The gut microbiota influences the reactivity of the immune system, and Parabacteroides distasonis has emerged as an anti-inflammatory commensal. Here, we investigated whether its lysate could prevent severe forms of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in mice and how this preventive strategy affects the gut microbiota and immune response. Lysate of anaerobically cultured P. distasonis (Pd lysate) was orally administered to C57BL/6 mice in four weekly doses. One week later, EAE was induced and disease severity was assessed three weeks after induction. Fecal microbiota changes in both vehicle- and Pd lysate-treated animals was analyzed by 16S V3-V4 amplicon sequencing and qPCR, antimicrobial peptide expression in the intestinal mucosa was measured by qPCR, and immune cell composition in the mesenteric and inguinal lymph nodes was measured by multicolor flow cytometry. Pd lysate significantly delayed the development of EAE and reduced its severity when administered prior to disease induction. EAE induction was the main factor in altering the gut microbiota, decreasing the abundance of lactobacilli and segmented filamentous bacteria. Pd lysate significantly increased the intestinal abundance of the genera Anaerostipes, Parabacteroides and Prevotella, and altered the expression of antimicrobial peptides in the intestinal mucosa. It significantly increased the frequency of regulatory T cells, induced an anti-inflammatory milieu in mesenteric lymph nodes, and reduced the activation of T cells at the priming site. Pd lysate prevents severe forms of EAE by triggering a T regulatory response and modulating T cell priming to autoantigens. Pd lysate could thus be a future modulator of neuroinflammation that increases the resistance to multiple sclerosis.
- MeSH
- Bacteroidetes imunologie MeSH
- encefalomyelitida autoimunitní experimentální * imunologie prevence a kontrola MeSH
- myši inbrední C57BL * MeSH
- myši MeSH
- střevní mikroflóra * imunologie MeSH
- střevní sliznice imunologie mikrobiologie metabolismus MeSH
- T-lymfocyty imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Two benign adenomatous lesions are commonly recognized within the sinonasal tract, namely respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH). We present 10 hitherto unrecognized benign polypoid nasal and sinonasal tumoriform lesions having in average 3.6 cm in largest dimension, which are histogenetically related to SH and REAH. In addition to typical structures of REAH and SH, these lesions contained an additional characteristic and slightly atypical adenomatous component, which we termed atypical sinonasal glands arising in SH (ASGSH). ASGSH often produced deep red colored secretion with peripheral clearing similar to that seen in thyroid follicles. In contrast to SH, ASGSH was endowed by both secretory and myoepithelial layers and had mostly angulated shapes with snout-like protrusions into the lumens. Both layers were formed by an irregular, disorganized, and often incomplete cell lining, which had slightly atypical cytological features without mitoses. In 3 cases, ASGSHs revealed sebaceous differentiation, and in 3 cases the stroma produced a well-differentiated cartilage. Neoplastic nature of ASGSH was supported by finding of various mutations as revealed by next generation sequencing in five cases. In two cases each, we found identical mutations in BRAF gene (Val600Glu), and RET gene (Arg912Trp), respectively and in one case FAT1 gene alteration (Pro1665Leu).
- MeSH
- adenom patologie genetika MeSH
- dospělí MeSH
- hamartom * patologie genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádory nosu patologie genetika MeSH
- nádory vedlejších dutin nosních patologie genetika MeSH
- respirační sliznice patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Olfactory sensitivity to odorant molecules is a complex biological function influenced by both endogenous factors, such as genetic background and physiological state, and exogenous factors, such as environmental conditions. In animals, this vital ability is mediated by olfactory sensory neurons (OSNs), which are distributed across several specialized olfactory subsystems depending on the species. Using the phosphorylation of the ribosomal protein S6 (rpS6) in OSNs following sensory stimulation, we developed an ex vivo assay allowing the simultaneous conditioning and odorant stimulation of different mouse olfactory subsystems, including the main olfactory epithelium, the vomeronasal organ, and the Grueneberg ganglion. This approach enabled us to observe odorant-induced neuronal activity within the different olfactory subsystems and to demonstrate the impact of environmental conditioning, such as temperature variations, on olfactory sensitivity, specifically in the Grueneberg ganglion. We further applied our rpS6-based assay to the human olfactory system and demonstrated its feasibility. Our findings show that analyzing rpS6 signal intensity is a robust and highly reproducible indicator of neuronal activity across various olfactory systems, while avoiding stress and some experimental limitations associated with in vivo exposure. The potential extension of this assay to other conditioning paradigms and olfactory systems, as well as its application to other animal species, including human olfactory diagnostics, is also discussed.
