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Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab's currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. An evaluation revealed surrogate characteristics that were satisfactory and exhibited good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team's original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners. [ABSTRACT FROM AUTHOR]

Summary: Despite the widespread adoption of nasal endoscopy (NE) in the evaluation of sinonasal disease, its diagnostic potential may still be underutilized. Developments in endoscopic technology have led to significant improvements in video quality and maneuverability. However, there is concern that NE continues to be used primarily for the identification of gross pathology, with relative neglect of more subtle findings such as surface features of inflammation and mucus. With fewer technical limitations to perceive these abnormalities, there is potential to greatly improve the diagnostic value of NE. The reader is herein asked to consider several important visual nuances encountered during NE, with the hope that this engenders an appreciation of the versatility of NE as a diagnostic tool. [ABSTRACT FROM AUTHOR]

Background While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation. Methods We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0–5 days after symptom onset) or late (6–20 days after symptom onset) phase. Results Patients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-γ, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease. Conclusions Defective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19. [ABSTRACT FROM AUTHOR]

We aimed to investigate the expression and motor modulatory roles of several mechano-sensitive channels (MSCs) in human ureter. Human proximal ureters were obtained from eighty patients subjected to nephrectomy. Expression of MSCs at mRNA, protein and functional levels were examined. Contractions of longitudinal ureter strips were recorded in organ bath. A fluorescent probe Diaminofluoresceins was used to measure nitric oxide (NO). RT-PCR analyses revealed predominant expression of Piezo1 and TRPV2 mRNA in intact ureter and mucosa. Immunofluorescence assays indicate proteins of MSCs (Piezo1/Piezo2, TRPV2 and TRPV4) were mainly distributed in the urothelium. Ca2+ imaging confirmed functional expression of TRPV2, TRPV4 and Piezo1 in cultured urothelial cells. Specific agonists of Piezo1 (Yoda1, 3–300 μM) and TRPV2 (cannabidiol, 3–300 μM) attenuated the frequency of ureteral contractions in a dose-dependent manner while the TRPV4 agonist GSK1016790A (100 nM–1 μM) exerted no effect. The inhibitory effects of Piezo1 and TRPV2 agonists were significantly blocked by the selective antagonists (Dooku 1 for Piezo1, Tranilast for TRPV2), removal of the mucosa, and pretreatment with NO synthase inhibitor L-NAME (10 μM). Yoda1 (30 μM) and cannabidiol (50 μM) increased production of NO in cultured urothelial cells. Our results suggest that activation of Piezo1 or TRPV2 evokes NO production and release from mucosa that may mediate mechanical stimulus-induced reduction of ureter contractions. Our findings support the idea that targeting Piezo1 and TRPV2 channels may be a promising pharmacological strategy for ureter stone passage or colic pain relief. [ABSTRACT FROM AUTHOR]

Antibodies, and notably immunoglobulins A (IgA), are paramount in mucosal tissues as protective immune effectors against invading pathogens and immunomodulators of the microbiota. Upon human immunodeficiency virus type 1 (HIV-1) infection, systemic and mucosal IgA antibody responses are triggered. While naturally produced serum HIV-1 envelope protein-specific IgA are quantitatively and qualitatively weaker than their IgG counterparts, they also possess antiviral properties including neutralization and Fc-dependent functions. IgA neutralizers can block HIV-1 mucosal transmission in animal models, indicating that their elicitation by vaccination would be an important component for preventing infection. Moreover, the first genuine IgA broadly HIV-1 neutralizing antibodies (bNAbs) were recently identified in certain individuals living with HIV-1. Vaccine-based induction of IgA bNAbs potentially protective at the mucosal level is therefore conceivable. Hence, research efforts must therefore be undertaken to better understand their development and functions. In this review, we present the general functions of IgA in homeostasis and antimicrobial immunity and discuss their involvement in the antibody responses against HIV-1. [ABSTRACT FROM AUTHOR]

Background and Aims This study aimed to identify microbial drivers of inflammatory bowel disease [IBD], by investigating mucosal-associated bacteria and their detrimental products in IBD patients. Methods We directly cultured bacterial communities from mucosal biopsies from paediatric gastrointestinal patients and examined for pathogenicity-associated traits. Upon identifying Clostridium perfringens as toxigenic bacteria present in mucosal biopsies, we isolated strains and further characterized toxicity and prevalence. Results Mucosal biopsy microbial composition differed from corresponding stool samples. C. perfringens was present in eight of nine patients' mucosal biopsies, correlating with haemolytic activity, but was not present in all corresponding stool samples. Large IBD datasets showed higher C. perfringens prevalence in stool samples of IBD adults [18.7–27.1%] versus healthy controls [5.1%]. In vitro , C. perfringens supernatants were toxic to cell types beneath the intestinal epithelial barrier, including endothelial cells, neuroblasts, and neutrophils, while the impact on epithelial cells was less pronounced, suggesting C. perfringens may be particularly damaging when barrier integrity is compromised. Further characterization using purified toxins and genetic insertion mutants confirmed perfringolysin O [PFO] toxin was sufficient for toxicity. Toxin RNA signatures were found in the original patient biopsies by PCR, suggesting intestinal production. C. perfringens supernatants also induced activation of neuroblast and dorsal root ganglion neurons in vitro , suggesting C. perfringens in inflamed mucosal tissue may directly contribute to abdominal pain, a frequent IBD symptom. Conclusions Gastrointestinal carriage of certain toxigenic C. perfringens may have an important pathogenic impact on IBD patients. These findings support routine monitoring of C. perfringens and PFO toxins and potential treatment in patients. [ABSTRACT FROM AUTHOR]

