OBJECTIVES: To prospectively validate the diagnostic performance of a non-invasive point-of-care tool (Rapid IAI System), including vaginal alpha-fetoprotein and interleukin-6, to predict the occurrence of intra-amniotic inflammation in a Spanish cohort of patients admitted with a diagnosis of preterm labor and intact membranes. METHODS: From 2017 to 2022, we prospectively evaluated a cohort of pregnant women diagnosed with preterm labor and intact membranes admitted below 34+0 weeks who underwent amniocentesis to rule-in/out intra-amniotic infection and/or inflammation. Vaginal sampling was performed at the time of amniocentesis or within 24-48 h. Amniotic fluid IL-6, vaginal alpha-fetoprotein and vaginal IL-6 concentrations were measured using a point-of-care tool provided by Hologic Inc., "Rapid IAI System". We defined intra-amniotic inflammation when amniotic fluid IL-6 values were greater than 11.3 ng/mL. During recruitment, clinicians were blinded to the results of the point-of-care tool. The original prediction model proposed by Hologic Inc. to predict intra-amniotic inflammation was validated in this cohort of patients. RESULTS: We included 151 patients diagnosed with preterm labor and intact membranes. Among these, 29 (19.2 %) had intra-amniotic inflammation. The algorithm including vaginal IL-6 and alpha-fetoprotein showed an area under curve to predict intra-amniotic inflammation of 80.3 % (±5.3 %) with a sensitivity of 72.4 %, specificity of 84.6 %, positive predictive valuve (PPV) of 52.5 %, negative predictive value (NPV) of 92.9 %, and a positive likelihood ratio (LR+) of 4.6 and negative likelihood ratio (LR-) of 0.33. CONCLUSIONS: External validation of a non-invasive rapid point-of-care tool, including vaginal alpha-fetoprotein and IL-6, showed very good diagnostic performance for predicting the absence of intra-amniotic inflammation in women with preterm labor and intact membranes.
- MeSH
- alfa-fetoproteiny * analýza metabolismus MeSH
- amniocentéza metody MeSH
- chorioamnionitida * diagnóza MeSH
- dospělí MeSH
- hodnocení rizik metody MeSH
- interleukin-6 * analýza krev metabolismus MeSH
- lidé MeSH
- plodová voda * metabolismus chemie MeSH
- point of care testing MeSH
- předčasná porodní činnost * diagnóza MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- vagina metabolismus MeSH
- vyšetření u lůžka MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
Numerous studies have reported that increased interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6) levels induce inflammatory conditions. However, the exact mechanisms by which IL-6 drives inflammatory conditions remain unclear. Therefore, we investigated the potential role of IL-6/sIL-6R in inducing energy metabolism, including glycolysis, oxidative phosphorylation, lactate secretion and Akt/mTOR phosphorylation, in Jurkat cells, and whether IL-6 would increase the risk of developing inflammatory conditions due to the high metabolic profile of the T cells. Jurkat CD4 T-cell lines were stimulated with IL-6/sIL-6R for 24 h prior to 48-h stimulation with anti-CD3/CD28. Lactate secretion, glycolysis and oxidative phosphorylation levels were characterized using the Seahorse XF analyser. The Akt and mTOR phosphorylation status was detected using Western blotting. IL-6/sIL-6R significantly induced glycolysis and oxidative phosphorylation and their related parameters, including glycolytic capacity and maximal respiration, followed by significantly increased lactate secretion. Akt and mTOR phosphorylation were increased, which could have resulted from energy metabolism. Here we show that IL-6 enhanced the metabolic profile of Jurkat cells. This effect could have consequences for the metabolism-related signalling pathways, including Akt and mTOR, suggesting that IL-6 might promote T-cell energy metabolism, where T-cell hyperactivity might increase the inflammatory disease risk. The findings should be validated using studies on primary cells isolated from humans.
