BACKGROUND: Chronic venous disease (CVD) is a common disorder of lower extremities. OBJECTIVES: The study was scheduled to investigate the relationship between polymorphisms in major proinflammatory genes TNF α (-238 A/G; -308 A/G), TNF β (NcoI), IL-1β (+3953 T/C); IL-6 (-174 G/C; -596 G/C) and ADAM17 (3'TACE) and CVD risk. Genotype-phenotype study was calculated to test possible association between examined genotypes and phenotypes of CVD. METHODS: Finally, 150 CVD patients and 227 control subjects were enrolled to the study. Genotypes in proinflammatory gene polymorphisms were identified from isolated DNA by PCR method and restriction analysis. RESULTS: Significant differences in genotype distribution/allelic frequencies in TNF β gene, IL-1 β gene and in ADAM17 gene polymorphisms were found between CVD women and control ones. In the genotype-phenotype study, identified genotypes were associated with arterial hypertension (ADAM17, IL-6-men), ischaemic heart disease (TNF α and β genes), diabetes mellitus (ADAM17-women, TNF β-men), age of CVD onset (TNF α and IL-6), ulceration (ADAM17), duration of ulceration (ADAM17), ulceration recurrence (ADAM17-women), home care necessity (TNF α), varices surgery (TNF α), erysipelas development (ADAM17-men) and tumour development (TNF α). CONCLUSION: Studying of these polymorphisms associations can help us better identify patients at higher risk of developing severe CVD.
- MeSH
- chronická nemoc MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- interleukin-1beta genetika MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus MeSH
- kardiovaskulární nemoci * genetika MeSH
- lidé MeSH
- lymfotoxin-alfa genetika MeSH
- protein ADAM17 genetika MeSH
- TNF-alfa * genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: This study aimed to identify the phytochemical constituents that could target gastric cancer in Kangai injection using a network pharmacology-based approach. METHODS: Protein-protein interactions (PPI), Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted utilizing String and OmicShare tools. In the in vitro experiments, the related mRNA and protein levels were assessed via real-time quantitative polymerase chain reaction and Western blotting, respectively. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. RESULTS: Kangai injection comprises several compounds, which target multiple substrates and pathways related to gastric cancer. The PPI and Gene Ontology analyses revealed that tumor necrosis factor (TNF) was a hub gene. KEGG pathway enrichment analysis indicated that the the TNF pathway was significantly enriched. Kangai injection decreased the mRNA levels of TNFR2, TRAF2, PI3K, AKT, and IκBα and inhibited the phosphorylation of PI3K, AKT, and IκBα phosphorylations. Kangai injection inhibited cell proliferation, while TNFR2 overexpression or treatment with the PI3K activator 740 Y-P partially restored it. CONCLUSION: Kangai injection operates through multiple targets and pathways in gastric cancer, with the TNFR2/PI3K/AKT/NF-κB pathway playing a crucial role in its mechanism against gastric cancer.
- MeSH
- fosfatidylinositol-3-kinasy MeSH
- lidé MeSH
- nádory žaludku * farmakoterapie genetika MeSH
- NFKB inhibitor alfa MeSH
- protoonkogenní proteiny c-akt MeSH
- receptory TNF - typ II MeSH
- síťová farmakologie MeSH
- TNF-alfa genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Preeclampsia is a gestational disorder characterized by hypertension and proteinuria. Excessive release of pro-inflammatory cytokines, particularly tumour necrosis factor-alpha, has been demonstrated to contribute to endothelial activation and poor trophoblast invasion in placental development, resulting in preeclampsia's clinical symptoms. Genetic polymorphisms of tumour necrosis factor-alpha can regulate its production and may play an important role in the pathogenesis of this disease. This study aimed to evaluate the association of five tumour necrosis factor-alpha gene promoter single nucleotide polymorphisms, or their haplotype combinations, with preeclampsia prevalence. This case-control study was conducted on 300 women with preeclampsia and 300 age-matched women with normal pregnancy from Tunisian hospitals. Genotyping of tumour necrosis factor-alpha -1031 T/C, -376 G/A, -308 G/A, -238 G/A, and +489 G/A SNPs was performed on DNA extracted from blood samples using PCR-restriction fragment-length polymorphism analysis. Statistical analysis was performed using the chi-square test. P < 0.01 were considered statistically significant to take into consideration the multiple comparisons. A significantly higher frequency of the minor allele -1031C (p < 0.001) was observed in preeclampsia cases compared to controls. Notably, the -1031C and -376A (CA) haplotype, which correlates with a higher production of TNF-α protein, had a higher incidence in women with preeclampsia (p = 0.0005). Conversely, the TG haplotype had a low frequency in preeclampsia cases compared to controls (p = 0.002) which suggests that it is associated with a reduced incidence of preeclampsia. These results suggest that tumour necrosis factor-alpha polymorphisms, in particular the -1031C/A, and the haplotype CA, contribute to an increased risk of preeclampsia in Tunisian women.
- MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- genotyp * MeSH
- incidence MeSH
- lidé MeSH
- mladý dospělý MeSH
- polymorfismus genetický MeSH
- preeklampsie epidemiologie genetika MeSH
- riziko MeSH
- těhotenství MeSH
- TNF-alfa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Tunisko MeSH
(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.
- MeSH
- diabetes mellitus 2. typu * komplikace genetika chirurgie MeSH
- interleukin-6 metabolismus MeSH
- kardiochirurgické výkony * MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- nemoci koronárních tepen * komplikace genetika chirurgie MeSH
- perikard metabolismus MeSH
- TNF-alfa genetika metabolismus MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Air pollution caused by road traffic has an unfavorable impact on the environment and also on human health. It has previously been shown, that complete gasoline emissions lead to toxic effects in cell models originating from human airways. Here we focused on extractable organic matter (EOM) from particulate matter, collected from gasoline emissions from fuels with different ethanol content. We performed cytotoxicity evaluation, quantification of mucin and extracellular reactive oxygen species (ROS) production, DNA breaks detection, and selected gene deregulation analysis, after one and five days of exposure of human bronchial epithelial model (BEAS-2B) and a 3D model of the human airway (MucilAirTM). Our data suggest that the longer exposure had more pronounced effects on the parameters of cytotoxicity and mucin production, while the impacts on ROS generation and DNA integrity were limited. In both cell models the expression of CYP1A1 was induced, regardless of the exposure period or EOM tested. Several other genes, including FMO2, IL1A, or TNF, were deregulated depending on the exposure time. In conclusion, ethanol content in the fuels did not significantly impact the toxicity of EOM. Biological effects were mostly linked to xenobiotics metabolism and inflammatory response. BEAS-2B cells were more sensitive to the treatment.
- MeSH
- benzin * MeSH
- bronchy cytologie MeSH
- buněčné linie MeSH
- cytochrom P-450 CYP1A1 genetika MeSH
- epitelové buňky účinky léků metabolismus MeSH
- histony metabolismus MeSH
- interleukin-1alfa genetika MeSH
- látky znečišťující vzduch toxicita MeSH
- lidé MeSH
- oxygenasy genetika MeSH
- pevné částice toxicita MeSH
- reaktivní formy kyslíku metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- TNF-alfa genetika MeSH
- výfukové emise vozidel toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO3)2 NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines, such as tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 (TGFβ1), interleukin 6(IL-6), IL-1α and IL-1β , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.