- MeSH
- čich fyziologie MeSH
- čichová sliznice metabolismus MeSH
- čichové buňky * metabolismus fyziologie MeSH
- fosforylace MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- odoranty analýza MeSH
- ribozomální protein S6 * metabolismus MeSH
- vomeronazální orgán metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear. METHODS: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study. RESULTS: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants. DISCUSSION: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses. HIGHLIGHTS: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study.
- MeSH
- Alzheimerova nemoc * genetika metabolismus MeSH
- čichová sliznice metabolismus MeSH
- epigenomika MeSH
- faktor 2 související s NF-E2 genetika metabolismus MeSH
- látky znečišťující vzduch škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * MeSH
- mikro RNA metabolismus genetika MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transkriptom MeSH
- výfukové emise vozidel * toxicita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the nasal cavity, penetrates the nasal epithelial cells through the interaction of its spike protein with the host cell receptor angiotensin-converting enzyme 2 (ACE2) and then triggers a cytokine storm. We aimed to assess the biocompatibility of fullerenol nanoparticles C60(OH)40 and ectoine, and to document their effect on the protection of primary human nasal epithelial cells (HNEpCs) against the effects of interaction with the fragment of virus - spike protein. This preliminary research is the first step towards the construction of a intranasal medical device with a protective, mechanical function against SARS-CoV-2 similar to that of personal protective equipment (eg masks). METHODS: We used HNEpCs and the full-length spike protein from SARS-CoV-2 to mimic the first stage of virus infection. We assessed cell viability with the XTT assay and a spectrophotometer. May-Grünwald Giemsa and periodic acid-Schiff staining served to evaluate HNEpC morphology. We assessed reactive oxygen species (ROS) production by using 2',7'-dichlorofluorescin diacetate and commercial kit. Finally, we employed reverse transcription polymerase chain reaction, Western blotting and confocal microscopy to determine the expression of angiotensin-converting enzyme 2 (ACE2) and inflammatory cytokines. RESULTS: There was normal morphology and unchanged viability of HNEpCs after incubation with 10 mg/L C60(OH)40, 0.2% ectoine or their composite for 24 h. The spike protein exerted cytotoxicity via ROS production. Preincubation with the composite protected HNEpCs against the interaction between the spike protein and the host membrane and prevented the production of key cytokines characteristic of severe coronavirus disease 2019, including interleukin 6 and 8, monocyte chemotactic protein 1 and 2, tissue inhibitor of metalloproteinases 2 and macrophage colony-stimulating factor. CONCLUSION: In the future, the combination of fullerenol and ectoine may be used to prevent viral infections as an intranasal medical device for people with reduced immunity and damaged mucous membrane.