Organogenesis occurs in the uterus under low oxygen levels (4%). Preterm birth exposes immature newborns to a hyperoxic environment, which can induce a massive production of reactive oxygen species and potentially affect organ development, leading to diseases such as necrotizing enterocolitis. The β3-adrenoreceptor (β3-AR) has an oxygen-dependent regulatory mechanism, and its activation exerts an antioxidant effect. To test the hypothesis that β3-AR could protect postnatal ileal development from the negative impact of high oxygen levels, Sprague–Dawley rat pups were raised under normoxia (21%) or hyperoxia (85%) for the first 2 weeks after birth and treated or not with BRL37344, a selective β3-AR agonist, at 1, 3, or 6 mg/kg. Hyperoxia alters ileal mucosal morphology, leading to increased cell lipid oxidation byproducts, reduced presence of β3-AR-positive resident cells, decreased junctional protein expression, disrupted brush border, mucin over-production, and impaired vascularization. Treatment with 3 mg/kg of BRL37344 prevented these alterations, although not completely, while the lower 1 mg/kg dose was ineffective, and the higher 6 mg/kg dose was toxic. Our findings indicate the potential of β3-AR agonism as a new therapeutic approach to counteract the hyperoxia-induced ileal alterations and, more generally, the disorders of prematurity related to supra-physiologic oxygen exposure. [ABSTRACT FROM AUTHOR]

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. Thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and T-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

The process of development, recurrence, and exacerbation of the inflammatory process depends on the cytokine levels in IBD. For that reason, many cytokine therapies have been developed for treating IBD patients. Researchers employ various techniques and methodologies for cytokine profiling to identify cytokine signatures in inflamed mucosa. These include enzyme-linked immunosorbent assays (ELISA), multiplex immunoassays, flow cytometry, and gene expression analysis techniques (i.e., microarray, RNA-seq, single-cell RNA-seq (scRNA-seq), mass cytometry (CyTOF), Luminex). Research knowledge so far can give us some insights into the cytokine milieu associated with mucosal inflammation by quantifying cytokine levels in mucosal tissues or biological fluids such as serum or stool. The review is aimed at presenting state-of-the-art techniques for cytokine profiling and the various biomarkers for follow-up and treatment.

Abstract Background To elucidate the mechanism of dysfunction of tolerogenic dendritic cells (DCs) is of significance. Telomerase involves the regulation of the cell fate and activities. The objective of this study is to investigate the role of telomerase reverse transcriptase (TERT) in regulating the tolerogenic feature of DCs. Methods The telomerase was assessed in DCs, which were collected from patients with allergic rhinitis (AR), healthy control (HC) subjects, and mice. RNAs were extracted from DCs, and analyzed by RNA sequencing (RNAseq), real-time quantitative RT-PCR, and Western blotting. Results The results showed that expression of TERT was higher in peripheral DCs of AR patients. The expression of IL10 in DCs was negatively correlated with the levels of TERT expression. Importantly, the levels of TERT mRNA in DCs were associated with the AR response in patients with AR. Endoplasmic reticulum (ER) stress promoted the expression of Tert in DCs. Sensitization with the ovalbumin-aluminum hydroxide protocol increased the expression of Tert in DCs by exacerbating ER stress. TERT interacting with c-Maf (the transcription factor of IL-10) inducing protein (CMIP) in DCs resulted in CMIP ubiquitination and degradation, and thus, suppressed the production of IL-10. Inhibition of Tert in DCs mitigated experimental AR. Conclusions Elevated amounts of TERT were detected in DCs of patients with AR. The tolerogenic feature of DCs was impacted by TERT. Inhibited TERT attenuated experimental AR.

Abstract Background The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. Conclusions This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites.

Purpose: Little information is known about the mentalis nerve course from the lower lip approximation margin (free margin) to the upper lip. Likewise, no difference in nerve distribution has been observed between the cutaneous and mucosal parts of the lip. Therefore, this study reexamined mentalis nerve morphology. Methods: For macroscopic observations, three fresh cadavers were dissected (one male and two females; aged 78–93). We also evaluated histological sections obtained from five donated elderly cadavers (two males and three females, aged 82–96 years) and 15 human fetuses (11–40 weeks or crown–rump length 80–372 mm). Immunohistochemical analysis for S100 protein and tyrosine hydroxylase was performed. Results: In both fetuses and adult cadavers, one to three nerve branches ran upward in the submucosal tissue from the mental foramen. Near the free margin of the lip, some branches passed through the orbicularis oris muscle layer toward the lip skin, whereas others followed a reversed J-shaped course along the free margin. Nerve twigs ran in parallel beneath the mucosa, whereas wavy nerve twigs attached to the basal lamina of the lip epidermis. The difference in nerve endings abruptly occurred at the skin–mucosal junction. Tyrosine hydroxylase-positive sympathetic nerve twigs surrounded arteries and formed a branch composed of S100-negative unmyelinated fibers. Conclusion: The lower lip skin was innervated by a perforating branch passing through the orbicularis oris muscle, that was different from the lip mucosa. A sudden change in the nerve ending configuration at the mucocutaneous junction seemed to develop postnatally. [ABSTRACT FROM AUTHOR]

The process of development, recurrence, and exacerbation of the inflammatory process depends on the cytokine levels in IBD. For that reason, many cytokine therapies have been developed for treating IBD patients. Researchers employ various techniques and methodologies for cytokine profiling to identify cytokine signatures in inflamed mucosa. These include enzyme-linked immunosorbent assays (ELISA), multiplex immunoassays, flow cytometry, and gene expression analysis techniques (i.e., microarray, RNA-seq, single-cell RNA-seq (scRNA-seq), mass cytometry (CyTOF), Luminex). Research knowledge so far can give us some insights into the cytokine milieu associated with mucosal inflammation by quantifying cytokine levels in mucosal tissues or biological fluids such as serum or stool. The review is aimed at presenting state-of-the-art techniques for cytokine profiling and the various biomarkers for follow-up and treatment. [ABSTRACT FROM AUTHOR]

