We aimed to explore the development and cell communication of osteoblasts and osteoclasts with aneuploidy variation in giant cell tumour of bone (GCTB). We predicted the diploid and aneuploid cells in tissue samples using the CopyKAT package. The Monocle2 package was used to analyse differentiation trajectories of aneuploid cells. We used the CellChat package to observe the signalling pathways and ligand-receptor pairs for the two interaction types, "Cell-Cell Contact" and "Secreted Signalling", respectively. A total of 9,117 cells were obtained including eight cell types. Most aneuploid cells were osteoblasts. As the cell differentiation trajectory matured, we found that aneuploid osteoblasts first increased the inflammatory response activity and then enhanced the ability to activate T cells, whereas osteoclasts gradually enhanced the cellular energy metabolism, cell adhesion, cell proliferation and immune response; the activated biological functions were gradually weakened. The analysis by CellChat indicated that CTLA4 or TIGIT might act as important immune checkpoint genes to attenuate the inhibitory effect of aneuploid osteoclasts on NK/T cells, thereby enhancing the activity of NK/T cells. Our study found that both osteoblasts and osteoclasts might be involved in the development of GCTB, which may provide a new direction for the treatment of GCTB.
- MeSH
- analýza jednotlivých buněk * MeSH
- aneuploidie * MeSH
- buněčná diferenciace genetika MeSH
- lidé MeSH
- mezibuněčná komunikace * genetika MeSH
- nádory kostí genetika patologie metabolismus MeSH
- obrovskobuněčný nádor kosti * genetika patologie MeSH
- osteoblasty * metabolismus MeSH
- osteoklasty * metabolismus patologie MeSH
- sekvenční analýza RNA metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.
- Klíčová slova
- RNA, metastasis, resistance to therapy, small extracellular vesicles, tumour microenvironment,
- MeSH
- extracelulární vezikuly * metabolismus MeSH
- kruhová RNA genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mezibuněčná komunikace MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové mikroprostředí * MeSH
- nádory * patologie genetika metabolismus MeSH
- RNA dlouhá nekódující genetika MeSH
- RNA genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kruhová RNA MeSH
- messenger RNA MeSH
- mikro RNA MeSH
- RNA dlouhá nekódující MeSH
- RNA MeSH
The SorC family is a large group of bacterial transcription regulators involved in controlling carbohydrate catabolism and quorum sensing. SorC proteins consist of a conserved C-terminal effector-binding domain and an N-terminal DNA-binding domain, whose type divides the family into two subfamilies: SorC/DeoR and SorC/CggR. Proteins of the SorC/CggR subfamily are known to regulate the key node of glycolysis-triose phosphate interconversion. On the other hand, SorC/DeoR proteins are involved in a variety of peripheral carbohydrate catabolic pathways and quorum sensing functions, including virulence. Despite the abundance and importance of this family, SorC proteins seem to be on the periphery of scientific interest, which might be caused by the fragmentary information about its representatives. This review aims to compile the existing knowledge and provide material to inspire future questions about the SorC protein family.
- Klíčová slova
- SorC family, bacterial transcription regulation, carbohydrate metabolism, quorum sensing,
- MeSH
- Bacteria metabolismus genetika MeSH
- bakteriální proteiny * metabolismus genetika chemie MeSH
- quorum sensing genetika MeSH
- regulace genové exprese u bakterií MeSH
- transkripční faktory metabolismus genetika chemie MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- bakteriální proteiny * MeSH
- transkripční faktory MeSH
Numerous functions in pathogenic Pectobacterium are regulated by quorum sensing (QS). Two different aiiA genes isolated from Bacillus sp. A24(aiiAA24) and Bacillus sp. DMS133(aiiADMS133) were used. Both genes encode acyl-homoserine lactonase (AiiA), which disrupts QS in Pectobacterium. To investigate the effect of different AiiAs on the inhibition of Pectobacterium carotovorum pathogenicity, two aiiA genes from different Bacillus strains were cloned and the resulting plasmids pME6863 (aiiAA24) and pME7080 (aiiADMS133) were transformed into P. carotovorum EMPCC cells. The effects of different lactonases on virulence features such as enzymatic activity, twitching and swimming motilities, and production of pellicle and biofilm formation were investigated. In EMPCC/pME6863, twitching and swimming motilities, and pellicle production were significantly reduced compared with EMPCC/pME7080. Quantitative real-time PCR (qRT-PCR) was used to measure virulence gene expression in transformed cells compared with expression levels in wild-type EMPCC. The expression of peh and hrpL genes was greatly reduced in EMPCC/pME6863 compared with EMPCC/pME7080. The sequence alignment and molecular dynamic modeling of two different AiiAA24 and AiiADMS133 proteins suggested that the replacement of proline 210 from AiiAA24 to serine in AiiADMS133 caused the reduction of enzyme activity in AiiADMS133.
