacterium was isolated from blood cultures obtained from a patient with pyogenic spondylitis in Japan. The organism was additionally detected by 16S rRNA gene sequence analysis in a formalin-fixed, paraffin-embedded lumbar spine biopsy specimen from the same patient. The type strain, designated THUN1379ᵀ, is motile by means of a single polar flagellum and forms circular, white to translucent colonies on R2A agar and 5% sheep blood agar. The strain is oxidase-positive and catalase-negative and grows at temperatures ranging from 25 to 42 °C. Phylogenetic analysis based on the 16S rRNA gene sequence placed strain THUN1379ᵀ within the genus Paludibacterium (family Chromobacteriaceae), showing the highest sequence similarity to Paludibacterium purpuratum KJ031ᵀ (98.6%). Whole-genome sequencing revealed a genome size of approximately 3.6 Mb with a DNA G+C content of 61.3 mol%. Phylogenomic analysis based on whole-genome sequences supported the distinct taxonomic position of strain THUN1379ᵀ within the genus. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain THUN1379ᵀ and Paludibacterium purpuratum KJ031ᵀ were 79.7% and 23.1%, respectively, which are well below the accepted thresholds for species delineation. On the basis of phenotypic, chemotaxonomic, and genomic characteristics, strain THUN1379ᵀ represents a novel species of the genus Paludibacterium, for which the name Paludibacterium flexuosum sp. nov. is proposed. The type strain is THUN1379ᵀ (=JCM 36560ᵀ = KCTC 8465ᵀ). Full article

Rosacea is a chronic inflammatory skin disorder characterized by oxidative stress, innate immune dysregulation, vascular instability, and microbiome-related triggers. Glycyrrhiza glabra (Gg, licorice) root contains phenolics and triterpenoids with antioxidant, anti-inflammatory, antimicrobial, and anti-angiogenic properties that may benefit rosacea-prone skin. Xanthan-gum hydrogels containing 2% methanolic Gg extract (S1, S2) were prepared and characterized. Rheology, in vitro release, and in vitro permeation were evaluated, with the aim of assessing their suitability as topical formulations for rosacea-prone skin. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Antimicrobial effects were tested against S. pyogenes, S. aureus, and C. acnes. Safety and bioactivity were examined through HaCaT keratinocyte assays (MTT, Neutral Red, LDH), the HET-CAM irritation test, and the CAM angiogenesis assay. Immunocytochemistry was performed on rosacea-related inflammatory markers. Both hydrogels showed suitable rheology, sustained release, and preserved strong antioxidant activity. Moderate antimicrobial effects were observed, particularly against S. pyogenes and C. acnes. HaCaT cell viability remained above 84% for the S2 formulation at the highest concentration (200 µg/mL), indicating improved cytocompatibility compared with formulation S1. The hydrogels were non-irritant in the HET-CAM model and reduced neovascularization in the CAM assay, with a more sustained effect observed for formulation S2. Immunohistochemistry supported potential modulation of inflammatory pathways relevant to rosacea, evidencing suppressed VEGF expression and preserved CD44-mediated integrity, particularly in the Labrasol-based formulation (S2), while Caspase-3 staining indicated a controlled apoptotic profile. Overall, Gg hydrogels are safe, biocompatible, non-irritant, and exhibit antioxidant, antimicrobial, and anti-angiogenic activities, supporting their potential as biocompatible topical formulations with antioxidant and pathway-modulating properties relevant to the biological features associated with rosacea, while underscoring the importance of formulation design. Full article

This study investigated the phytochemical composition and biological activity of Cymbopogon citratus microshoot cultures and evaluated their suitability for incorporation into a cosmetic formulation. Microshoot cultures were established on Murashige and Skoog media supplemented with plant growth regulators and served as a reproducible source of biomass. Methanolic and ethanolic extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Chemical composition was characterized using LC-MS/MS analysis, which revealed the presence of phenolic acids and flavonoids, with p-coumaric, caffeic, and ferulic acids being among the most abundant detected constituents. In biological assays, the extracts inhibited murine tyrosinase in a concentration-dependent manner and exhibited antimicrobial activity against selected oral and skin-associated microorganisms, including Streptococcus mutans, Streptococcus pyogenes, and Staphylococcus epidermidis, as well as showing fungistatic and fungicidal effects against Candida albicans. Cytotoxicity analysis performed on HaCaT keratinocytes confirmed biocompatibility within the tested concentration range. To assess formulation suitability, the microshoot extract was incorporated into an oil-in-water (O/W) cream, which maintained stable pH, viscosity, and physical properties while preserving the antioxidant activity of the extract. Overall, these findings indicate that C. citratus microshoot cultures represent a reproducible source of bioactive metabolites with potential application in cosmetic formulations. Full article