Purpose of review Disruption of the precious ecosystem of micro-organisms that reside in the gut - the gut microbiota - is rapidly emerging as a key driver of the adverse side effects/toxicities caused by numerous anti-cancer agents. Although the contribution of the gut microbiota to these toxicities is understood with ever increasing precision, the cause of microbial disruption (dysbiosis) remains poorly understood. Here, we discuss current evidence on the cause(s) of dysbiosis after cancer therapy, positioning breakdown of the intestinal mucosa (mucositis) as a central cause. Recent findings Dysbiosis in people with cancer has historically been attributed to extensive antibiotic use. However, evidence now suggests that certain antibiotics have minimal impacts on the microbiota. Indeed, recent evidence shows that the type of cancer therapy predicts microbiota composition independently of antibiotics. Given most anti-cancer drugs have modest effects on microbes directly, this suggests that their impact on the gut microenvironment, in particular the mucosa, which is highly vulnerable to cytotoxicity, is a likely cause of dysbiosis. Here, we outline evidence that support this hypothesis, and discuss the associated clinical implications/opportunities. Summary The concept that mucositis dictates microbiota compositions provides two important implications for clinical practice. Firstly, it reiterates the importance of prioritising the development of novel mucoprotectants that preserve mucosal integrity, and indirectly support microbial stability. Secondly, it provides an opportunity to identify dysbiotic events and associated consequences using readily accessible, minimally invasive biomarkers of mucositis such as plasma citrulline. [ABSTRACT FROM AUTHOR]

Background: To elucidate the mechanism of dysfunction of tolerogenic dendritic cells (DCs) is of significance. Telomerase involves the regulation of the cell fate and activities. The objective of this study is to investigate the role of telomerase reverse transcriptase (TERT) in regulating the tolerogenic feature of DCs. Methods: The telomerase was assessed in DCs, which were collected from patients with allergic rhinitis (AR), healthy control (HC) subjects, and mice. RNAs were extracted from DCs, and analyzed by RNA sequencing (RNAseq), real-time quantitative RT-PCR, and Western blotting. Results: The results showed that expression of TERT was higher in peripheral DCs of AR patients. The expression of IL10 in DCs was negatively correlated with the levels of TERT expression. Importantly, the levels of TERT mRNA in DCs were associated with the AR response in patients with AR. Endoplasmic reticulum (ER) stress promoted the expression of Tert in DCs. Sensitization with the ovalbumin-aluminum hydroxide protocol increased the expression of Tert in DCs by exacerbating ER stress. TERT interacting with c-Maf (the transcription factor of IL-10) inducing protein (CMIP) in DCs resulted in CMIP ubiquitination and degradation, and thus, suppressed the production of IL-10. Inhibition of Tert in DCs mitigated experimental AR. Conclusions: Elevated amounts of TERT were detected in DCs of patients with AR. The tolerogenic feature of DCs was impacted by TERT. Inhibited TERT attenuated experimental AR. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn's disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn's disease and identifying potential biomarkers. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall, which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH. [ABSTRACT FROM AUTHOR]

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Background: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results: We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. Conclusions: This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites. [ABSTRACT FROM AUTHOR]

In the present study, we propose the use of swabs in non-lethal sampling procedures to collect the mucosa-adhered gut microbiota from the posterior intestine of fish, and therefore, we compare the bacterial communities collected by conventional scraping and by swabbing methods. For this purpose, samples of the posterior intestine of rainbow trout (Oncorhynchus mykiss) were collected first using the swabbing approach, and after fish euthanasia, by mucosa scraping. Finally, bacterial communities were compared by 16S rRNA gene Illumina sequencing. Results from the current study revealed that similar values of bacterial richness and diversity were found for both sampling procedures. Similarly, there were no differences between procedures when using qualitative metrics (Jaccard and unweighted UniFrac) for estimating inter-individual diversity, but the quantitative metrics (Bray-Curtis and weighted UniFrac) showed a higher dispersion when samples were obtained by swabbing compared to scraping. In terms of bacterial composition, there were differences in abundance for the phyla Firmicutes and Proteobacteria. The cause of these differential abundances may be the inability of the swab to access to certain areas, such as the basal region of the intestinal villi. Moreover, swabbing allowed a higher representation of low abundant taxa, which may also have an important role in host microbiome regardless of their low abundance. Overall, our results demonstrate that the sampling method is a factor to be considered in experimental design when studying gut bacterial communities to avoid potential biases in the interpretation or comparison of results from different studies. In addition, the advantages and disadvantages of each procedure (swabbing vs scraping) are discussed in detail, concluding that swabbing can be implemented as a reliable and non-lethal procedure for posterior gut microbiota studies, which is of particular interest for animal welfare and the 3Rs principle, and may offer a wide range of novel applications. [ABSTRACT FROM AUTHOR]

Context: Cold stress is a significant factor that contributes to the imbalance of energy in piglets during their early life. Recent studies have shown that gut microbiota plays a crucial role in maintaining energy homeostasis under cold-stress conditions. Aims: This study aims to investigate the effects of cold stress on the microbiota and expression pathways in the colon and ileum of weaned piglets, providing new insights and methods for helping piglets resist cold stress. Methods: In total, 10 piglets in the cold-stress group (n = 5) and room-temperature group (n = 5) were sacrificed. Intestinal contents and mucosa samples were collected for 16S rRNA analysis. Key results: The results showed that cold stress increased the observed features and chao1 index in the colonic mucosa. The beta diversity of ileum, colon and ileum mucosa was significantly changed. Under cold stress, the relative abundance of Acholeplasma , Proteiniphilum , and Olsenella increased in the contents of the ileum and colon. The relative abundance of Ruminococcaceae sp., Butyricicoccus , and Lachnospiraceae FCS020 increased in the mucosa of the colon. Sphingomonas , Helicobacter , Cutibacterium , and Bradyrhizobium were significantly increased in the mucosa of the ileum. In predicted functions, after cold stress, the purine metabolism and degradation increased in the content and mucosa of the ileum and mucosa of the colon. The fat biosynthesis pathway increased in the content of the colon. Complex carbohydrate degradation increased in the mucosa of both. Conclusions: These findings suggest that cold stress has a significant impact on the species richness, composition, and predicted functions of the microbiota in the ileum and colon of piglets, with these effects varying depending on the location within the gut. Implications: Therefore, we can help piglets resist cold stress by modifying the structure of gut microbiota through the addition of probiotics or adjusting the composition of their diet. Cold stress of piglets is a serious problem in the breeding industry in many countries, which can lead to a large number of deaths and losses of piglets. Under cold stress, the intestinal microorganisms of piglets will undergo significant changes, and the purine metabolism and fat synthesis pathways will also be up-regulated. Therefore, it is possible to help piglets resist cold stress by adding probiotics and changing diet structure. [ABSTRACT FROM AUTHOR]

Recent advances in endoscopic technology have allowed detailed observation of the gastric mucosa, including Raman microscopy and spectroscopy. To explore the possibilities for future diagnostic use, we discuss the measurements and molecular markers found in this tissue. The Raman spectra of 16 samples of antral mucosa and 16 samples of corpus gastric mucosa obtained from healthy donors were analysed. A stable protocol for measuring reproducible spectra was established. These data suggest that many biomarkers can be used for the rapid analysis of metabolic states and future investigations into the pathogenesis of gastrointestinal diseases.

