Search Results (4,508)

Extracellular traps (ETs) are immune-derived chromatin networks initially described as antimicrobial barriers but increasingly recognized as modulators of tissue homeostasis and autoimmunity. The oral mucosa, constantly exposed to inflammatory stimuli, is particularly sensitive to ET-mediated remodeling (extracellular traps-mediated remodeling). In this study, we investigated how platelet-rich plasma (PRP), platelet-poor plasma (PPP), and washed platelets (WPT), widely used in regenerative medicine, influence ETosis in monocytes and macrophages, and how these ETs modulate the responses of primary buccal keratinocytes (pBMKs). ETs were induced in monocytes/macrophages using PRP, PPP, and WPT. pBMKs were exposed to ET-rich supernatants, and proliferation was monitored in real time through a live cell imaging system. ETs derived from PRP, PPP, and WPT did not induce either a statistically significant proliferation or morphological changes in buccal keratinocytes. These findings suggest that both platelet-derived products (PRP, PPP, WPT) and ETs play a crucial role in modulating epithelial biology, thus suggesting their possible role in chronic autoimmune diseases characterized by persistent inflammation and epithelial remodeling. Full article

Oral candidiasis (OC) is the most frequent fungal infection among users of dental prosthetic devices, immunocompromised patients, and those who underwent chemotherapy treatment and had a complication of long-term antibiotic therapy. About 150 species of Candida fungi have been described, whereas over 80% of oral fungal infections are attributed to the opportunistic pathogen Candida albicans. Pain, dryness of oral mucosa, pathological lesions, and intermittent mucosal bleeding are the main symptoms that worsen the daily functioning of the abovementioned fungal-infected patients. A promising adjunctive strategy may involve the use of probiotic bacteria to attenuate fungal colonization in the oral cavity in order to reduce the need for conventional treatment, which carries a risk of antifungal drug resistance—a significant problem worldwide. Probiotic formulations mostly incorporate commensal bacteria that naturally inhabit oral ecosystems such as Lactobacillus spp., Bifidobacterium spp., Bacillus spp., and others. Probiotic organisms may contribute to the restoration of oral microbiome homeostasis through numerous mechanisms, such as competitive control of Candida species numbers, better adhesion to oral mucosa and production of bioactive compounds and antimicrobial metabolites. Despite many studies, the current evidence base remains heterogeneous. Well-designed studies across diverse populations are required to determine whether probiotic-based interventions can be an effective and clinically useful alternative or adjunct to standard antifungal therapy of OC. Full article

Background/Objectives: Calcium–phosphorus metabolism is critical for skeletal development in weaned piglets. This study evaluated the effects of dietary 25-hydroxyvitamin D₃ (25-OH-VD₃) in combination with phytase and probiotics on mineral metabolism, bone development, and related molecular mechanisms in weaned piglets. Methods: Sixty 28-day-old weaned piglets (7.1 ± 1.30 kg) were randomly assigned to four dietary treatments for 31 days (including 3 days of acclimation): CON (basal diet + 50 µg/kg 25-OH-VD₃), HI (CON + 50 mg/kg phytase), CY (CON +10 mg/kg probiotics), HICY (CON + 50 mg/kg phytase + 10 mg/kg probiotics). Apparent calcium digestibility, serum biochemical indices, bone mineral density (BMD), and mRNA and protein expression of calcium–phosphorus transport- and metabolism-related genes in jejunal mucosa and kidney were assessed. Results: Compared with CON, piglets in the HI, CY, and HICY groups showed higher apparent calcium digestibility (p < 0.05). Serum transforming growth factor-β was elevated in CY and HICY (p < 0.05). HI enhanced metatarsal and toe BMD (p < 0.05) and upregulated jejunal solute carrier family 34, member 2 (SLC34A2) and SLC34A3 mRNA expression (p < 0.05). In contrast, HICY reduced mRNA expression of transient receptor potential cation channel subfamily V member 6 and calcium-binding protein D28k, as well as of calcium-binding protein D9k and cytochrome P450 27B1 in the kidney (p < 0.05). Renal calcium-sensing receptor protein abundance increased in CY (p < 0.05). Conclusions: Supplementation of 25-OH-VD₃ with phytase and/or probiotics improved calcium utilization and modulated key transport pathways, contributing to enhanced bone development in weaned piglets. These findings highlight coordinated nutritional regulation of mineral metabolism during early post-weaning growth. Full article

