We analyzed gene expression in THP-1 cells exposed to metal-based nanomaterials (NMs) [TiO2 (NM-100), ZnO (NM-110), SiO2 (NM-200), Ag (NM-300 K)]. A functional enrichment analysis of the significant differentially expressed genes (DEGs) identified the key modulated biological processes and pathways. DEGs were used to construct protein-protein interaction networks. NM-110 and NM-300 K induced changes in the expression of genes involved in oxidative and genotoxic stress, immune response, alterations of cell cycle, detoxification of metal ions and regulation of redox-sensitive pathways. Both NMs shared a number of highly connected protein nodes (hubs) including CXCL8, ATF3, HMOX1, and IL1B. NM-200 induced limited transcriptional changes, mostly related to the immune response; however, several hubs (CXCL8, ATF3) were identical with NM-110 and NM-300 K. No effects of NM-100 were observed. Overall, soluble nanomaterials NM-110 and NM-300 K exerted a wide variety of toxic effects, while insoluble NM-200 induced immunotoxicity; NM-100 caused no detectable changes on the gene expression level.
- MeSH
- hemoxygenasa-1 MeSH
- interleukin-8 metabolismus genetika MeSH
- kovové nanočástice toxicita MeSH
- lidé MeSH
- mapy interakcí proteinů * účinky léků MeSH
- nanostruktury toxicita MeSH
- oxid křemičitý toxicita MeSH
- oxid zinečnatý toxicita chemie MeSH
- stříbro * toxicita MeSH
- THP-1 buňky MeSH
- titan * toxicita MeSH
- transkripční faktor ATF3 genetika metabolismus MeSH
- transkriptom účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The initial phase of multiple sclerosis (MS), often known as clinically isolated syndrome (CIS), is a critical period for identifying individuals at high risk of progressing to full-blown MS and initiating timely treatment. In this study, we aimed to evaluate the prognostic value of C-X-C motif chemokine ligand 13 (CXCL13) and interleukin-8 (IL-8) as potential markers for CIS patients' conversion to MS. Our study encompassed patients with CIS, those with relapsing-remitting MS (RRMS), and control subjects, with sample analysis conducted on both cerebrospinal fluid (CSF) and serum. Patients were categorized into four groups: CIS-CIS (no MS development within 2 years), CIS-RRMS (conversion to RRMS within 2 years), RRMS (already diagnosed), and a control group (CG) with noninflammatory central nervous system disorders. Results showed significantly elevated levels of CXCL13 in CSF across all patient groups compared with the CG (p < 0.0001, Kruskal-Wallis test). Although CXCL13 concentrations were slightly higher in the CIS-RRMS group, statistical significance was not reached. Similarly, significantly higher levels of IL-8 were detected in CSF samples from all patient groups compared with the CG (p < 0.0001, Kruskal-Wallis test). Receiver operating characteristic analysis in the CIS-RRMS group identified both CXCL13 (area under receiver operating characteristic curve = .959) and IL-8 (area under receiver operating characteristic curve = .939) in CSF as significant predictors of CIS to RRMS conversion. In conclusion, our study suggests a trend towards elevated CSF IL-8 and CSF CXCL13 levels in CIS patients progressing to RRMS. These findings emphasize the importance of identifying prognostic markers to guide appropriate treatment strategies for individuals in the early stages of MS.
- MeSH
- biologické markery mozkomíšní mok krev MeSH
- chemokin CXCL13 * mozkomíšní mok krev MeSH
- demyelinizační nemoci mozkomíšní mok MeSH
- dospělí MeSH
- interleukin-8 * mozkomíšní mok krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- prognóza MeSH
- progrese nemoci * MeSH
- relabující-remitující roztroušená skleróza * mozkomíšní mok krev diagnóza MeSH
- roztroušená skleróza mozkomíšní mok krev diagnóza 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
OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.