ABSTRACT Nasopharyngeal carriage of staphylococci spreads potentially pathogenic strains into (peri)oral regions and increases the chance of cross-infections. Some laboratory strains can also move rapidly on hydrated agar surfaces, but the biological relevance of these observations is not clear. Using soft-agar [0.3% (wt/vol)] plate assays, we demonstrate the rapid surface dispersal of (peri)oral isolates of Staphylococcus aureus and Staphylococcus epidermidis and closely related laboratory strains in the presence of mucin glycoproteins. Mucin-induced dispersal was a stepwise process initiated by the passive spreading of the growing colonies followed by their rapid branching (dendrites) from the colony edge. Although most spreading strains used mucin as a growth substrate, dispersal was primarily dependent on the lubricating and hydrating properties of the mucins. Using S. aureus JE2 as a genetically tractable representative, we demonstrate that mucin-induced dendritic dispersal, but not colony spreading, is facilitated by the secretion of surfactant-active phenol-soluble modulins (PSMs) in a process regulated by the agr quorum-sensing system. Furthermore, the dendritic dispersal of S. aureus JE2 colonies was further stimulated in the presence of surfactant-active supernatants recovered from the most robust (peri)oral spreaders of S. aureus and S. epidermidis. These findings suggest complementary roles for lubricating mucins and staphylococcal PSMs in the active dispersal of potentially pathogenic strains from perioral to respiratory mucosae, where gel-forming, hydrating mucins abound. They also highlight the impact that interspecies interactions have on the co-dispersal of S. aureus with other perioral bacteria, heightening the risk of polymicrobial infections and the severity of the clinical outcomes.IMPORTANCEDespite lacking classical motility machinery, nasopharyngeal staphylococci spread rapidly in (peri)oral and respiratory mucosa and cause cross-infections. We describe laboratory conditions for the reproducible study of staphylococcal dispersal on mucosa-like surfaces and the identification of two dispersal stages (colony spreading and dendritic expansion) stimulated by mucin glycoproteins. The mucin type mattered as dispersal required the surfactant activity and hydration provided by some mucin glycoproteins. While colony spreading was a passive mode of dispersal lubricated by the mucins, the more rapid and invasive form of dendritic expansion of Staphylococcus aureus and Staphylococcus epidermidis required additional lubrication by surfactant-active peptides (phenol-soluble modulins) secreted at high cell densities through quorum sensing. These results highlight a hitherto unknown role for gel-forming mucins in the dispersal of staphylococcal strains associated with cross-infections and point at perioral regions as overlooked sources of carriage and infection by staphylococci.

Malignant melanoma originates from melanoma cells, which derive from the neuroectoderm of the ectodermal mucosa. The chameleonic presentation of malignant melanoma, its often asymptomatic nature, the rarity of the lesion, the grim prognosis, and the imperative for highly specialized treatment are critical factors that merit careful consideration. Herein, we report a compilation of five cases of malignant melanomas occurring at unusual anatomical locations, which were initially misdiagnosed, which on careful analysis with the use of immuno-histochemical stains were correctly diagnosed as malignant melanoma.

Introduction: Alterations in the gut immune system have been implicated in various diseases. The challenge of obtaining gut tissues from healthy individuals, commonly performed via surgical explants, has limited the number of studies describing the phenotype and function of gut-derived immune cells in health. Methods: Here, by means of recto-sigmoid colon biopsies obtained during routine care (colon cancer screening in healthy adults), the phenotype and function of immune cells present in the gut were described and compared to those found in blood. Results: The proportion of CD4+, CD8+, MAIT, γδ+ T, and NK cells phenotype, expression of integrins, and ability to produce cytokine in response to stimulation with PMA and ionomycin. T cells in the gut were found to predominantly have a memory phenotype as compared to T cells in blood where a naïve phenotype predominates. Recto-sigmoid mononuclear cells also had higher PD-1 and Ki67 expression. Furthermore, integrin expression and cytokine production varied by cell type and location in blood vs. gut. Discussion: These findings demonstrate the differences in functionality of these cells when compared to their blood counterparts and validate previous studies on phenotype within gut-derived immune cells in humans (where cells have been obtained through surgical means). This study suggests that recto-sigmoid biopsies collected during colonoscopy can be a reliable yet more accessible sampling method for follow up of alterations of gut derived immune cells in clinical settings. [ABSTRACT FROM AUTHOR]

Malignant melanoma originates from melanoma cells, which derive from the neuroectoderm of the ectodermal mucosa. The chameleonic presentation of malignant melanoma, its often asymptomatic nature, the rarity of the lesion, the grim prognosis, and the imperative for highly specialized treatment are critical factors that merit careful consideration. Herein, we report a compilation of five cases of malignant melanomas occurring at unusual anatomical locations, which were initially misdiagnosed, which on careful analysis with the use of immuno-histochemical stains were correctly diagnosed as malignant melanoma. [ABSTRACT FROM AUTHOR]

