- MeSH
- anastomóza chirurgická metody škodlivé účinky MeSH
- duodenum * chirurgie MeSH
- jejunum * chirurgie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- MeSH
- endosonografie * metody MeSH
- intervenční ultrasonografie * MeSH
- lidé MeSH
- stenty * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- kazuistiky MeSH
Exosomes are small vesicles of endosomal origin that are released by almost all cell types, even those that are pathologically altered. Exosomes widely participate in cell-to-cell communication via transferring cargo, including nucleic acids, proteins, and other metabolites, into recipient cells. Tumour-derived exosomes (TDEs) participate in many important molecular pathways and affect various hallmarks of cancer, including fibroblasts activation, modification of the tumour microenvironment (TME), modulation of immune responses, angiogenesis promotion, setting the pre-metastatic niche, enhancing metastatic potential, and affecting therapy sensitivity and resistance. The unique exosome biogenesis, composition, nontoxicity, and ability to target specific tumour cells bring up their use as promising drug carriers and cancer biomarkers. In this review, we focus on the role of exosomes, with an emphasis on their protein cargo, in the key mechanisms promoting cancer progression. We also briefly summarise the mechanism of exosome biogenesis, its structure, protein composition, and potential as a signalling hub in both normal and pathological conditions. Video Abstract.
BACKGROUND: E. coli O83 (Colinfant Newborn) is a Gram-negative (G-) probiotic bacterium used in the clinic. When administered orally, it reduces allergic sensitisation but not allergic asthma. Intranasal administration offers a non-invasive and convenient delivery method. This route bypasses the gastrointestinal tract and provides direct access to the airways, which are the target of asthma prevention. G- bacteria such as E. coli O83 release outer membrane vesicles (OMVs) to communicate with the environment. Here we investigate whether intranasally administered E. coli O83 OMVs (EcO83-OMVs) can reduce allergic airway inflammation in mice. METHODS: EcO83-OMVs were isolated by ultracentrifugation and characterised their number, morphology (shape and size), composition (proteins and lipopolysaccharide; LPS), recognition by innate receptors (using transfected HEK293 cells) and immunomodulatory potential (in naïve splenocytes and bone marrow-derived dendritic cells; BMDCs). Their allergy-preventive effect was investigated in a mouse model of ovalbumin-induced allergic airway inflammation. RESULTS: EcO83-OMVs are spherical nanoparticles with a size of about 110 nm. They contain LPS and protein cargo. We identified a total of 1120 proteins, 136 of which were enriched in OMVs compared to parent bacteria. Proteins from the flagellum dominated. OMVs activated the pattern recognition receptors TLR2/4/5 as well as NOD1 and NOD2. EcO83-OMVs induced the production of pro- and anti-inflammatory cytokines in splenocytes and BMDCs. Intranasal administration of EcO83-OMVs inhibited airway hyperresponsiveness, and decreased airway eosinophilia, Th2 cytokine production and mucus secretion. CONCLUSIONS: We demonstrate for the first time that intranasally administered OMVs from probiotic G- bacteria have an anti-allergic effect. Our study highlights the advantages of OMVs as a safe platform for the prophylactic treatment of allergy. Video Abstract.
- MeSH
- alergie * prevence a kontrola metabolismus MeSH
- bronchiální astma * metabolismus MeSH
- Escherichia coli MeSH
- extracelulární vezikuly * metabolismus MeSH
- HEK293 buňky MeSH
- lidé MeSH
- lipopolysacharidy MeSH
- myši MeSH
- přirozená imunita MeSH
- probiotika * farmakologie MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
INTRODUCTION: Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting. METHODS: The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed. RESULTS: Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure. CONCLUSION: Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03992417. Video Abstract.