- MeSH
- energetický metabolismus * účinky léků MeSH
- fosforylace účinky léků MeSH
- glykolýza účinky léků MeSH
- interleukin-6 * metabolismus MeSH
- Jurkat buňky MeSH
- kyselina mléčná metabolismus MeSH
- lidé MeSH
- oxidativní fosforylace účinky léků MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- signální transdukce * účinky léků MeSH
- TOR serin-threoninkinasy * metabolismus MeSH
- zánět * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- mirikizumab,
- MeSH
- cílená molekulární terapie metody MeSH
- dospělí MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- interleukin-23 * antagonisté a inhibitory terapeutické užití MeSH
- kombinovaná farmakoterapie metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- ulcerózní kolitida * diagnostické zobrazování diagnóza farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The etiology of bone loss in celiac disease (CeD) remains a clinical challenge, with uncertainties present such as the extent of involvement of malabsorption and inflammation-induced osteoresorption processes in development of osteopenia/osteoporosis (OPN/OP), or reasons for failure to achieve healthy bone mass (BMD) even after long-term gluten-free diet (GFD) treatment. This observational prospective study explores the in vitro osteoclastogenic potential of peripheral blood precursors originating from adult active (newly diagnosed and untreated) celiac disease patients (aCeD) and describes the longitudinal changes in osteoclastogenesis after long-term adherence to GFD. To find connections between in vitro observations and in vivo bone metabolism changes, serum levels of 25(OH)D3, PTH, bCTX, PINP, CRP, IL-6, RANKL and OPG were measured before and after GFD and levels of these markers were correlated with the rate of osteoclastogenesis in vitro. OPG and IL-6 showed associations with BMD and/or presence of OPN/OP. Patients after GFD (CeD-GFD) exhibited improved BMD and increased serum 25(OH)D3 levels, alongside reduced bCTX and PINP levels. Compared to healthy donors, aCeD osteoclast genesis in vitro was higher and, surprisingly, remained elevated even in CeD-GFD patients. Negative correlation was found between osteoclastogenesis rate and serum OPG in aCeD, while osteoclastogenesis rate positively correlated with PTH in CeD-GFD. These results highlight OPG as marker for risk of OPN/OP in CeD and suggest that improvement of BMD after GFD is a result of uncoupling between bone metabolism and osteoresorptive action of osteoclasts after GFD.
- MeSH
- bezlepková dieta * MeSH
- celiakie * dietoterapie metabolismus MeSH
- dospělí MeSH
- interleukin-6 * krev metabolismus MeSH
- kostní denzita MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteogeneze MeSH
- osteoklasty metabolismus MeSH
- osteoporóza etiologie metabolismus MeSH
- osteoprotegerin * krev metabolismus MeSH
- prospektivní studie MeSH
- vitamin D krev aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
INTRODUCTION: A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO2) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes. METHODS: Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO2 (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO2 (co-exposure model), (b) prior activation with TiO2 alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO2-treated monocytes into macrophages and their polarization were also assessed. RESULTS: The selected TiO2 concentration range (30-120 μg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO2 promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO2 boosted NLRP3 activity, co-exposure to LPS and TiO2 inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO2 on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants. CONCLUSION: This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie MeSH
- buněčná diferenciace účinky léků MeSH