The mammalian intestinal epithelium is a rapid self-renewal tissue in the body, serving as a critical interface between the host and the external environment. Maintaining the intestinal epithelium homeostasis requires precise coordination of cellular processes, including proliferation, migration, differentiation, autophagy, and cell-to-cell interaction. An increasing body of evidence has unveiled circular RNAs (circRNAs) as abundant and stable regulatory molecules that play pivotal roles in the intestinal epithelial biology and are intimately involved in many aspects of gut mucosal pathologies. Unlike linear RNAs, circRNAs form covalently closed loop structures through back-splicing events, conferring remarkable stability and resistance to exonucleolytic degradation. circRNAs regulate the growth of the intestinal mucosa, injury-induced epithelial regeneration, and gut barrier function via diverse mechanisms, including interactions with microRNAs and RNA-binding proteins. Deregulated circRNAs are implicated in the pathogenesis of various gut mucosal disorders such as inflammatory bowel disease and malignancies. In this review, we highlight pathobiological functions and mechanisms of intestinal epithelium-enriched circRNAs, particularly circHIPK3, Cdrlas, and circPABPN1, in the epithelium homeostasis and pathologies and also discuss potential clinical application of circRNAs as diagnostic biomarkers and therapeutic targets in patients with critical diseases. Full article

Background/Objectives: The emergence of SARS-CoV-2 variants and breakthrough infections underscores the need for next-generation vaccines capable of protecting from natural infection and/or preventing virus transmission. Intranasal vaccination offers a promising approach by eliciting local immune responses in the nasal mucosa, the primary site of infection and reservoir for transmissible virus. We evaluated two live-attenuated, respiratory syncytial virus-vectored vaccines in which the RSV F and G surface glycoproteins were replaced with a chimeric SARS-CoV-2 Spike protein from the ancestral USA/WA-1/2020 strain (MV-014-212) or the Delta variant (MV-014-212-delta). Methods: K18-hACE2 mice and LVG Syrian hamsters were vaccinated with a single intranasal dose of MV-014-212 or MV-014-212-delta. Systemic and mucosal immunity were assessed following vaccination, and protection was evaluated following Delta SARS-CoV-2 challenge. In vaccinated hamsters, morbidity, viral shedding, and lung inflammation and injury were also assessed following natural exposure to infected cagemates. Results: A single intranasal dose of either vaccine elicited systemic and mucosal immunity in K18-hACE2 mice, including serum neutralizing antibodies, Spike-specific memory B cells and plasmablasts, and Spike-specific CD8⁺ lung-resident memory T cells. Although MV-014-212-delta vaccination provided the best protection against the Delta variant virus challenge, both vaccines decreased viral loads in nasal discharge, lung, and brain, and reduced weight loss and mortality. In naturally acquired infection studies, vaccinated hamsters exposed to infected cagemates exhibited minimal weight loss, limited viral replication within the nasal mucosa, and attenuated lung pathology. Conclusions: Intranasal RSV-vectored vaccines can elicit broad protective respiratory immunity, suggesting that this platform could be leveraged for other respiratory pathogens. Full article

The rectal mucosa houses a large number of viruses with important roles in shaping the local microbial communities and modulating immune responses, which could influence host susceptibility to infection and other diseases. Unique composition of the gut microbiome, including the predominance of clinically significant eukaryotic viruses like herpesviruses, cytomegalovirus, and human papillomavirus, has been described in both people with HIV (PWH) and men who have sex with men (MSM) vulnerable to HIV. Despite these insights, the rectal virome and the clinical implications of virome–bacteriome–immune interactions in the rectal mucosa remain poorly understood. In this review, we synthesize existing data on the composition of the rectal virome, its interactions with the bacteriome and the immune system, and implications on clinical outcomes in people living with or vulnerable to HIV. We also highlight the gaps and research needed to further explore and unravel these relationships. Full article