- MeSH
- aktiny agonisté genetika imunologie MeSH
- alveolární makrofágy účinky léků imunologie patologie MeSH
- aplikace inhalační MeSH
- biologická dostupnost MeSH
- dusičnany farmakokinetika toxicita MeSH
- exprese genu MeSH
- inhalační expozice analýza MeSH
- interleukin-1alfa agonisté genetika imunologie MeSH
- interleukin-1beta agonisté genetika imunologie MeSH
- interleukin-6 agonisté genetika imunologie MeSH
- játra účinky léků imunologie patologie MeSH
- kovové nanočástice aplikace a dávkování toxicita MeSH
- látky znečišťující vzduch farmakokinetika toxicita MeSH
- myši inbrední ICR MeSH
- myši MeSH
- NF-kappa B agonisté genetika imunologie MeSH
- olovo farmakokinetika toxicita MeSH
- plíce účinky léků imunologie patologie MeSH
- poločas MeSH
- spektrofotometrie atomová MeSH
- tkáňová distribuce MeSH
- TNF-alfa agonisté genetika imunologie MeSH
- transformující růstový faktor beta1 agonisté genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Hot water extract from biomass of heterotrophic mutant green alga Parachlorella kessleri HY1 (Chlorellaceae) was deproteinised, and three polysaccharidic fractions were obtained by preparative chromatography. The low-molecular fraction (1.5 × 104g mol-1) was defined mainly as branched O-2-β-xylo-(1→3)-β-galactofuranan where xylose is partially methylated at O-4. Two high-molecular fractions (3.05 × 105 and 9.84 × 104g mol-1) were complex polysaccharides containing α-l-rhamnan and xylogalactofuranan parts in different ratios. The polysaccharides were well soluble in hot water and, upon cooling, tended to self-segregate. Immunomodulatory activities of the obtained fractions were preliminary tested using ELISA, FACS and ImmunoSpot kits. The polysaccharides increased the TNF-α production in melanoma bearing mice with much higher intensity than in healthy mice. This was in agreement with the FACS results on T and B cells indicating their possibly secondary activation by innate immunity cells.
- MeSH
- B-lymfocyty účinky léků imunologie patologie MeSH
- CD antigeny genetika imunologie MeSH
- Chlorophyta chemie MeSH
- imunologické faktory chemie izolace a purifikace farmakologie MeSH
- interferon gama genetika imunologie MeSH
- interleukin-2 genetika imunologie MeSH
- interleukin-4 genetika imunologie MeSH
- lipopolysacharidy antagonisté a inhibitory farmakologie MeSH
- melanom imunologie patologie MeSH
- metylace MeSH
- molekulová hmotnost MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory kůže imunologie patologie MeSH
- polysacharidy chemie izolace a purifikace farmakologie MeSH
- primární buněčná kultura MeSH
- regulace genové exprese účinky léků MeSH
- rostlinné extrakty chemie MeSH
- rozpustnost MeSH
- sacharidové sekvence MeSH
- T-lymfocyty účinky léků imunologie patologie MeSH
- TNF-alfa genetika imunologie MeSH
- voda MeSH
- xylosa chemie izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2.
- MeSH
- buněčné linie MeSH
- epitelové buňky účinky léků imunologie metabolismus MeSH
- interleukin-1 genetika MeSH
- interleukin-6 genetika MeSH
- MAP kinasový signální systém účinky léků genetika imunologie MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus MeSH
- prasata MeSH
- střevní sliznice účinky léků imunologie metabolismus MeSH
- TNF-alfa genetika MeSH
- transkriptom účinky léků MeSH
- trichotheceny toxicita MeSH
- viabilita buněk účinky léků MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In mammals, leptin and tumor-necrosis factor (TNF) are prominent interacting adipokines mediating appetite control and insulin sensitivity. While TNF pleiotropically functions in immune defense and cell survival, leptin is largely confined to signaling energy stores in adipocytes. Knowledge about the function of avian leptin and TNF is limited and they are absent or lowly expressed in adipose, respectively. Employing radiation-hybrid mapping and FISH-TSA, we mapped TNF and its syntenic genes to chicken chromosome 16 within the major histocompatibility complex (MHC) region. This mapping position suggests that avian TNF has a role in regulating immune response. To test its possible interaction with leptin within the immune system and beyond, we compared the transcription patterns of TNF, leptin and their cognate receptors obtained by meta-analysis of GenBank RNA-seq data. While expression of leptin and its receptor (LEPR) were detected in the brain and digestive tract, TNF and its receptor mRNAs were primarily found in viral-infected and LPS-treated leukocytes. We confirmed leptin expression in the duodenum by immunohistochemistry staining. Altogether, we suggest that whereas leptin and TNF interact as adipokines in mammals, in birds, they have distinct roles. Thus, the interaction between leptin and TNF may be unique to mammals.