- MeSH
- atopická dermatitida * farmakoterapie epidemiologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- ekzém * MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- kvalita života MeSH
- lidé MeSH
- mladiství MeSH
- prospektivní studie MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Percutaneous endoscopic cecostomy (PEC) is a viable treatment option for patients with persistent or recurrent acute colonic pseudo-obstruction (ACPO; Ogilvie's syndrome). It should be generally considered in patients that are refractory to pharmacologic and endoscopic decompression, especially those not amenable to surgical intervention due to an increased perioperative risk. Physicians are rather unfamiliar with this approach given the limited number of reports in the literature and paucity of guideline resources, although guidelines concerning ACPO and covering the role of endoscopy were recently published by three major expert societies, all within the last 2 years. PATIENTS AND METHODS: We retrospectively identified three consecutive patients who underwent PEC placement at a Czech tertiary referral center between May 2018 and December 2021: all for recurrent ACPO. In addition, we summarized the current guidelines in order to present the latest knowledge related both to the procedure and management approach in patients with ACPO. RESULTS: The placement of PEC was successful and resulted in clinical improvement in all cases without any adverse events. CONCLUSION: The results of our experience are in line with previous reports and suggest that PEC may become a very useful tool in the armamentarium of modalities utilized to treat ACPO. Furthermore, the availability of guideline resources now offers comprehensive guidance for informed decision-making and the procedural aspects.
- MeSH
- bederní obratle chirurgie MeSH
- cékostomie * MeSH
- chirurgická dekomprese metody MeSH
- gastrointestinální endoskopie MeSH
- lidé MeSH
- pseudoobstrukce tlustého střeva * chirurgie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Individuals that band together create new ecological opportunities for microorganisms. In vertical transmission, theory predicts a conserved microbiota within lineages, especially social bees. Bees exhibit solitary to social behavior among and/or within species, while life cycles can be annual or perennial. Bee nests may be used over generations or only once, and foraging ecology varies widely. To assess which traits are associated with bee microbiomes, we analyzed microbial diversity within solitary and social bees of Apidae, Colletidae, and Halictidae, three bee families in Panama's tropical forests. Our analysis considered the microbiome of adult gut contents replicated through time, localities, and seasons (wet and dry) and included bee morphology and comparison to abdominal (dissected) microbiota. Diversity and distribution of tropical bee microbes (TBM) within the corbiculate bee clade were emphasized. RESULTS: We found the eusocial corbiculate bees tended to possess a more conserved gut microbiome, attributable to vertical transmission, but microbial composition varied among closely related species. Euglossine bees (or orchid bees), corbiculates with mainly solitary behavior, had more variable gut microbiomes. Their shorter-tongued and highly seasonal species displayed greater diversity, attributable to flower-visiting habits. Surprisingly, many stingless bees, the oldest corbiculate clade, lacked bacterial genera thought to predate eusociality, while several facultatively social, and solitary bee species possessed those bacterial taxa. Indeed, nearly all bee species displayed a range of affinities for single or multiple variants of the "socially associated" bacterial taxa, which unexpectedly demonstrated high sequence variation. CONCLUSIONS: Taken together, these results call into question whether specific bacterial associates facilitate eusocial behavior, or are subsequently adopted, or indicate frequent horizontal transmission between perennial eusocial colonies and other social, facultatively social, and solitary bees. Video Abstract.
- MeSH
- lesy MeSH
- mikrobiota * genetika MeSH
- sociální chování MeSH
- střevní mikroflóra * genetika MeSH
- včely MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGFβ1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-α, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators. Video Abstract.
BACKGROUND AND AIMS: The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes. METHODS: A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months. RESULTS: Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10-11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR = 1.30 × 10-12), but metabolite clusters were not associated with disease-free survival (p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency (p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7. CONCLUSIONS: Networks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection. Video Abstract.
- MeSH
- chromatografie kapalinová MeSH
- kolorektální nádory * chirurgie MeSH
- lidé MeSH
- mikrobiota * genetika MeSH
- střevní mikroflóra * genetika MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