Interleukin-22 (IL-22) is an important cytokine in the intestinal environment. IL-22 is mainly produced by immune cells and targeted at nonimmune cells such as epithelial and stromal cells in a broad array of tissues such as - but not restricted to- the liver and adipose tissue. IL-22 therefore connects immune functions with metabolic functions of the host, and since it is induced by the microbiota, connects host functioning to the outside environment. IL-22 induces epithelial cell proliferation aiding in rapid epithelium regeneration and wound healing. Additionally, IL-22 activates antiapoptotic genes and DNA damage response pathways, enhancing epithelial cell survival. Recently, it has also been shown that IL-22 induces Paneth cell differentiation in humans. However, IL-22 can also contribute to intestinal epithelium damage and reduces microbial diversity in the intestine directly or indirectly by inducing excessive antimicrobial peptide production by epithelial cells. Moreover, IL-22 enhances angiogenesis and may therefore support tumorigenesis in the intestine. In conclusion, it appears that whether IL-22 has a beneficial or harmful effect in the mammalian intestine largely depends on its regulation. This review aims to provide a comprehensive overview of the current literature and emphasizes that IL-22 signaling outcome depends on the timing and duration of IL-22 production, the presence of it regulators such as IL-22BP, and the specific location of the cytokine production in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Gastrointestinal simulations in vitro have only limited approaches to analyze the microbial communities inhabiting the mucosal compartment. Understanding and differentiating gut microbial ecosystems is crucial for a more comprehensive and accurate representation of the gut microbiome and its interactions with the host. Herein is suggested, in a short-term and static set-up (named "M-batches"), the analysis of mucosal and luminal populations of inhabitants of the human colon. After varying several parameters, such as the fermentation volume and the fecal inoculum (single or pool), only minor differences in microbial composition and metabolic production were identified. However, the pool created with feces from five donors and cultivated in a smaller volume (300 mL) seemed to provide a more stable luminal ecosystem. The study of commercially available coffee and green tea in the M-batches suggested some positive effects of these worldwide known beverages, including the increase in butyrate-producing bacteria and lactobacilli populations. We hope that this novel strategy can contribute to future advances in the study of intestinal ecosystems and host-microbe relationships and help elucidate roles of the microbiome in health and disease. [ABSTRACT FROM AUTHOR]

Oral cancer is the most prevalent head and neck cancer. Although tumor markers have been investigated for detecting the progression and prognosis of oral cancer, no reliable marker has been identified. We investigated the expression of ATP binding cassette subfamily B member 5 (ABCB5) positive stem cells in oral squamous cell carcinoma (OSCC) and in inflammatory gingival hyperplasia. We used tissue samples from normal subjects, patients with inflammatory gingival hyperplasia, and patients with OSCC. Samples were investigated using anti-ABCB5 monoclonal antibody immunohistochemistry to detect epithelial stem cells. Staining density, intensity, and immunoreactive scores of ABCB5 were analyzed for the three study groups. We found ABCB5 immunostaining in all three study groups, but different distributions of ABCB5 expression in different layers of the epithelium. We found no significant difference in staining intensity between inflammatory hyperplasia and normal mucosa, but we found significantly stronger expression in OSCC compared to normal and inflammatory hyperplasia individually. Elevated expression of ABCB5 in OSCC suggests an increased subpopulation of tumor cells with an undifferentiated stem cell phenotype, which facilitates cancer initiation and progression. [ABSTRACT FROM AUTHOR]

Methotrexate related lymphoproliferative disorder is a lymphoma that occurs in the gingiva, buccal mucosa, and tongue as a consequence of long-term methotrexate administration, and its association with osteonecrosis of the jaws has also been reported. T-cell dominant polymorphic type is rare lymphoproliferative disorder; however, its association with peri-implantitis has not been reported. Here, we report a case of long-term methotrexate administration related T-cell dominant polymorphic lymphoproliferative disorder associated with peri-implantitis. An 80-year-old female patient with a chief complaint of swelling of the right mandibular mucosa around the implant was referred to our hospital for the treatment of intractable gingival ulcer. Intraoral view revealed bone exposure and ulcer in the lingual mucosa of mandibular implant. Biopsy was performed from gingival ulcer and polymorphic methotrexate related lymphoproliferative disorder was diagnosed. The patient recovered from the ulcer and pain after methotrexate withdrawal; however, bone exposure remained. Sequestrectomy was subsequently performed under local anesthesia. The patient showed no signs of recurrence 8 months after operation. Our report will shed light on the treatment and diagnosis of T-cell dominant polymorphic MTX-LPD. Further case studies and research may be needed to develop a better understanding of the disease. [ABSTRACT FROM AUTHOR]

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Objective: This research assessed the efficiencies of aloe vera, 0.1% triamcinolone acetonide, and 5% amlexanox in the management of OLP. Materials and Methods: A total of 120 participants diagnosed with oral lichen planus (OLP) were equally divided into three groups and treated with: aloe vera, (Group A), 0.1% triamcinolone acetonide (Group B), and 5% amlexanox (Group C) topical medicaments. The patients were evaluated for pain, using the visual analogue scale (VAS). They were also evaluated for ulcerative lesion type and erosive area on days 1, 7, and 15 of the study. Results: There was a statistically considerable decrease in the VAS pain scale score, reduction in the erosive area on buccal mucosa, and healing of ulcer from day 1st to 15th day with all three tested drugs. Conclusion: All drugs used in this study; aloe vera, triamcinolone acetonide, and amlexanox were effective in treating OLP patients.