Ulcerative colitis (UC) is a type of inflammatory bowel disease without curative therapeutics. Recent studies demonstrate that Akkermansia muciniphila exerts mitigating effects on UC, but the underlying mechanisms remain unclear. In this study, we isolated a strain of A. muciniphila, designated NND9, from the feces of DSS-induced ulcerative colitis model mice and investigated its effects on UC of the mouse model. NND9 significantly alleviated UC severity in the mice by restoring gut barrier integrity through improving colonic mucus layer thickness, mitigating goblet cell depletion, and halting epithelial cell death. Mechanistically, NND9 suppressed the expression of the Tnfrsf10b gene encoding death receptor 5 (DR5) on the surface of colonic epithelial cells. Additionally, NND9 inhibited the phosphorylation of kinase 3 (RIPK3) and the pseudokinase mixed-lineage kinase domain-like protein (MLKL) associated with the necrotic apoptosis pathway, thereby reducing gut epithelial cell death. NND9 also markedly ameliorated the gut microbiome of the colitis mice. Untargeted metabolomics analysis demonstrated that NND9 modulated both tryptophan and bile acid metabolism. In conclusion, NND9 exhibits curative effects on UC by resolving inflammatory reactions of the gut mucosa through the DR5-RIPK3/p-RIPK3-MLKL/p-MLKL pathway and redressing gut dysbiosis. This study provides valuable information for the development of innovative therapeutic strategies for the treatment of UC. Full article

Candida albicans is a yeast found in the oral cavity, gastrointestinal tract, and vaginal mucosa. This species is the most prevalent and virulent in conditions such as oral candidiasis. Myrtenol is a bicyclic monoterpene alcohol recognized for its antioxidant and anti-inflammatory attributes. Its primary source is the essential oil extracted from plants of the Myrtaceae family. This study evaluated the effect of (−)-myrtenol on the virulence factors of Candida albicans. Ten clinical isolates of Candida albicans and one reference strain (ATCC 90028) were used in this study. The virulence factors examined included adhesion, morphogenesis, and lipase production. Assays were conducted in the presence and absence of (−)-myrtenol, using a concentration corresponding to the minimum inhibitory concentration (MIC; 256 µg/mL). Results: The compound reduced the adherence of C. albicans to human oral epithelial cells (92.24 vs. 28.69), and reduced filamentation in liquid (3.17 vs. 2.57) and solid media. Furthermore, (−)-myrtenol inhibited lipase activity (0.68 vs. 1.00). Virulence factors expressed by C. albicans contribute to increased infection rates and, consequently, increased morbidity and mortality. The present findings demonstrate that (−)-myrtenol affects virulence-associated phenotypes of C. albicans in vitro. This compound represents a promising candidate for further investigation, particularly in studies addressing its mechanisms of action, safety, and potential applicability. Full article

Background: Early detection of oral potentially malignant disorders (OPMDs) and early-stage oral squamous cell carcinoma (OSCC) remains a major clinical challenge, as initial lesions often present with subtle or nonspecific findings during conventional white-light examination. Narrow-band imaging (NBI) enhances visualization of mucosal microvasculature and may improve the identification of dysplastic and malignant transformation. Methods: A narrative review of the literature was conducted in the PubMed, Scopus and Google Scholar databases. Studies published between January 2012 and January 2025 evaluating clinical applications of NBI in oral mucosal lesions, OPMDs, or OSCC were included. Results: NBI enhances visualization of intraepithelial papillary capillary loops (IPCLs), whose morphological alterations correlate with epithelial dysplasia and malignant transformation. Evidence suggests high diagnostic sensitivity (up to 87–100%) and specificity (approximately 83–96%) for detecting high-grade dysplasia and early OSCC. NBI also improves biopsy site selection, reduces sampling error, and supports surveillance of high-risk patients. Conclusions: NBI represents a valuable adjunctive diagnostic tool in oral medicine and dentistry. Although it does not replace histopathological examination, its integration into clinical assessment may enhance early cancer detection and improve management of patients with OPMDs. Full article