- Klíčová slova
- Pectobacterium carotovorum, Acyl-homoserine lactone, Molecular dynamic modeling, Quorum sensing, Virulence genes,
- MeSH
- Bacillus * genetika enzymologie MeSH
- bakteriální proteiny * genetika metabolismus MeSH
- biofilmy růst a vývoj MeSH
- karboxylesterhydrolasy * genetika metabolismus MeSH
- klonování DNA MeSH
- metaloendopeptidasy MeSH
- Pectobacterium carotovorum genetika enzymologie patogenita MeSH
- quorum sensing * MeSH
- regulace genové exprese u bakterií MeSH
- virulence MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- AiiA protein, Bacillus MeSH Prohlížeč
- bakteriální proteiny * MeSH
- karboxylesterhydrolasy * MeSH
- metaloendopeptidasy MeSH
- N-acyl homoserine lactonase MeSH Prohlížeč
BACKGROUND: Natural killer cells (NK) and innate lymphoid cells with their subsets (ILC) are part of the innate immune system. OBJECTIVE: The aim is to evaluate how NK cells and ILC cells interact in atopic dermatitis (AD) patients (with and without dupilumab therapy) compared to control group. MATERIALS AND METHODS: Complete dermatological examination was performed in all patients included in the study (19 AD patients with dupilumab, 17 AD patients without dupilumab). Surface molecules expressed on NK cells and ILC cells were analyzed by flow cytometry. The association between NK cells and total ILC cells, ILC-1, ILC-2, ILC-3, NCR+ILC3, NCR-ILC3 were compared in AD patients and in the control group. The non-parametric Spearman's rank correlation coefficient was used for this statistical analysis. We evaluated the association of parameters with AD severity at the time of treatment.Non-parametric Mann-Whitney, Kolmogorov-Smirnov tests were used. RESULTS: We confirmed the higher association between NK cells and total ILC cells in AD patients without dupilumab therapy (in 30.3 %) and in healthy controls (in 27.2 %); this association is low in AD patients with dupilumab therapy (in 0.1 %). The higher association was confirmed between NK cells and ILCs subsets only in AD patients without dupilumab therapy; in these patients the highest association was confirmed between NK cells and ILC-2 cells (in 38.6 %). No statistically significant difference in the count of NK cells and ILC cells was found between mild and moderate form of AD patients treated with dupilumab. CONCLUSION: Targeting these cell types or the cytokines they produce could represent potential therapeutic strategies for controlling inflammation and alleviating symptoms in AD patients.
- Klíčová slova
- Atopic dermatitis, Dupilumab, ILC cells, NK cells,
- MeSH
- atopická dermatitida * farmakoterapie imunologie MeSH
- buňky NK * imunologie účinky léků MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty imunologie účinky léků MeSH
- mezibuněčná komunikace MeSH
- mladý dospělý MeSH
- podskupiny lymfocytů imunologie účinky léků MeSH
- přirozená imunita účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dupilumab MeSH Prohlížeč
- humanizované monoklonální protilátky * MeSH
Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.
- Klíčová slova
- Fibrosis, Gastroenterology, Inflammation, Inflammatory bowel disease, Monocytes,
- MeSH
- Crohnova nemoc * metabolismus patologie imunologie MeSH
- dospělí MeSH
- endopeptidasy metabolismus genetika MeSH
- extracelulární matrix metabolismus patologie MeSH
- fibroblasty * metabolismus patologie MeSH
- fibróza * MeSH
- ileum patologie metabolismus imunologie MeSH
- jaderné proteiny metabolismus genetika MeSH
- lidé MeSH
- mezibuněčná komunikace MeSH
- monocyty * metabolismus patologie imunologie MeSH
- myši MeSH
- receptory buněčného povrchu metabolismus genetika MeSH
- transkripční faktor Twist * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- endopeptidasy MeSH
- jaderné proteiny MeSH
- receptory buněčného povrchu MeSH
- transkripční faktor Twist * MeSH
- TWIST1 protein, human MeSH Prohlížeč
Anodic titanium dioxide (TiO2) nanostructures, i.e., obtained by electrochemical anodization, have excellent control over the nanoscale morphology and have been extensively investigated in biomedical applications owing to their sub-100 nm nanoscale topography range and beneficial effects on biocompatibility and cell interactions. Herein, we obtain TiO2 nanopores (NPs) and nanotubes (NTs) with similar morphologies, namely, 15 nm diameter and 500 nm length, and investigate their characteristics and impact on stem cell adhesion. We show that the transition of TiO2 NPs to NTs occurs via a pore/wall splitting mechanism and the removal of the fluoride-rich layer. Furthermore, in contrast to the case of NPs, we observe increased cell adhesion and proliferation on nanotubes. The enhanced mesenchymal stem cell adhesion/proliferation seems to be related to a 3-fold increase in activated integrin clustering, as confirmed by immunogold labeling with β1 integrin antibody on the nanostructured layers. Moreover, computations of the electric field and surface charge density show increased values at the inner and outer sharp edges of the top surfaces of the NTs, which in turn can influence cell adhesion by increasing the bridging interactions mediated by proteins and molecules in the environment. Collectively, our results indicate that the nanoscale surface architecture of the lateral spacing topography can greatly influence stem cell adhesion on substrates for biomedical applications.