Background: Differences in the embryonic development of the colonic mucosa determine the physiological embryonic-anatomical asymmetry of its structure and can manifest themselves via different molecular phenotypes (expression profiles) of the colon segments. These molecular characteristics are hypothesized to determine differences in the carcinogenesis mechanisms and influence the prognosis of right- or left-sided colorectal cancer (CRC). Studies of the tumors molecular phenotypes depending on their localization may be of interest for assessment of the prognosis and choice of treatment for CRC. Aim: To perform comparative analysis of molecular phenotypes of the normal colonic mucosa and adenocarcinoma CRC tissues depending on the natural embryonic anatomic asymmetry of the colon. Materials and methods: We performed a retrospective study of molecular phenotypes (mRNA expression of 61 genes) from different embryonic-anatomical parts of healthy colon and CRC. The normal group included 254 samples of mucosa from three different parts of the colon from 74 healthy donors who had no cancer and no organic abnormalities of the colon, including 90 samples from the right colon, 116 from the left colon, and 48 from the rectum. The CRC group consisted of 154 samples of localized stage T1–4N0–2M0 adenocarcinoma from 154 patients who had not received neoadjuvant radio- and chemotherapy, including 40 samples from the right colon, 54 from the left colon, and 60 from the rectum. The relative mRNA abundance of 61 genes was assessed by reverse-transcriptase polymerase chain reaction. In both groups, the resulting expression phenotypes were compared between the anatomical parts of the colon. Statistical management of the data included the discriminant analysis with stepwise inclusion of variables. Results: Based on the assessment of the mRNA level of the studied genes, a discriminant model was built that allows for classification of the normal group samples according to their anatomic origin in the colon with an accuracy of 95.8%. The most significant (p 0.05) for classification are the following 19 genes: CCND1, SCUBE2, TERT, BAG1, NDRG, IL1b, IL2Ra, IL7, ESR1, TGFb, IGF1, MMP9, MMP11, PAPPA, CD45, CD69, TLR2, TLR4, LIFR. The discriminant model built for the CRC group included 27 genes and made it possible to differentiate samples from three parts of colon with an accuracy of 75.2%. A statistically significant (p 0.05) contribution to the samples differentiation by the discriminant model was made by the COX-2, BIRC5, LIFR, TPA, IL1b, MMP11, MMP7, and P16INK4A genes. When combining samples from the two groups into one model in accordance with their embryonic-anatomical origin, there was a clear separation of tumor tissue samples and healthy colonic mucosa in the discriminant function space. Conclusion: The analysis of CRC gene expression profiles using the discriminant model showed that genetic changes in the colonic mucosa in CRC flatten the molecular phenotypic boundaries of the embryonic-anatomical parts. These changes are specific to CRC, forming a particular “pathological” molecular phenotype.

Abstract Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry. Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut. To secure better postnatal gut colonization, we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period. Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli (ETEC). Methods Seventy-two 1-day-old piglets were randomized to four groups: colonic microbiota transplantation (CMT, n = 18), colonic content filtrate transplantation (CcFT, n = 18), gastric microbiota transplantation (GMT, n = 18), or saline (CON, n = 18). Inoculations were given on d 2 and 3 of life, and all piglets were milk-fed until weaning (d 20) and shortly after challenged with ETEC (d 24). We assessed growth, diarrhea prevalence, ETEC concentration, organ weight, blood parameters, small intestinal morphology and histology, gut mucosal function, and microbiota composition and diversity. Results Episodes of diarrhea were seen in all groups during both the milk- and the solid-feeding phase, possibly due to stress associated with single housing. However, CcFT showed lower diarrhea prevalence on d 27, 28, and 29 compared to CON (all P

Background: Oral lichen planus (OLP) is a chronic inflammatory condition that primarily affects the oral mucosa. While the exact cause of OLP remains unclear, recently, there has been particular interest in researching the potential link between OLP and thyroid gland disorders. Methods and Results: A total of 100 subjects participated in our research. Among them, 50 were patients (80% women and 20% men) diagnosed with OLP (the main group [MG]), and 50 subjects (60% women and 40% men) with various other oral mucosa concerns (aphthous stomatitis, burning mouth syndrome, herpetic stomatitis, and geographic tongue) comprised the comparison group [CG]. All participants underwent a comprehensive assessment of thyroid function, which included the measurement of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and an ultrasound examination of the thyroid gland performed by an endocrinologist. Our results reveal a noteworthy gender-based difference in the occurrence of mucosal disorders, indicating a predominance of females. MG had a significantly higher prevalence of hypothyroidism, with 46% of patients affected. In contrast, in CG, the prevalence of hypothyroidism was lower, at 16%, and this difference was statistically significant (P=0.0012). In MG, 50% of cases were found to be in a euthyroid state. In contrast, in CG, a larger proportion (80%) of patients were in a euthyroid state, and this difference was statistically significant (P=0.0017). Conclusion: Our study has identified a significant and positive association between hypothyroidism and OLP. We recommend that individuals diagnosed with OLP, especially women, consider undergoing routine screening for thyroid disease as part of their healthcare regimen.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group’s objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. An evaluation revealed surrogate characteristics that were satisfactory and exhibited good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

Background: Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry. Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut. To secure better postnatal gut colonization, we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period. Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli (ETEC). Methods: Seventy-two 1-day-old piglets were randomized to four groups: colonic microbiota transplantation (CMT, n = 18), colonic content filtrate transplantation (CcFT, n = 18), gastric microbiota transplantation (GMT, n = 18), or saline (CON, n = 18). Inoculations were given on d 2 and 3 of life, and all piglets were milk-fed until weaning (d 20) and shortly after challenged with ETEC (d 24). We assessed growth, diarrhea prevalence, ETEC concentration, organ weight, blood parameters, small intestinal morphology and histology, gut mucosal function, and microbiota composition and diversity. Results: Episodes of diarrhea were seen in all groups during both the milk- and the solid-feeding phase, possibly due to stress associated with single housing. However, CcFT showed lower diarrhea prevalence on d 27, 28, and 29 compared to CON (all P < 0.05). CcFT also showed a lower ETEC prevalence on d 27 (P < 0.05). CMT showed a higher alpha diversity and a difference in beta diversity compared to CON (P < 0.05). Growth and other paraclinical endpoints were similar across groups. Conclusion: In conclusion, only CcFT reduced ETEC-related post-weaning diarrhea. However, the protective effect was marginal, suggesting that higher doses, more effective modalities of administration, longer treatment periods, and better donor quality should be explored by future research to optimize the protective effects of transplantation. [ABSTRACT FROM AUTHOR]