- MeSH
- aminokyseliny diaminové MeSH
- angiotensin konvertující enzym 2 metabolismus MeSH
- COVID-19 * prevence a kontrola MeSH
- cytokiny metabolismus MeSH
- epitelové buňky * účinky léků virologie MeSH
- fullereny * farmakologie chemie MeSH
- glykoprotein S, koronavirus * metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- nanočástice * chemie MeSH
- nosní sliznice účinky léků cytologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- SARS-CoV-2 * účinky léků MeSH
- syndrom uvolnění cytokinů * prevence a kontrola MeSH
- viabilita buněk * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
UNLABELLED: We would like to provide an updated comprehensive perspective and identify the components linked to chronic spontaneous urticaria (CSU) without specific triggers in autoimmune atrophic gastritis (AAG). AAG is an organ-specific autoimmune disease that affects the corpus-fundus gastric mucosa. Although we lack a unified explanation of the underlying pathways, when considering all paediatric patients reported in the literature, alterations result in gastric neuroendocrine enterochromaffin-like (ECL) cell proliferation and paracrine release of histamine. Several mechanisms have been proposed for the pathogenesis of CSU, with much evidence pointing towards AAG and ECL cell responses, which may be implicated as potential factors contributing to CSU. The excessive production/release of histamine into the bloodstream could cause or trigger exacerbations of CSU in AAG, independent of Helicobacter pylori; thus, the release of histamine from ECL cells may be the primary modulator. CONCLUSION: Considering the understanding of these interactions, recognising the respective roles of AAG in the pathogenesis of CSU may strongly impact the diagnostic workup and management of unexplained/refractory CSU and may inform future research and interventions in the paediatric population. WHAT IS KNOWN: • Autoimmune atrophic gastritis is a chronic immune-mediated inflammatory disease characterised by the destruction of the oxyntic mucosa in the gastric body and fundus, mucosal atrophy, and metaplastic changes. • Autoimmune atrophic gastritis in paediatric patients is important because of the poor outcome and risk of malignancy and possibly underestimated entities primarily reported in single-case reports. WHAT IS NEW: • Upper gastrointestinal inflammatory disorders, independent of H. pylori, have been implicated as potential inducing factors in the development of chronic spontaneous urticaria. • If a paediatric patient presents with symptoms such as anaemia, reduced vitamin B12 levels, recurrent urticaria with no other detectable aetiology, positive anti-parietal cell antibodies, and elevated gastrin levels, autoimmune atrophic gastritis should be considered a possible cause of chronic urticaria.
- MeSH
- autoimunitní nemoci * komplikace diagnóza MeSH
- chronická nemoc MeSH
- chronická urtikarie * etiologie patologie MeSH
- dítě MeSH
- gastritida atrofická * komplikace patologie MeSH
- gastritida * komplikace diagnóza MeSH
- Helicobacter pylori * MeSH
- histamin MeSH
- infekce vyvolané Helicobacter pylori * komplikace MeSH
- lidé MeSH
- žaludeční sliznice patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The intestinal epithelium, a rapidly renewing tissue, is characterized by a continuous cell turnover that occurs through a well-coordinated process of cell proliferation and differentiation. This dynamic is crucial for the long-term function of the gastrointestinal tract. Disruption of this process can lead to colorectal carcinoma, a common malignancy worldwide. The first part of the review focuses on the cellular composition of the epithelium and the molecular mechanisms that control its functions, and describes the pathways that lead to epithelial transformation and tumor progression. This forms the basis for understanding the development and progression of advanced colorectal cancer. The second part deals with current therapeutic approaches and presents the latest treatment options, ongoing clinical trials and new drugs. In addition, the biological and medical perspectives of the adverse effects of therapies and models of regeneration of the intestinal epithelium are highlighted and, finally, future treatment options are discussed.
- MeSH
- kolorektální nádory * terapie patologie MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- onkologové MeSH
- střevní sliznice patologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Súčasťou poskytovania ošetrovateľskej starostlivosti v rámci zabezpečenia hygieny u pacienta počas hospitalizácie je starostlivosť o ústnu dutinu geriatrického pacienta. Cieľom príspevku je poukázať práve na špecifiká starostlivosti o ústnu dutinu, kedy je nevyhnutné posúdenie stavu pier, chrupu, slizníc, zubov a ďasien. Zhodnotenie sebestačnosti, schopnosti a zručnosti seniora pri vykonávaní hygieny ústnej dutiny má tiež svoje významné miesto v starostlivosti o ústa seniora. Poznaním príčin vzniku prejavov komplikácií v ústnej dutine dokáže ošetrujúci poskytnúť kvalitnú ošetrovateľskú starostlivosť, predchádzať orálnym ochoreniam a zvládať možný výskyt komplikácií vyplývajúcich z celkových ochorení.