- MeSH
- antiflogistika terapeutické užití farmakologie MeSH
- chlorhexidin terapeutické užití farmakologie analogy a deriváty MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- faktor 2 související s NF-E2 MeSH
- fibroblasty * účinky léků MeSH
- gingiva * účinky léků MeSH
- gingivitida * farmakoterapie MeSH
- hemoxygenasa-1 MeSH
- interleukin-6 analýza MeSH
- interleukin-8 účinky léků MeSH
- kanabidiol * farmakologie terapeutické užití MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- parodontitida farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
To reveal the variation of gut microbiota and its association with immune function in cured patients with coronavirus 2019 (COVID-19) disease, gut microbiota of patients discharged from hospital for 20 ~ 23 months and healthy volunteers was analyzed by high throughput 16S rRNA sequencing. The diversity and abundance were compared, and the correlation with immunity factors was investigated, and changes in the content of 6 genera microorganisms with proportion higher than 0.1% were revealed in patients with COVID-19 disease: reduced content of Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group and increased content of Hungatella. NK cells were negatively correlated to Subdoligranulum, while CD8 cells were positively correlated to Subdoligranulum but negative to Hungatella. IL-8 concentration was negatively correlated to Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group but positively to Hungatella, while IL-1β concentration was negatively correlated to Haemophilus and Eubacterium ventriosum group but positively to Hungatella. The variation of probiotics and potential pathogenic bacteria implies a higher risk in diseases and inflammation, and the modulation of the gut microbiota may help the healing of COVID-19 patients.
- MeSH
- Bacteria klasifikace genetika izolace a purifikace MeSH
- buňky NK imunologie MeSH
- COVID-19 * imunologie mikrobiologie MeSH
- dospělí MeSH
- feces mikrobiologie virologie MeSH
- interleukin-1beta MeSH
- interleukin-8 MeSH
- lidé středního věku MeSH
- lidé MeSH
- RNA ribozomální 16S * genetika MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- střevní mikroflóra * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Interleukin (IL)-40 is a new cytokine related to immune system function and malignancies. Recently, an association of IL-40 with rheumatoid arthritis (RA) and externalisation of neutrophil extracellular traps (NETosis) was found. As neutrophils are implicated in RA development, we investigated IL-40 in early stages of RA (ERA). METHODS: IL-40 was determined in serum of treatment naïve patients with ERA at baseline (n=60) and 3 months after initiation of conventional therapy and in healthy controls (HC; n=60). Levels of IL-40, cytokines and NETosis markers were measured by ELISA. NETosis was visualised by immunofluorescence. In vitro experiments were performed on peripheral blood neutrophils from ERA patients (n=14). Cell-free DNA was analysed in serum and supernatants. RESULTS: Serum IL-40 was elevated in ERA compared with HC (p<0.0001) and normalised after 3 months of therapy (p<0.0001). Baseline serum IL-40 correlated with rheumatoid factor (IgM) (p<0.01), anti-cyclic citrullinated peptide (p<0.01) autoantibodies and NETosis markers (proteinase 3; neutrophil elastase (NE); myeloperoxidase) (p<0.0001). Levels of NE significantly decreased after therapy (p<0.01) and correlated with the decrease of serum IL-40 (p<0.05). In vitro, neutrophils enhanced IL-40 secretion following NETosis induction (p<0.001) or after exposure to IL-1β, IL-8 (p<0.05), tumour necrosis factor or lipopolysaccharide (p<0.01). Recombinant IL-40 up-regulated IL-1β, IL-6 and IL-8 (p<0.05 for all) in vitro. CONCLUSION: We showed that IL-40 is significantly up-regulated in seropositive ERA and decreases after conventional therapy. Moreover, neutrophils are an important source of IL-40 in RA, and its release is potentiated by cytokines and NETosis. Thus, IL-40 may play a role in ERA.