The permeability of the oral or nasal mucosa is higher than that of the skin. Mucosa permeability depends mainly on the thickness and keratinization degree of the tissues. Their permeability barrier is conditioned by the presence of certain lipids. This work has the main aim of reinforcing the barrier effect of oral mucosa with a series of formulations to reduce permeation. Transmembrane water loss of different formulations was evaluated, and three of them were selected to be tested on the sublingual mucosa permeation of drugs. Caffeine, ibuprofen, dexamethasone, and ivermectin were applied on porcine skin, mucosa, and modified mucosa in order to compare the effectiveness of the formulations. A similar permeation profile was obtained in the different membranes: caffeine > ibuprofen~dexamethasone > ivermectin. The most efficient formulation was a liposomal formulation composed of lipids that are present in the skin stratum corneum. Impermeability provided by this formulation was notable mainly for the low-molecular-weight compounds, decreasing their permeability coefficient by between 40 and 80%. The reinforcement of the barrier function of mucosa provides a reduction or prevention of the permeation of different actives, which could be extrapolated to toxic compounds such as viruses, contaminants, toxins, etc. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effects of Zn sources, used with potato fiber (PF) or lignocellulose (LC), on electrolyte concentration and the mucus layer in the large intestine of pigs. The experiment involved 24 barrows with an initial body weight of 10.8 ± 0.82 kg, divided into four groups fed the following diets: LC and ZnSO4, LC and Zn glycinate (ZnGly), PF and ZnSO4, or PF and ZnGly. Fiber supplements provided 10 g crude fiber/kg diet, while Zn additives introduced 120 mg Zn/kg diet. After four weeks of feeding, the pigs were sacrificed and digesta and tissue samples were taken from the cecum and colon. PF increased the water content and decreased the phosphorus concentration in the large intestine in comparison with LC. PF also increased calcium, iron, and chloride concentrations in the descending colon. Mucus layer thickness and histological parameters of the large intestine were not affected. ZnGly diets increased MUC12 expression in the cecum as compared to the LC-ZnSO4 group. In the ascending colon, the PF-ZnGly diet increased MUC5AC expression, while both PF groups had greater MUC20 expression in comparison with the LC-ZnSO4 group. In the transverse colon, the LC-ZnGly group and both PF groups had higher MUC5AC expression in comparison with the LC-ZnSO4 group, and both ZnGly groups had higher MUC20 expression than ZnSO4 groups. PF and ZnGly increased MUC4 and MUC5AC expression in the descending colon. PF and ZnGly may exert a beneficial effect on colon health in pigs by upregulating the expression of the MUC5AC and MUC20 genes and are more effective than LC and ZnSO4. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is classified as a civilization disease and is being diagnosed in an increasing number of patients. Hypertension and diabetes mellitus often coexist in hemodialyzed patients. The aim of the present study was to identify publications on the oral cavity status of multimorbid hemodialyzed adult patients additionally diagnosed with hypertension and/or diabetes mellitus, published between 2012 and 2022 to establish evidence of the impact of hypertension and diabetes mellitus on the oral status of hemodialyzed patients. Scopus and Web of Science databases were searched. Eight articles were included in the review. In total, 3 articles discussed oral hygiene in hemodialyzed patients, 4 discussed periodontal status, 3 discussed mucosa condition and saliva parameters, and 3 discussed the problem of Candidiasis infections. The conclusions were as follows: there is still a limited number of publications discussing the oral status of hemodialyzed patients diagnosed with hypertension; involved articles have proven that coexisting diseases can influence the oral cavity status of hemodialyzed patients and cause periodontal disorders, lower hygiene status, saliva parameters and make the risk of Candida infections higher. [ABSTRACT FROM AUTHOR]

Simple Summary: Many animals exhibit immune cell aggregation in the conjunctiva which prevents the invasion of viruses and bacteria. However, the features and functions of conjunctival immune cell aggregates in cows are not fully understood. Microscopic observations confirmed conjunctival immune cell aggregation in calves and adult cows, similar to that in other animals. However, these structures of calves are small and poor in immune cells compared to those of adult cows. These results suggest that cows have a conjunctival local immune system similar to that of other animals, and that conjunctival immune function is weak in calves. These findings may help to prevent infectious diseases in cows. The conjunctiva-associated lymphoid tissue (CALT) has been used as a target site for mucosal vaccinations in several animals. In this study, we compared the morphological features of CALT in the eyelid and third eyelid between Holstein calves and adult cows. In the eyelids, CALTs in the form of diffused lymphoid tissue (DLT) and lymphatic follicles (LF) were observed, where DLTs were dominant and LFs were scarce. The CALTs of cows comprised T-, B-cells, macrophages, and antigen-presenting cells (APCs). In particular, B-cells were dominant except in the eyelids of the calves. The epithelial layer covering the CALT is often discontinuous and lacks goblet cells. Cytokeratin18 is strongly expressed in the epithelial layer covering the CALT, except in the third eyelids of adult cows. IgA-positive cells were diffusely distributed in the lamina propria of the conjunctiva of the eyelids and third eyelids. The eyelid CALT area in calves was lower than that in adult cows. Furthermore, the CALT of calves had a lower cellularity of B-cells and a higher cellularity of macrophages than that of adult cows. These histological characteristics indicate that CALT plays a role in the mucosal immune-inductive and effector sites. Furthermore, lower cellularity of B-cells in the CALT of calves indicates that the function of CALT as a mucosal immune induction site is less developed in calves than in adult cows. [ABSTRACT FROM AUTHOR]

Background: The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria—a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS. Methods: Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5 mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content. Results: Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups. Conclusion: Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes. [ABSTRACT FROM AUTHOR]

Under normal circumstances, gastric mucosa only exists within the stomach. However, in certain situations, gastric mucosal tissue may undergo ectopia, commonly occurring in the esophagus and intestine, with rare occurrences within the stomach itself. A comprehensive literature review was performed to understand the distinct characteristics of ectopic gastric mucosa (EGM) in the stomach and investigate a rare incident of this disease, providing an in-depth analysis of the clinical, histopathologic, and differential diagnostic findings. The case was a 47-year-old man with acid reflux, heartburn, abdominal distension, and diarrhea (5-10 times daily) for >10 years. A gastroscope indicated a submucosal protuberance lesion in the gastric body that felt hard with biopsy forceps. A well-defined nodule under the mucosal muscle was revealed microscopically, composed of epithelial elements and no atypia. Immunohistochemical staining demonstrated similar EGM expression patterns compared with normal gastric mucosa. The present case report highlights the importance of accurate EGM diagnosis and understanding. [ABSTRACT FROM AUTHOR]