- MeSH
- buněčné linie MeSH
- duodenum metabolismus MeSH
- kur domácí genetika metabolismus MeSH
- leptin genetika metabolismus MeSH
- leptinové receptory metabolismus MeSH
- mapování chromozomů * MeSH
- mapování pomocí radiačních hybridů MeSH
- messenger RNA genetika metabolismus MeSH
- metafáze genetika MeSH
- receptory TNF genetika metabolismus MeSH
- regulace genové exprese * MeSH
- savci genetika MeSH
- signální transdukce * MeSH
- syntenie genetika MeSH
- TNF-alfa genetika metabolismus MeSH
- trávení * MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Východiska: Bylo provedeno několik studií týkajících se souvislosti TNF-alpha; -308G>A s rizikem karcinomu děložního čípku (cervical cancer - CC) a prsu (breast cancer - BC). Nicméně jejich závěry nebyly konzistentní. Proto jsme provedli komplexní metaanalýzu, aby bylo možné souvislost shodněji zhodnotit ze všech příslušných případových kontrolních studiích. Metody: Do 1. února 2019 jsme systematicky prohledali PubMed, Google Scholar a databázi Cochrane Library. Míra rizika (OR) s 95% intervalem spolehlivosti (CI) byla vypočtena pomocí modelu s pevnými nebo náhodnými efekty. Výsledky: V této metaanalýze bylo vybráno celkem 40 případových studií zahrnujících 20 studií s 4 780 případy a 4 620 kontrolami na CC a 20 studií s 12 390 případy a 14 910 kontrolami na BC. Souhrnné výsledky ukázaly, že TNF-alpha; -308G>A polymorfizmus byl významně spojen se zvýšeným rizikem CC (A vs. G: OR 1,277; 95% CI 1,104 - 1,477; p = 0,001; OR 1,333; 95% CI 1,062 - 1,674; p = 0,013; AG vs. GG: OR 1,307; 95% CI 1,064 - 1,605; p = 0,011 a AA + AG vs. GG: 95% CI 1,104 - 1,587; p = 0,002) a BC (AA vs. AG + GG: OR 0,094; 95% CI 0,058-0,152, p ≤ 0,001). Ve stratifikovaných analýzách podle etnicity byl polymorfizmus TNF-alpha; -308G>A významně spojen s rizikem CC (u kavkazské a africké populace) a BC (u bělochů a Asiatů). Závěr: Naše výsledky ukázaly, že polymorfizmus TNF-alpha; -308G>A může být rizikovým faktorem karcinomu děložního čípku a BC v závislosti na etnicitě.
Background: To date, several studies have been carried out on the association of TNF-α -308G>A with the risk of cervical cancer (CC) and breast cancer (BC). However, their conclusions were not consistent. Thus, we performed a comprehensive meta-analysis to evaluate the association more precisely from all eligible case-control studies. Methods: We searched the PubMed, Google Scholar and Cochrane Library databases systematically to identify relevant studies up to 1 February 2019. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using a fixed- or random-effects model. Results: A total of 40 case-control studies including 20 studies with 4,780 cases and 4,620 controls on CC and 20 studies with 12,390 cases and 14,910 controls on BC were selected in this meta-analysis. The pooled results showed that the TNF-α -308G>A polymorphism was significantly associated with an increased risk of CC (A vs. G: OR 1.277; 95% CI 1.104–1.477; P = 0.001; AA vs. GG: OR 1.333; 95% CI 1.062–1.674; P = 0.013; AG vs. GG: OR 1.307; 95% CI 1.064–1.605; P = 0.011; and AA + AG vs. GG: OR 1.324; 95% CI 1.104–1.587; P = 0.002) and BC (AA vs. AG + GG: OR 0.094; 95% CI 0.058–0.152; P ≤ 0.001). In the stratified analyses by ethnicity, the TNF-α -308G>A polymorphism was signifi cantly associated with the risk of CC (in Caucasians and Africans) and BC (Caucasians and Asians). Conclusion: Our findings showed that TNF-α -308G>A polymorphism may be a risk factor for cervical cancer and breast cancer overall and by ethnicity.