- cytokiny metabolismus MeSH
- inflamasomy účinky léků MeSH
- interleukin-10 metabolismus MeSH
- interleukin-1beta metabolismus MeSH
- kovové nanočástice chemie toxicita MeSH
- kultivované buňky MeSH
- lidé MeSH
- lipopolysacharidy * farmakologie MeSH
- makrofágy účinky léků MeSH
- monocyty * účinky léků MeSH
- nanočástice chemie toxicita MeSH
- protein NLRP3 * metabolismus MeSH
- titan * chemie farmakologie toxicita MeSH
- viabilita buněk * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and serum as a marker of neuronal damage may be a potential biomarker of neuropsychiatric involvement in SLE (NPSLE). METHODS: 80 patients with SLE were included.We obtained paired serum and CSF samples from 48 patients (NPSLE n=32, non-NPSLE n=16) and 31 controls. The serum and CSF levels of NfL were determined using ELISA. RESULTS: Patients with NPSLE demonstrated significantly higher levels of serum NfL compared with the non-NPSLE group (mean 31.68±36.63 pg/mL vs mean 16.75±12.48 pg/mL, respectively, p<0.05) and with controls (mean 10.74±4.36 pg/mL, p<0.01). Notably, CSF NfL concentrations in patients with NPSLE showed an upward trend (mean 1600±2852 pg/mL) in contrast to non-NPSLE patients (mean 393.4±191.9 pg/mL) and controls (mean 509.7±358.5 pg/mL). Furthermore, a positive correlation was observed between serum and CSF NfL levels in patients with NPSLE (R=0.8686, p<0.01). Elevated serum triacylglycerol concentrations, C reactive protein and organ damage were linked to increased serum (p=0.002; p<0.001; p=0.036) and CSF (p=0.008; p=0.007; p<0.001) NfL concentrations. In addition, we established a significant correlation between intrathecal NfL concentrations and interleukin-6 levels in the CSF of patients with NPSLE (R=0.5118, p<0.05). CONCLUSION: The serum NfL levels may be a readily available marker of neuropsychiatric involvement in SLE.
- MeSH
- biologické markery * krev mozkomíšní mok MeSH
- dospělí MeSH
- ELISA MeSH
- interleukin-6 krev mozkomíšní mok MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- neurofilamentové proteiny * krev mozkomíšní mok MeSH
- průřezové studie MeSH
- studie případů a kontrol MeSH
- vaskulitida centrálního nervového systému při lupus erythematodes * krev mozkomíšní mok 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
- MeSH
- interleukin-6 analýza krev MeSH
- kazuistiky jako téma MeSH
- lidé MeSH
- multiorgánové selhání diagnostické zobrazování diagnóza klasifikace patologie MeSH
- novorozenec s extrémně nízkou porodní hmotností MeSH
- novorozenec MeSH
- syndrom systémové zánětlivé reakce * diagnóza etiologie komplikace MeSH
- ultrasonografie prenatální metody MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of naïve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion. Intrathecal application of the CXCR4 inhibitor AMD3100 following CSNT reduced CXCL12 and CXCR4 protein levels in cervical DRG neurons, as well as the length of afferent axons regenerated distal to the ulnar nerve crush. Furthermore, treatment with the CXCR4 inhibitor decreased levels of activated Signal Transducer and Activator of Transcription 3 (STAT3), a critical transforming factor in the neuronal regeneration program. Administration of IL-6 increased CXCR4 levels, whereas the JAK2-dependent STAT3 phosphorylation inhibitor (AG490) conversely decreased CXCR4 levels. This indicates a link between the CXCL12/CXCR4 signaling axis and IL-6-induced activation of STAT3 in the sciatic nerve injury-induced pro-regenerative state of cervical DRG neurons. The role of CXCR4 signaling in the axon-promoting state of DRG neurons was confirmed through in vitro cultivation of primary sensory neurons in a medium supplemented with CXCL12, with or without AMD3100. The potential involvement of conditioned cervical DRG neurons in the induction of neuropathic pain is discussed.