Background: Until recently, most data regarding the effects of non‐barrier contraceptives on the mucosal microbiome have derived from observational studies, which are potentially biased due to behavioral confounders that may mask their true biological effects. Method of Study: This narrative review summarises recent evidence of the effect of contraceptives on the cervicovaginal microbiome, emphasising data obtained through randomized trials. Results: Good quality data describe that initiation of long‐acting progestin‐only contraceptives, including levonorgestrel (LNG)‐implant and the injectables depot‐medroxyprogesterone acetate (DMPA‐IM) and norethisterone enanthate (NET‐EN) do not alter the mucosal microbial environment. Likewise, no strong evidence exists that the use of oral contraceptive pills (OCPs) is associated with alterations of the vaginal microbiome or increased risk of bacterial sexually transmitted infections (STIs). Limited data on the effect of intravaginal rings (IVRs) on the mucosal environment exist and show conflicting effects on the vaginal microbiota. Copper intrauterine device (Cu‐IUD) initiation has been associated with bacterial vaginosis (BV) acquisition, including in a randomized trial. LNG‐IUDs may have similar affects but need to be evaluated further. Conclusion: Different synthetic hormones have divergent effects on the microbiome and therefore novel hormonal methods need to be rigorously evaluated. Furthermore, the addition of antiretrovirals into multipurpose technologies may alter the effects of the hormonal component. There is thus a critical need to improve our understanding of the biological effects of contraceptive hormones and delivery methods with different pharmacokinetic and chemical properties on the mucosal microbiome in rigorous trials, to inform the development of novel contraceptives and improve individual family planning guidance. [ABSTRACT FROM AUTHOR]

Abstract Traditionally, molecular mechanisms of pathogenesis for infectious agents were studied in cell culture or animal models but have limitations on the extent to which the resulting data reflect natural infection in humans. The COVID-19 pandemic has highlighted the urgent need to rapidly develop laboratory models that enable the study of host-pathogen interactions, particularly the relative efficacy of preventive measures. Recently, human and animal ex vivo tissue challenge models have emerged as a promising avenue to study immune responses, screen potential therapies and triage vaccine candidates. This approach offers the opportunity to closely approximate human disease from the perspective of pathology and immune response. It has advantages compared to animal models which are expensive, lengthy and often require containment facilities. Herein, we summarize some recent advances in the development of ex vivo tissue challenge models for COVID-19, HIV-1 and other pathogens. We focus on the contribution of these models to enhancing knowledge of host-pathogen interactions, immune modulation, and their value in testing therapeutic agents. We further highlight the advantages and limitations of using ex vivo challenge models and briefly summarize how the use of organoids provides a useful advancement over current approaches. Collectively, these developments have enormous potential for the study of infectious diseases. [ABSTRACT FROM AUTHOR]

The development of tuberculosis (TB) vaccines has been hindered by the complex nature of Mycobacterium tuberculosis (M.tb) and the absence of clearly defined immune markers of protection. While Bacillus Calmette-Guerin (BCG) is currently the only licensed TB vaccine, its effectiveness diminishes in adulthood. In our previous research, we identified that boosting BCG with an intranasally administered chimpanzee adenovirus expressing the PPE15 antigen of M.tb (ChAdOx1.PPE15) improved its protection. To enhance the vaccine’s efficacy, we combined PPE15 with the other three members of the Esx-5a secretion system and Ag85A into a multi-antigen construct (5Ag). Leveraging the mucosal administration safety of ChAdOx1, we targeted the site of M.tb infection to induce localized mucosal responses, while employing modified vaccinia virus (MVA) to boost systemic immune responses. The combination of these antigens resulted in enhanced BCG protection in both the lungs and spleens of vaccinated mice. These findings provide support for advancing ChAdOx1.5Ag and MVA.5Ag to the next stages of vaccine development. [ABSTRACT FROM AUTHOR]

The aim of the current study was to determine whether daily fucoidan supplementation (Undaria pinnatifida extract containing >85% fucoidan, 1 g/day) for three-weeks in a double blind-placebo controlled cross-over trial (ACTRN12621000872831) could modulate alterations in faecal (calprotectin, lysozyme and IgA) and salivary (lactoferrin, lysozyme and IgA) markers of mucosal immune competence typically observed in response to both acute physical activity, and a period of intensified exercise training, in healthy recreationally active men (n = 12). Participants responded positively to the intensified training with 16–19% improvement in mean power that was not different between supplement groups. Faecal biomarkers and concentrations of lactoferrin, lysozyme and IgA from resting saliva samples were largely stable over the supplementation period. Concentrations of salivary biomarkers varied significantly over time in response to acute exercise, however differences between supplementation groups were modest. For salivary lysozyme, there was a trend for a lower magnitude of increase post-exercise (p = 0.08) and limited return towards pre-exercise in response to fucoidan. For salivary IgA, a greater acute exercise response was noted for IgA in response to fucoidan (~2.7-fold higher; p = 0.02). Different dosage and supplementation protocols and inclusion of additional immune markers should be considered in subsequent assessments of any potential benefits of fucoidan supplementation in healthy active adults. [ABSTRACT FROM AUTHOR]

[Display omitted] Mucosal surfaces serve as the primary entry points for pathogens such as SARS- CoV-2 coronavirus or HIV in the human body. Mucosal vaccination plays a crucial role to successfully induce long-lasting systemic and local immune responses to confer sterilizing immunity. However, antigen formulations and delivery methods must be properly selected since they are decisive for the quality and the magnitude of the elicited immune responses in mucosa. We investigated the significance of using particulate antigen forms for mucosal vaccination by comparing VLP- or protein- based vaccines in a mouse model. Based on a mucosal prime-boost immunization protocol combining (i) HIV- pseudotyped recombinant VLPs (HIV-VLPs) and (ii) plasmid DNA encoding HIV- VLPs (pVLPs), we demonstrated that combination of intranasal primes and intravaginal boosts is optimal to elicit both humoral and cellular memory responses in mucosa. Interestingly, our results show that in contrast to proteins, particulate antigens induce high-quality humoral responses characterized by a high breadth, long-term neutralizing activity and cross-clade reactivity, accompanying with high T follicular helper cell (T FH) response. These results underscore the potential of a VLP-based vaccine in effectively instigating long-lasting, HIV-specific immunity and point out the specific role of particulate antigen form in driving high-quality mucosal immune responses. [ABSTRACT FROM AUTHOR]