- MeSH
- autoprotilátky MeSH
- cytokiny MeSH
- interleukin-8 MeSH
- interleukiny MeSH
- lidé MeSH
- neutrofily * MeSH
- revmatoidní artritida * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The pathophysiological processes leading to epileptogenesis and pharmacoresistance in epilepsy have been the subject of extensive preclinical and clinical research. The main impact on clinical practice is the development of new targeted therapies for epilepsy. We studied the importance of neuroinflammation in the development of epileptogenesis and pharmacoresistance in childhood epilepsy patients. METHODS: A cross-sectional study conducted at two epilepsy centers in the Czech Republic compared 22 pharmacoresistant patients and 4 pharmacodependent patients to 9 controls. We analyzed the ProcartaPlexTM 9-Plex immunoassay panel consisting of interleukin (IL)-6, IL-8, IL-10, IL-18, CXCL10/IP-10, monocyte chemoattractant protein 1 (CCL2/MCP-1), B lymphocyte chemoattractant (BLC), tumor necrosis factor-alpha (TNF-α), and chemokine (C-X3-X motif) ligand 1 (fractalkine/CXC3CL1) to determine their alterations in cerebrospinal fluid (CSF) and blood plasma, concurrently. RESULTS: The analysis of 21 paired CSF and plasma samples in pharmacoresistant patients compared to controls revealed a significant elevation of CCL2/MCP-1 in CSF (p < 0.000512) and plasma (p < 0.00.017). Higher levels of fractalkine/CXC3CL1 were revealed in the plasma of pharmacoresistant patients than in controls (p < 0.0704), and we determined an upward trend in CSF IL-8 levels (p < 0.08). No significant differences in CSF and plasma levels were detected between pharmacodependent patients and controls. CONCLUSION: Elevated CCL2/MCP-1 in CSF and plasma, elevated levels of fractalkine/CXC3CL1 in CSF, and a trend toward elevated IL-8 in the CSF of patients with pharmacoresistant epilepsy indicate these cytokines as potential biomarkers of epileptogenesis and pharmacoresistance. CCL2/MCP-1was detected in blood plasma; this assessment may be easily achieved in clinical practice without the invasiveness of a spinal tap. However, due to the complexity of neuroinflammation in epilepsy, further studies are warranted to confirm our findings.
The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.
IL-8 and its polymorphisms are involved in multiple acute and chronic inflammatory processes including pathological changes to surrounding structures of the teeth called periodontal diseases or periodontitis. The aim of this manuscript was to systematically review studies from 2006 to 2021 on IL-8 polymorphisms and their association with periodontitis. Literature analysis was done following the PRISMA protocol guidance using articles not older than 15 years (2006-2021). The search was carried out using PubMed (MEDLINE), ScienceDirect and Wiley Online Library databases. For the focus question, the PICO (population (P), intervention (I), control (C), and outcome (O)) study design protocol was used, and the following question was formulated: are IL-8 gene polymorphisms associated with periodontitis? A total of 2422 articles were found at the beginning of the search. After applying the inclusion and exclusion criteria, screening, and full-text article exclusion with reasons, 31 studies were included in the analysis. In conclusion, IL-8 and its gene polymorphisms are associated with an increased risk of periodontal diseases.
- MeSH
- chronická parodontitida * MeSH
- interleukin-8 genetika MeSH
- lidé MeSH
- parodontitida * genetika MeSH
- polymorfismus genetický MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Background: Interleukin-18 (IL-18) belongs to the cytokine family IL-1. IL-18 is synthesized as inactive precursors which need to be processed into an active interleukin by the Caspase-1 enzyme. The role of IL-18 is implicated in several auto-immune disorders, myocardial function, emphysema, metabolic syndromes, psoriasis, bowel inflammation, sepsis, and acute kidney injury. IL-18 exhibits pro-inflammatory properties, such as increased cell adhesion molecules, nitric oxide production, enhancement of T-cell and natural killer cell maturation, and increasing the production of chemokines. This study was designed from November 2020 to February 2021 at Al-Shomali hospital, Babylon governorate, Iraq. This study aimed to assess the levels of IL-18 in patients with PCOS, T2DM and CAD before treatment with metformin and after metformin medication, and to evaluate the roles of IL-18 in the development of this disease. Materials and methods: The study design is a case-control study and patients are selected by simple randomization after diagnosis by a specialist based on clinical diagnosis and laboratory findings. An enzyme-linked immunosorbent test (ELISA) was used to estimate the level of serum IL-18 before and after metformin administration. A total of 300 patients were involved in this study, divided according to their chronic illness as 60 women with PCOS, 60 patients Type 2 diabetes mellitus (T2DM), 60 patients with myocardial infarction (MI), and 60 patients with T2DM and MI. In addition, 30 healthy people as a control group. Results: Before treatment with metformin, the results were exhibited a significant difference (P≤0.0001) in the concentrations of IL-18 in PCOS, T2DM, and patients with CAD as compared with control. While, after metformin treatment, a significant decrease (P≤0. 01, P≤0.0001 and P≤0.001) in IL-18 level in patients with PCOS and T2DM and CAD respectively as compared to before metformin treatment. Conclusion: Metformin administration reduces the inflammatory events of IL-18 in patients with T2DM and CAD and PCOS.