- MeSH
- benzylaminy MeSH
- chemokin CXCL12 * metabolismus MeSH
- cyklamy farmakologie MeSH
- heterocyklické sloučeniny farmakologie MeSH
- interleukin-6 metabolismus MeSH
- krysa rodu rattus MeSH
- nemoci sedacího nervu metabolismus MeSH
- nervové receptory * metabolismus MeSH
- nervus ischiadicus * zranění metabolismus MeSH
- potkani Sprague-Dawley MeSH
- receptory CXCR4 * metabolismus MeSH
- regenerace nervu * MeSH
- signální transdukce * MeSH
- spinální ganglia * metabolismus MeSH
- transkripční faktor STAT3 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This research investigated the effects of different hemodialysis modalities combined with low-calcium dialysate (LCD) on mineral metabolism and vascular calcification (VC) in maintenance hemodialysis (MHD) patients with chronic kidney disease (CKD). METHODS: General data were collected from 192 cases of MHD patients, who were divided into 4 groups according to the randomized numerical table. Each group was given LCD treatment, and conventional hemodialysis (HD), high-flux HD (HFHD), hemodiafiltration (HDF), and HD + hemoperfusion (HP) were performed, respectively. The patients were dialyzed 3 times per week for 4 h each time, and each group was treated for 6 months. Fasting venous blood was collected. Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitive C-reactive protein (hs-CRP) levels were measured by ELISA, calcium (Ca2+), phosphorus (P), Ca2+-P product, serum creatinine (SCr), blood urea nitrogen (BUN), β2 microglobulin (β2-MG), and intact parathyroid hormone (iPTH) were measured by chemiluminescence immunoassay, serum alkaline phosphatase (ALP) was determined by turbidimetric assay, and 25-hydroxyvitamin D (25(OH)D) was measured by autoradiographic immunoassay. To assess the extent of calcification in the iliac artery and abdominal aorta, a multilayer spiral CT device was employed for abdominal scans. RESULTS: Serum IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP levels decreased, while 25(OH)D levels increased in the four groups after treatment. The most pronounced effect on the reduction of IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP was in the HD + HP group, followed by the HDF and HFHD groups, and then by the HD group. The rate of VC in the HDF, HFHD, and HD + HP groups was lower than that in the HD group, and the rate in the HD + HP group was lower than that in the HDF and HFHD groups. CONCLUSION: The combination of HD + HP and LCD in treating CKD with MHD is effective, evidently rectifying disruptions in serum Ca2+ and P metabolism, enhancing kidney function, lessening the body's inflammatory response, and lessening VC.
- MeSH
- C-reaktivní protein metabolismus analýza MeSH
- chronická renální insuficience * terapie krev komplikace metabolismus MeSH
- dialýza ledvin * škodlivé účinky MeSH
- dialyzační roztoky farmakologie MeSH
- dospělí MeSH
- fosfor krev MeSH
- interleukin-6 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- minerály metabolismus krev MeSH
- parathormon krev MeSH
- senioři MeSH
- TNF-alfa krev MeSH
- vápník * krev metabolismus MeSH
- vaskulární kalcifikace * krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: By exposing mice carrying a deletion of NADPH oxidase isoform 4, NOX4, specifically in pancreatic β cells (βNOX4-/-) to nutrient excess stimulated by a high-fat diet (HFD), this study aimed to elucidate the role of β-cell redox status in the development of meta-inflammation within the diabetic phenotype. METHODS: The authors performed basic phenotyping of βNOX4-/- mice on HFD involving insulin and glycemic analyses, histochemistry of adipocytes, indirect calorimetry, and cytokine analyses. To characterize local inflammation, the study used caspase-1 activity assay, interleukin-1β immunochemistry, and real-time polymerase chain reaction during coculturing of β cells with macrophages. RESULTS: The phenotype of βNOX4-/- mice on HFD was not associated with hyperinsulinemia and hyperglycemia but showed accumulation of excessive lipids in epididymal fat and β cells. Surprisingly, mice showed significantly reduced systemic inflammation. Decreased interleukin-1β protein levels and downregulated NLRP3-inflammasome activity were observed on chronic glucose overload in βNOX4-/- isolated islets and NOX4-silenced INS1-E cells resulting in attenuated proinflammatory polarization of macrophages/monocytes in vitro and in situ and reduced local islet inflammation. CONCLUSIONS: Experimental evidence suggests that NOX4 pro-oxidant activity in β cells is involved in NLRP3-inflammasome activation during chronic nutrient overload and participates in local inflammatory signaling and perhaps toward peripheral tissues, contributing to a diabetic inflammatory phenotype.