- Klíčová slova
- TiO2 nanopores, TiO2 nanotubes, anodization, integrin, stem cells, surface topography,
- MeSH
- buněčná adheze MeSH
- mezibuněčná komunikace MeSH
- nanopóry * MeSH
- nanotrubičky * chemie MeSH
- povrchové vlastnosti MeSH
- titan chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- titan 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.
- Klíčová slova
- Angiogenesis, Biomarkers, Cancer, Cancer-associated fibroblasts, Cell death, Exosomal proteins, Exosomes, Extracellular vesicles, Immune evasion, Metastasis, Therapy resistance, Tumour microenvironment,
- MeSH
- exozómy * MeSH
- extracelulární vezikuly * MeSH
- lidé MeSH
- mezibuněčná komunikace MeSH
- nádorové mikroprostředí MeSH
- nádory * MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Microorganisms are a repository of interesting metabolites and functions. Therefore, accessing them is an important exercise for advancing not only basic questions about their physiology but also to advance technological applications. In this sense, increasing the culturability of environmental microorganisms remains an important endeavor for modern microbiology. Because microorganisms do not live in isolation in their environments, molecules can be added to the cultivation strategies to "inform them" that they are present in growth-permissive environmental conditions. Signaling molecules such as acyl-homoserine lactones and 3',5'-cyclic adenosine monophosphate belong to the plethora of molecules used by bacteria to communicate with each other in a phenomenon called quorum sensing. Therefore, including quorum sensing molecules can be an incentive for microorganisms, specifically soil bacteria, to increase their numbers on solid media.
- Klíčová slova
- acyl-homoserine lactones, cAMP, increased culturability, non-culturable bacteria, oligotrophic medium, signaling molecules,
- MeSH
- acylbutyrolaktony * metabolismus MeSH
- Bacteria * metabolismus MeSH
- quorum sensing fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acylbutyrolaktony * MeSH
Lactobacillus plantarum NMD-17 separated from koumiss could produce a bacteriocin named plantaricin MX against Gram-positive bacteria and Gram-negative bacteria. The bacteriocin synthesis of L. plantarum NMD-17 was remarkably induced in co-cultivation with Lactobacillus reuteri NMD-86 as the increase of cell numbers and AI-2 activity, and the expressions of luxS encoding signal AI-2 synthetase, plnB encoding histidine protein kinase, plnD encoding response regulator, and plnE and plnF encoding structural genes of bacteriocin were significantly upregulated in co-cultivation, showing that the bacteriocin synthesis of L. plantarum NMD-17 in co-cultivation may be regulated by LuxS/AI-2-mediated quorum sensing system. In order to further demonstrate the role of LuxS/AI-2-mediated quorum sensing system in the bacteriocin synthesis of L. plantarum NMD-17, plasmids pUC18 and pMD18-T simple were used as the skeleton to construct the suicide plasmids pUC18-UF-tet-DF and pMD18-T simple-plnB-tet-plnD for luxS and plnB-plnD gene deletion, respectively. luxS and plnB-plnD gene knockout mutants were successfully obtained by homologous recombination. luxS gene knockout mutant lost its AI-2 synthesis ability, suggesting that LuxS protein encoded by luxS gene is key enzyme for AI-2 synthesis. plnB-plnD gene knockout mutant lost the ability to synthesize bacteriocin against Salmonella typhimurium ATCC14028, indicating that plnB-plnD gene was a necessary gene for bacteriocin synthesis of L. plantarum NMD-17. Bacteriocin synthesis, cell numbers, and AI-2 activity of luxS or plnB-plnD gene knockout mutants in co-cultivation with L. reuteri NMD-86 were obviously lower than those of wild-type strain in co-cultivation at 6-9 h (P < 0.01). The results showed that LuxS/AI-2-mediated quorum sensing system played an important role in the bacteriocin synthesis of L. plantarum NMD-17 in co-cultivation.
- Klíčová slova
- Bacteriocin, Co-cultivation, Gene knockout, Lactobacillus plantarum, LuxS-mediated quorum sensing system,
- MeSH
- bakteriální proteiny metabolismus MeSH
- bakteriociny * metabolismus MeSH
- Lactobacillus plantarum * genetika MeSH
- Lactobacillus fyziologie MeSH
- lidé MeSH
- plazmidy MeSH
- quorum sensing MeSH
- regulace genové exprese u bakterií MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bakteriální proteiny MeSH
- bakteriociny * MeSH