Východiska: Dříve provedené studie hodnotily souvislost polymorfizmu IL-8 -251T>A a IL-18 -607C>A s rizikem karcinomu prsu v různých populacích, ale výsledky zůstávají nekonzistentní a neprůkazné. Provedli jsme tedy tuto metaanalýzu s cílem prozkoumat souvislosti. Metody: Komplexní vyhledávání literatury v databázích PubMed, EMBASE, Web of Science, Scopus, SciELO, SID, and CNKI z hlediska všech vhodných studií publikovaných do 1. října 2020. Pro hodnocení intenzity souvislosti byly použity souhrnné poměry šancí (odds ratio – OR) s 95% intervaly spolehlivosti (confidence interval – CI). Výsledky: Bylo vybráno celkem 12 studií případů a kontrol o polymorfizmu IL-8 -251T>A vč. 7 studií s 2 370 případy a 2 314 kontrolami a 5 studií o polymorfizmu IL-18 -607C>A s 900 případy a 882 kontrolami. Souhrnná data ukázala, že polymorfizmy IL-8 -251T>A (AT vs. TT: OR = 1,187; 95% CI 1,038–1,356; p = 0,012) a IL-18 -607C>A (A vs. T: OR = 1,205; 95% CI 1,055–1,377; p = 0,006; AA vs. TT: OR = 1,379; 95% CI 1,056–1,802; p = 0,018; a AA vs. AT+TT: OR = 1,329; 95% CI 1,053–1,678; p = 0,017) měly obecně souvislost se zvýšeným rizikem karcinomu prsu. Navíc když byly studie stratifikovány podle etnik, u IL-8 -251T>A byla významná souvislost s rizikem karcinomu prsu u Afričanek. Testy publikačního zkreslení u metaanalýzy žádné publikační zkreslení neprokázaly. Závěr: Tato metaanalýza odhalila, že polymorfizmus IL-8 -251T>A a IL-18 -607C>A je spojen s náchylností ke karcinomu prsu. Pro lepší vyhodnocení těchto asociací je ovšem třeba dalších multicentrických studií s různými etniky.
Background: Previous studies have evaluated the association of IL-8 -251T>A and IL-18 -607C>A polymorphisms with a risk of breast cancer in different populations, but the results remain inconsistent and inconclusive. Thus, we performed this meta-analysis to explore the associations. Methods: A comprehensive literature search in PubMed, EMBASE, Web of Science, Scopus, SciELO, SID, and CNKI for all eligible studies published up to October 1, 2020. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the intensity of associations. Results: A total of 12 case-control studies including seven studies with 2,370 cases and 2,314 controls on IL-8 -251T>A, and five studies with 900 cases and 882 controls on IL-18 -607C>A polymorphism were selected. Pooled data showed that IL-8 -251T>A (AT vs. TT: OR= 1.187; 95% CI 1.038–1.356; P = 0.012) and IL-18 -607C>A polymorphisms (A vs. T: OR = 1.205; 95% CI 1.055–1.377; P = 0.006; AA vs. TT: OR = 1.379; 95% CI 1.056–1.802; P = 018; and AA vs. AT+TT: OR = 1.329; 95% CI 1.053–1.678; P = 0.017) were associated with increased risk of breast cancer in overall. Moreover, when the studies were stratified by ethnicity, the IL-8 -251T>A was significantly associated with breast cancer risk in Africans. Publication bias tests provide no evidence of presence of publication bias in a meta-analysis. Conclusion: This meta-analysis results revealed that the IL-8 -251T>A and IL-18 -607C>A polymorphisms are associated with susceptibility to breast cancer. However, further multicenter studies with larger sample sizes in different ethnicities are required to make a better assessment of these associations.