Part of the provision of nursing care as part of ensuring hygiene for the patient during hospitalization is the care of the oral cavity of the geriatric patient. The aim of the paper is to point out the specifics of oral care, when it is necessary to assess the condition of the lips, teeth, mucous membranes, teeth and gums. The evaluation of the senior’s self-sufficiency, ability and skills in performing oral hygiene also has an important place in the care of the senior’s mouth. By knowing the causes of complications in the oral cavity, the caregiver can provide quality nursing care, prevent oral diseases and manage the possible occurrence of complications resulting from general diseases.
- MeSH
- bulózní pemfigoid etiologie komplikace ošetřování prevence a kontrola terapie MeSH
- cheilitida etiologie komplikace ošetřování prevence a kontrola terapie MeSH
- geriatrické ošetřovatelství MeSH
- kandidóza etiologie komplikace ošetřování prevence a kontrola terapie MeSH
- leukoplakie etiologie komplikace ošetřování prevence a kontrola terapie MeSH
- nemoci jazyka etiologie komplikace ošetřování prevence a kontrola terapie MeSH
- nemoci úst etiologie komplikace ošetřování prevence a kontrola terapie MeSH
- orální hygiena MeSH
- orální zdraví MeSH
- senioři MeSH
- stomatitida etiologie komplikace ošetřování terapie MeSH
- ústní sliznice patologie MeSH
- Check Tag
- senioři MeSH
- MeSH
- chronická pankreatitida metabolismus patofyziologie MeSH
- chuťová percepce MeSH
- Crohnova nemoc metabolismus patofyziologie MeSH
- cystická fibróza metabolismus patofyziologie MeSH
- enterocyty fyziologie MeSH
- gastrointestinální absorpce fyziologie MeSH
- gastrointestinální nemoci * metabolismus patofyziologie MeSH
- kyselina linolová metabolismus MeSH
- lidé MeSH
- mastné kyseliny * fyziologie metabolismus MeSH
- potravinová intolerance MeSH
- střeva metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Malabsorpční syndromy představují rozsáhlou skupinu onemocnění, pro která je typická porucha intraluminálního trávení či vstřebávání živin. Klinicky se manifestují jako průjem, steatorea, nadýmání anebo neprospívání. Některé jednotky mohou být doprovázeny i specifickými příznaky, jako jsou např. otoky, paličkovité prsty a perianální exantém. Článek má za cíl na základě recentních poznatků malabsorpční syndromy přehledně klasifikovat a shrnout jejich etiologii, etiopatogenezi a klinickou manifestaci. Nedílnou součástí textu je rovněž přiblížení aktuálních diagnostických a léčebných postupů. V souladu se zaměřením rubriky budou diskutovány zejména nozologické jednotky s častějším výskytem. Vzácnější choroby (např. malabsorpce při reakci štěpu proti hostiteli) budou zmíněny jen okrajově a čtenáři budou poskytnuty recentní zdroje s podrobnějšími informacemi.
Malabsorption syndromes represent a large group of diseases characterized by impaired intraluminal digestion or nutrient absorption and typically manifest as diarrhea, steatorrhea, bloating and/or failure to thrive. Some diseases may be accompanied by specific symptoms such as oedema, digital clubbing and perianal exanthema. This article aims to classify malabsorption syndromes based on recent findings and summarize their etiology, etiopathogenesis and clinical manifestation. We review current diagnostic and therapeutic approaches. In accordance with the section in which the text will be published, frequent nosological entities will be discussed. Rarer diseases (such as malabsorption due to graft versus host disease) will be mentioned briefly, we direct readers to relevant and detailed sources.
- MeSH
- celiakie diagnóza etiologie komplikace MeSH
- cholestáza diagnóza etiologie MeSH
- diferenciální diagnóza MeSH
- exsudativní enteropatie diagnóza etiologie komplikace MeSH
- lidé MeSH
- malabsorpční syndromy * diagnóza etiologie farmakoterapie klasifikace patofyziologie MeSH
- nemoci žaludku diagnóza klasifikace komplikace patofyziologie MeSH
- střevní sliznice patologie MeSH
- žaludeční sliznice patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