Background/Objectives: Peri-implant inflammatory complications remain a major cause of late implant failure and are closely associated with the condition of peri-implant soft tissues. Insufficient keratinized attached mucosa has been identified as a potential risk factor for peri-implant inflammation; however, morphological and immunohistochemical validation of soft tissue remodeling following corrective interventions remains limited. The aim of this study was to perform a morphological and immunohistochemical evaluation of a reproducible surgical approach for increasing keratinized attached mucosa around dental implants. Methods: A comparative clinical–morphological study included 25 patients undergoing implant-supported prosthetic treatment. Patients were divided into a control group (standard prosthetic protocol without soft tissue augmentation, n = 10) and a study group (soft tissue correction using a previously developed technique, n = 15). Punch biopsies of peri-implant mucosa were obtained at baseline and prior to definitive prosthetic restoration. Histological examination and immunohistochemical analysis were performed using the semi-quantitative Astaldi–Verga method. Expression of inflammatory markers (MPO, CD3, CD20, CD68), vascular marker CD31, and remodeling markers MMP-9 and TIMP-2 was evaluated. Data were analyzed using the Mann–Whitney U test (p < 0.05). Results: The study group demonstrated significantly lower expression of inflammatory markers, including MPO, CD68, CD3, and CD20 (p < 0.001), and reduced MMP-9 expression (p = 0.001) compared with controls. The MMP-9/TIMP-2 balance was more favorable in the study group, suggesting more regulated extracellular matrix remodeling. Histologically, the control group exhibited epithelial disruption and microcirculatory alterations, whereas the study group showed preserved epithelial architecture and reduced inflammatory infiltration. Conclusions: Morphological and immunohistochemical assessment suggests that soft tissue correction of keratinized mucosa deficiency may be associated with more favorable early peri-implant soft tissue characteristics, including reduced inflammatory activity and modulation of matrix remodeling. Immunohistochemical markers such as MMP-9 and TIMP-2 may provide additional insight into early soft tissue integration around dental implants. However, these findings should be interpreted with caution due to the exploratory design and short follow-up period. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Emerging evidence highlights the role of the gut microbiota in the development and progression of CRC. Microbial dysbiosis is hypothesized to contribute to chronic inflammation through a variety of mechanisms, such as the production of free radicals, which induce mutagenesis and immune dysregulation in the host, ultimately leading to diseases such as cancer. Methods: Tumor tissue samples or healthy mucosa tissue were collected for bacterial DNA extraction. The V3–V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Bioinformatics analysis was performed with QIIME2, including quality control, DADA2 denoising, alpha and beta diversity calculation, and taxonomic classification using the SILVA database. Results: Differences in microbial composition were observed between groups. The healthy controls exhibited high relative abundances of beneficial genera such as Faecalibacterium, Bacteroides, and Asteroleplasma, whereas the patients with CRC showed enrichment of atypical genera including Novosphingobium, Bradyrhizobium, and Undibacterium. Alpha diversity was lower in the CRC group, and clear clustering by group was observed in the beta diversity analysis. LEfSe analysis identified potential bacterial biomarkers associated with CRC at both the species and genus levels. Conclusions: The findings of this study support the hypothesis that colorectal cancer is associated with distinct alterations in gut microbiota composition, such as an increase in the Novosphingobium genus and a decrease in the Bacteroides genus. An exploratory description of these microbial profiles may aid in the development of microbiome-based diagnostic and therapeutic strategies and contribute to current knowledge of the role of the gut microbiota in CRC in southern Peru. Full article

Background: Preparing patients for oncological therapy requires the elimination of foci of infection in accordance with Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) guidelines. Complications of dental caries, such as abscesses, can lead to sepsis. In Poland, the pre-oncologic dental treatment of patients with hematopoietic disorders does not yet meet MASCC/ISOO standards; however, an inventory of the current status of dental care for these patients is ongoing. The aim of this study was to investigate the frequency of dental caries and to define the local caries risk factors in adult patients prior to Hematopoietic Stem Cell Transplantation (HSCT) as a part of anticancer therapy. Additionally, the time available for dental treatment was assessed. Methods: A total of 302 patients were examined. Dental status was determined based on the number of decayed, missing and filled teeth and on treatment needs. Local caries risk factors, such as poor dietary habits, insufficient oral hygiene, and symptoms of reduced salivary flow, were examined. The diet was assessed using a questionnaire; tooth cleaning efficiency was assessed as a percentage of dental surfaces with biofilm. Symptoms of reduced salivary flow were determined by subjective and clinical signs of low salivary secretion. Results: Active (progressive) dental caries was diagnosed in 85.2% of patients. Insufficient oral hygiene had been found in 71.52% of those examined. Symptoms of hyposalivation were present in 85% of patients. In 31% of cases, time available for dental treatment prior to HSCT was too short. Conclusions: Tooth decay, the presence of caries risk factors, and insufficient time for oral treatment in patients submitted to HSCT represent a serious clinical problem. There is a clear need to establish comprehensive oral health protocols aimed at providing patients with appropriate, urgent dental care. Furthermore, coordination between oncologists and dentists in Poland must be improved. Currently patients are rarely referred to a dentist before starting anticancer therapy; those scheduled to hematopoietic stem cell transplantation, usually see a dentist too late. Full article

Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease, are chronic inflammatory disorders of the gastrointestinal tract associated with epithelial barrier dysfunction, dysregulated immune responses, and an increased risk of cancer. Persistent inflammation is a key driver of IBD-associated tumorigenesis, yet the transcriptional regulators linking inflammatory signaling to epithelial transformation remain incompletely defined. FOSL1 (FOS-like antigen 1), a member of the activator protein-1 (AP-1) transcription factor family, has emerged as a critical mediator at the intersection of inflammation, epithelial homeostasis, and cancer progression. FOSL1 is induced by pro-inflammatory pathways commonly activated in IBD, including MAPK/ERK, NF-κB, and cytokine signaling, and regulates gene programs involved in cell proliferation, migration, barrier integrity, immune modulation, and survival. Accumulating evidence demonstrates that FOSL1 expression is elevated in inflamed intestinal mucosa and in IBD-associated malignancies, where it contributes to epithelial dysfunction, chronic inflammation, tumor initiation, metastasis, angiogenesis, and therapeutic resistance. Moreover, FOSL1-driven transcriptional networks show mechanistic overlap between IBD-associated colorectal cancer (CRC) and other inflammation-linked gastrointestinal cancers, such as pancreatic ductal adenocarcinoma (PDAC). In this review, we summarize current knowledge on the regulation and function of FOSL1 in intestinal inflammation and IBD-associated cancers, highlight its context-dependent roles in epithelial and immune compartments, and discuss emerging therapeutic strategies aimed at indirectly targeting FOSL1 signaling pathways. Full article

Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis vaccines that contribute to ongoing transmission. A narrative review of the literature was conducted, focusing on mechanisms of host–pathogen interaction, immune evasion, and vaccine-induced immunity. Evidence indicates that although acellular vaccines effectively reduce disease severity, they fail to prevent nasopharyngeal colonization and transmission, largely due to insufficient induction of mucosal immunity, T helper 1 (Th1) and T helper 17 (Th17) responses, and airway tissue-resident memory T cells. In contrast, natural infection induces broader immune responses, including secretory IgA production and robust cellular immunity, which are associated with improved bacterial clearance. Emerging next-generation vaccine strategies, including mucosal, outer membrane vesicle-based, and live-attenuated platforms, demonstrate enhanced ability to reduce bacterial colonization in preclinical and clinical models. In conclusion, effective control of pertussis transmission will require vaccine approaches that replicate infection-induced immunity at the respiratory mucosa, emphasizing the need for redesigned immunization strategies. Full article

Background/Objectives: Rebamipide is a gastroprotective agent with poor aqueous solubility and rapid gastrointestinal clearance, leading to reduced therapeutic efficiency. This study aimed to enhance the solubility, mucoadhesion, and sustained oral delivery of Rebamipide through the development of a deep eutectic mixture (DEM)-based bioadhesive controlled-release granule formulation. Methods: In silico hydrogen-bonding interactions between Rebamipide, malonic acid, and urea were analyzed using CCDC tools. A thermodynamically stable DEM (1:3:1) was prepared and incorporated into bioadhesive granules using chitosan and HPMC. Physicochemical characterization was conducted using FTIR, DSC, TGA, and PXRD. Solubility, in vitro dissolution, ex vivo mucoadhesion (sheep gastric mucosa), and in vivo gastric retention (BaSO₄-loaded granules in rats) were evaluated. Results: The optimized DEM significantly enhanced Rebamipide solubility (10.08 mg/mL vs. 0.045 mg/mL). Solid-state analyses confirmed hydrogen-bond formation and reduced crystallinity. DEM granules exhibited sustained drug release over 24 h (99.7 ± 0.8%) with improved dissolution efficiency compared to the marketed tablet (Mucosta®, 100 mg; T₅₀%: 5.03 h vs. 0.82 h). Kinetic modeling indicated non-Fickian anomalous transport (n = 0.47). The bioadhesive force of DEM granules (0.29 ± 0.02 N) was significantly higher than that of the pure drug and physical mixture. In vivo radiographic studies confirmed prolonged gastric retention. Conclusions: The DEM-based bioadhesive granule system effectively improves solubility, dissolution rate, mucoadhesion, and gastric retention of Rebamipide. This approach represents a promising platform for once-daily gastroretentive oral delivery, pending further pharmacokinetic evaluation. Full article